HK1090033B - Benzoazolypiperazine derivatives having vr1 antagonist activity - Google Patents

Description

Benzoxazole piperazine derivatives having VR1 antagonist activity

This application claims U.S. provisional application No. 60/435,917 (filed 12/24/2002); U.S. provisional application No. 60/459,626 (filed on 3/4/2003); and U.S. provisional application No. 60/473,856 (filed 5/29/2003), all of which are incorporated herein by reference in their entirety.

1. Field of the invention

The present invention relates to benzoxazole piperazine (benzoazollpiperazine) compounds, compositions comprising benzoxazole piperazine compounds, and methods for treating or preventing pain, Urinary Incontinence (UI), ulcers, Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), addiction, parkinson's disease, parkinson's syndrome, anxiety, epilepsy, stroke, seizures, pruritis, psychosis, cognitive disorders, memory deficits, restricted brain function, huntington's chorea, Amyotrophic Lateral Sclerosis (ALS), dementia, retinopathy, muscle spasms, migraine, vomiting, dyskinesia, or depression comprising administering an effective amount of a benzoxazole piperazine compound to an animal in need thereof.

2. Background of the invention

Pain is the most common symptom of patient medical questioning. Pain may be acute or chronic. While acute Pain is generally self-limiting, chronic Pain persists for 3 months or more and can lead to significant changes in the patient's personality, lifestyle, functional capacity, and overall quality of life (k.m. foley, Pain, in occidental Textbook of Medicine)100-107(j.c. bennett and f.plum eds., 20 th edition 1996)).

The traditional management of pain has been the administration of non-opioid analgesics, such as aspirin, choline magnesium trisalicylate, acetaminophen, ibuprofen, fenoprofen, diflunisal, and naproxen, or opioid analgesics, including morphine, hydromorphone, methadone, levorphanol, fentanyl, oxycodone, and oxymorphone. The same goes for (Id).

UI is uncontrolled urination, usually caused by instability of the bladder detrusor muscle. The UI affects people of all ages and physical fitness levels, and people living in communities both inside and outside the healthcare facility can be affected. Currently, UI afflicts 15-30% of the elderly living at home, one third of those living in emergency care facilities and at least one half of those living in long-term care facilities (r.m. research, Lancet) 346: 94(1995)). Those with UI are also susceptible to urinary tract infections, pressure ulcers, perineal rashes and urosepsis. Psychosocial aspects, UI is associated with embarrassment, social discrimination, depression, and risk of becoming accustomed (institutional) (Herzo et al, annu.9: 74(1989)). On the economic side, the cost of treating UI is high; in the united states alone, the medical costs associated with treating UI exceed $ 150 billion per year.

Physiological bladder contractions are mostly caused by acetylcholine-induced stimulation of muscarinic receptor sites behind the upper (neural) segment of the bladder smooth muscle. Treatment for UI including administration help controlA medicament for suppressing bladder detrusor overactivity having bladder relaxant properties. For example, anticholinergics (such as propantheline bromide and glycopyrrolate) and combinations with smooth muscle relaxants (such as the combination of racemic oxybutynin and a bicyclic amine or an anticholinergic) have been used to treat UI (see, e.g., a.j.wein, urol.22: 557-577 (1995); levin et al, J Urol.128: 396-398 (1982); cooke et al, s.afr.med.j.63: 3 (1983); R.K. Mirakhur et al, Anaesthesia38: 1195-1204(1983)). However, these drugs are not effective in all patients whose bladder contractions are not controlled. Therapy with the administration of anticholinergics represents the mainstay of such treatment.

However, none of the currently available drugs for UI treatment has been able to achieve complete success in all types of UI patients, nor has it been able to produce significant side effects upon treatment. For example, drowsiness, dry mouth, constipation, blurred vision, headaches, tachycardia, and arrhythmia associated with the anticholinergic activity of traditional anti-UI drugs can occur frequently and adversely affect patient compliance. However, despite the occurrence of unwanted anticholinergic effects in many patients, anticholinergic drugs are still currently prescribed for patients with UI. The Merck Manual of Medical Information 631 and 634(R. Berkow eds., 1997).

Ulcers are sores that occur in the inner layers of the digestive tract that have been eroded by stomach acid or digestive juices. These sores are typically well-defined, circular or oval lesions that occur primarily in the stomach and duodenum. Approximately 1 out of 10 people develop ulcers. The development of ulcers is the result of acid secretion factors, also known as "erosive factors" such as gastric acid, pepsin and helicobacter pylori infection and local mucosal protective factors such as the secretory imbalance of bicarbonate, mucus and prostaglandins.

Treatment of ulcers typically involves reducing or inhibiting erosive factors. For example, antacids such as aluminum hydroxide, magnesium hydroxide, sodium bicarbonate, and calcium bicarbonate can be used to neutralize gastric acid. However, antacids can cause alkalosis, leading to nausea, headache, and weakness. Antacids can also interfere with the absorption of other drugs into the bloodstream and cause diarrhea.

H₂Antagonists, such as cimetidine, ranitidine, famotidine and nizatidine, have also been used to treat ulcers. In the stomach and duodenum, H₂Antagonists by reducing histamine and other H₂The agonist induces secretion of gastric acid and digestive enzymes to promote ulcer healing. However, H₂Antagonists can cause breast enlargement and impotence in men, mental changes (especially in the elderly), headache, dizziness, nausea, myalgia, diarrhea, rash, and fever.

H⁺，K⁺Adenosine triphosphate inhibitors (e.g. omeprazole and lansoprazole) may also be used to treat ulcers. H⁺，K⁺Inhibitors of atpase inhibit the production of enzymes used for gastric acid secretion. And H⁺，K⁺Adenosine triphosphate inhibitor-related side effects include nausea, diarrhea, abdominal cramps, headache, dizziness, somnolence, rash and transient elevation of plasma transaminase activity.

Sucralfate is also used to treat ulcers. Sucralfate adheres to epithelial cells and is believed to form a protective layer at the base of the ulcer to promote healing. However, sucralfate can cause constipation, dry mouth and interfere with the absorption of other drugs.

When helicobacter pylori is a potential cause of ulcers, antibiotic therapy is applied. Antibiotic therapy is often used in combination with bismuth compounds (e.g., bismuth subsalicylate and colloidal bismuth citrate). Bismuth compounds are believed to increase mucus and HCO₃ ^-The secretion of the active ingredient, the inhibition of the activity of pepsin, and the action of an antibacterial agent such as anti-helicobacter pylori. However, ingestion of bismuth compounds can result in plasma Bi⁺³The concentration rises and may interfere with the absorption of other drugs.

Prostaglandin analogs, such as misoprostol, which inhibit acid secretion and stimulate mucus and bicarbonate secretion, are also used to treat ulcers, particularly in patients who require nonsteroidal anti-inflammatory drugs. However, effective oral doses of prostaglandin analogs can result in diarrhea and abdominal cramps. In addition, some prostaglandin analogs can promote abortion.

Carbenoxolone, a mineralocorticoid, can also be used to treat ulcers. Carbenoxolone appears to alter the composition and quantity of mucus, thereby enhancing the mucosal barrier. However carbenoxolone can cause Na ⁺And fluid retention, hypertension, hypokalemia, and impaired glucose tolerance.

Muscarinic cholinergic antagonists such as pirenzepine hydrochloride and telenzepine may also be used to reduce acid secretion and treat ulcers. Side effects of muscarinic cholinergic antagonists include dry mouth, blurred vision, and constipation. The Merck Manual of Medical Information 496-.

Inflammatory bowel disease is a chronic disease of intestinal inflammation, often resulting in recurrent abdominal cramps and diarrhea. Two types of inflammatory bowel disease are Crohn's disease and ulcerative colitis.

Crohn's disease, which may include Crohn's disease, granulomatous ileitis, and ileocolitis, is a chronic inflammation of the intestinal wall. Crohn's disease occurs with equal chance in both sexes and is more common in eastern european jewish. Most cases of Crohn's disease begin before the age of 30 and mostly between the ages of 14 and 24. The disease is characterized by affecting the entire layer of the intestinal wall. The disease usually affects the lowest segment of the small intestine (ileum) and the large intestine, but can occur anywhere in the digestive tract.

Early symptoms of Crohn's disease are chronic diarrhea, cramping abdominal pain, fever, anorexia, and weight loss. Complications associated with Crohn's disease include the occurrence of ileus, abnormal connective pathways (fistulas) and abscesses. In patients with Crohn's disease, the risk of developing large bowel cancer is increased. Typically, Crohn's disease is associated with other diseases such as cholelithiasis, malabsorption, amyloidosis, arthritis, episcleritis, aphthous stomatitis, erythema nodosum, pyoderma gangrenosum, ankylosing spondylitis, sacroiliitis, uveitis, and primary sclerosing cholangitis. At present, no method for radically treating Crohn's disease is found.

Cramps and diarrhea are side effects associated with Crohn's disease and can be alleviated by anticholinergics, diphenoxylate, loperamide, tincture of deodorized opium, or codeine. Such drugs are usually taken orally before meals.

Broad spectrum antibiotics are often used to treat the symptoms of Crohn's disease. The antibiotic metronidazole is often used when the disease affects the large intestine or causes perianal abscesses and fistulas. However, chronic metronidazole can damage nerves, resulting in tingling sensations in the arms and legs. Sulfasalazine and chemically related drugs can arrest mild inflammation, particularly in the large intestine. However, these drugs are less effective against sudden, acute episodes (flare-ups). Corticosteroids (such as prednisone) reduce fever and diarrhea, and relieve abdominal pain and tenderness. However, long-term corticosteroid therapy often results in severe side effects such as high blood glucose levels, increased risk of infection, osteoporosis, water retention, and skin fragility. Drugs such as azathioprine and penicillamine can suppress the immune system and are often effective in patients with Crohn's disease who are unresponsive to other drugs. However, these drugs typically take 3 to 6 months to produce a benefit, and can cause serious side effects such as allergy, pancreatitis, and decreased white blood cell count.

When Crohn's disease causes ileus or when abscesses or fistulas do not heal, surgery may be necessary to excise the site of the intestinal lesion. However, surgery does not cure the disease and inflammation tends to recur at sites of intestinal rejoining. Most cases require secondary surgery. The Merck Manual of medical Information 528-530(R. Berkow eds., 1997).

Ulcerative colitis is a chronic disease in which the large intestine of a patient becomes inflamed and ulcerated, resulting in the onset of bloody diarrhea, abdominal cramps, and fever. Ulcerative colitis usually begins between the ages of 15 and 30, however, the initial onset for a small group of people is between the ages of 50 and 70. Unlike Crohn's disease, ulcerative colitis never affects the small intestine and does not affect the entire layer of the intestine. The disease usually begins in the rectum and sigmoid colon and eventually spreads to part or all of the large intestine. The etiology of ulcerative colitis is currently unclear.

The therapeutic guidelines for ulcerative colitis are to control inflammation, alleviate symptoms and replenish lost fluids and nutrients. Mild diarrhea is treated with anticholinergics and small doses of fenoxate or loperamide. For more severe diarrhea, a larger dose of fenoxate or loperamide or tincture of deodorized opium or codeine is used. Sulfasalazine, olsalazine, prednisone or mesalazine may be used to reduce inflammation. Azathioprine and mercaptopurine have been used to treat patients with ulcerative colitis who would otherwise require chronic steroid administration. Patients with severe ulcerative colitis need hospitalization and intravenous administration of corticosteroids. Patients with severe rectal bleeding may require blood transfusion and intravenous fluid infusion. If toxic colitis develops and the treatment is ineffective, surgical resection of the large intestine may be necessary. Non-emergency surgery may be feasible if diagnosis of cancer, finding a precancerous lesion, or a persistent chronic condition otherwise results in patient disability, or relies on high doses of corticosteroids. Ulcerative colitis can be cured completely by complete excision of the large intestine and rectum. The Merck Manual of medical information 530-.

Irritable bowel syndrome is a motility disorder of the entire gastrointestinal tract leading to abdominal pain, constipation and/or diarrhea. Allergic large bowel syndrome affects women three times as much as men. In patients with irritable bowel syndrome, irritation such as stress, diet, drugs, hormones or irritants can cause abnormal contraction of the gastrointestinal tract. During the onset of irritable bowel syndrome, contractions of the gastrointestinal tract become stronger and more frequent, causing food and feces to pass quickly through the small intestine, often causing diarrhea. Colic is caused by a strong contraction of the large intestine and an increase in the sensitivity of pain receptors in the large intestine.

There are two main types of irritable bowel syndrome. The first is the spastic colon type, usually triggered by food intake, and often produces periodic painful constipation and diarrhea. Mucus is common in feces. Pain can be recurrent episodes of persistent dull soreness or cramping, often in the lower abdomen. Patients with irritable bowel syndrome of the spastic colon type may also exhibit bloating, anal venting, nausea, headache, weakness, depression, anxiety and difficulty concentrating. The second group of irritable bowel syndromes usually causes painless diarrhea or constipation. Diarrhea can be sudden and extremely urgent. Diarrhea often occurs shortly after a meal and can sometimes occur immediately after waking.

Treatment of irritable bowel syndrome is generally associated with improving the diet of patients with allergic bowel syndrome. Allergic large bowel syndrome patients are generally advised to avoid legumes, cabbage, sorbitol and fructose. A low-fat, high-fiber diet may be helpful for some patients with irritable bowel syndrome. Regular physical exercise may also help to keep the gastrointestinal tract functioning properly. Drugs that reduce gastrointestinal function (such as pullulan) are generally not effective in treating irritable bowel syndrome. Antidiarrheal drugs (such as diphenoxylate and loperamide) are helpful in diarrhea. The Merck Manual of medical Information 525-.

Many drugs can cause physical and/or psychological addiction. The most well known types of these drugs include opiates, such as heroin, opium and morphine; sympathomimetics including cocaine and amphetamine; sedative hypnotics including ethanol, diazepam and barbiturates; and nicotine, which acts similarly to opioids and sympathomimetics. Drug addiction is characterized by a craving or compulsive urge to take the drug and the inability to restrict its intake. In addition, drug dependence is associated with drug tolerance (i.e., a decrease in drug efficacy following repeated dosing) and addictive brain syndrome (i.e., physical and behavioral symptoms that occur without drug administration). Sensitization occurs if repeated administration of a drug results in an enhanced response to each dose. Drug tolerance, sensitization and withdrawal symptoms are phenomena that have been shown to cause changes in the central nervous system with continued use of the drug. This change can drive addicted individuals to continue to use the drug regardless of serious social, legal, physical and/or occupational consequences. (see, e.g., U.S. Pat. No. 6,109,269 to Rise et al).

Certain agents have been used to treat addictive disorders. U.S. Pat. No. 5,556,838 to Mayer et al discloses the use of nontoxic NMDA-blocking agents in combination with an addictive substance to prevent the development of drug resistance or withdrawal symptoms. U.S. Pat. No. 5,574,052 to Rose et al discloses the use of an antagonist in combination with an addictive substance to partially block the pharmacological effect of the substance. U.S. Pat. No. 5,075,341 to Mendelson et al discloses the treatment of cocaine and opiate addiction with a mixed opiate agonist/antagonist. U.S. patent No. 5,232,934 to Downs discloses the use of 3-phenoxypyridines for treating addictive disorders. U.S. patent nos. 5,039,680 and 5,198,459 to imparato et al disclose the treatment of chemical addiction with a 5-hydroxytryptamine antagonist. U.S. patent No. 5,556,837 to Nestler et al discloses infusion of BDNF or NT-4 growth factors to inhibit or reverse the changes in neuro-adaptive responses associated with behavioral changes in an addictive individual. U.S. patent No. 5,762,925 to Sagan discloses the implantation of encapsulated adrenal medullary cells into the central nervous system of an animal to inhibit the development of opioid intolerance. U.S. Pat. No. 6,204,284 to Beer et al discloses racemic (±) -1- (3, 4-dichlorophenyl) -3-azabicyclo [3.1.0] hexane for preventing or alleviating withdrawal syndromes from drug addiction and for treating chemical dependence.

Parkinson's disease is a clinical syndrome involving bradykinesia (slowness and lack of movement), muscle stiffness, resting tremor (usually reduced when exercising at will), and postural balance deficits leading to gait disturbances and falls. Parkinson's disease is characterized by The loss of pigment from The substantia nigra pars compacta, dopaminergic neurons of The substantia nigra column, and The appearance of intracellular inclusions known as Lewy bodies (Goodman and Gillman's The Pharmaceutical basic of therapeutics 506 (9 th edition, 1996)). Without treatment, Parkinson's disease will progress to a stiff immobility state and the patient will be unable to care for themselves. Death is often caused by immotile complications, including aspiration pneumonia or pulmonary embolism. Commonly used drugs for the treatment of parkinson's disease include carbidopa/levodopa, pergolide, bromocriptine, selegiline, amantadine and benzhexol hydrochloride. However, there is still a need for drugs that are useful for the treatment of parkinson's disease and that have a better therapeutic profile.

Anxiety is a fear, uneasiness or fear of imminent danger, often accompanied by restlessness, tension, tachycardia and dyspnea. Other symptoms often associated with anxiety include depression, particularly with dysthymic disorder (chronic "neurogenic" depression), panic disorder, agoraphobia and other specific phobias, eating disorders and various personality disorders. Anxiety disorders are not usually associated with a diagnostically clear treatable primary event. However, if a primary condition is found, it is desirable to treat anxiety disorders at the same time as the primary condition.

Currently, diazepam is the most commonly used anxiolytic for general anxiety disorders. However, diazepam carries the risk of developing impairment leading to cognitive and skilled motor functions, which, especially in the elderly, can eventually lead to confusion, delrium and falls and fractures. Sedatives are also commonly used to treat anxiety disorders. Azaperones (azapirones), such as buspirone, are also used to treat moderate anxiety disorders. Azaperone, however, is less effective in treating anxiety disorders with a severity of panic attacks.

Epilepsy is a disorder characterized by a tendency to have recurrent seizures. Etiology usually involves lesions of some part of the cortex such as tumors; developmental malformation; or injury from trauma or shock. In some cases, the etiology is genetic. An epileptic seizure may be triggered by repeated sounds, flashing lights, video games, or contact with certain parts of the body. Typically, antiepileptic drugs are used to treat epilepsy. In cases of epilepsy, such as epilepsy, where antiepileptic drugs are ineffective and the defect in the brain is located in a small area of the brain, surgical removal of this small area of the brain may be helpful in reducing seizures. For those patients with seizures of several origins or with seizures spreading rapidly to all parts of the brain, surgical removal of nerve fibers connecting the two parts of the brain may be helpful.

Examples of drugs for the treatment of epilepsy and seizures include: carbamazepine, ethosuximide, gabapentin, lamotrigine, phenobarbital, phenytoin, primidone, valproic acid, trimethadione, diazepam, gamma-vinyl GABA, acetazolamide and felbamate. However, antiepileptics can have side effects, such as drowsiness; hyperexcitability; hallucinations; attention cannot be focused; central and peripheral nervous system toxicities such as nystagmus, ataxia, diplopia and vertigo; gingival hyperplasia; gastrointestinal disorders such as nausea, vomiting, epigastric pain and anorexia; endocrine effects such as inhibition of antidiuretic hormone, hyperglycemia, diabetes, osteomalacia; and hypersensitivity reactions such as scarlet fever-like rashes, measles-like rashes, Stevens-Johnson syndrome, systemic lupus erythematosus and hepatic necrosis; and hematological responses such as red cell dysplasia, agranulocytosis, thrombocytopenia, aplastic anemia, and megaloblastic anemia. The Merck Manual of Medical Information 345-350(R. Berkow eds., 1997).

Seizures are the result of abnormal discharges in the brain. The discharge may involve a small area of the brain and cause the patient to notice only a strange taste or smell, or may involve a large area of the brain and cause seizures, i.e. seizures that cause twitching and cramping of the muscles of the body. Grand mal seizures can also cause transient seizures that alter consciousness as well as cause loss of consciousness, muscle control, and urinary control. Prior to a seizure, there is often a aura, i.e., an unusually smelling taste or sight or a strong sense of the onset of the seizure. A typical seizure lasts about 2 to 5 minutes. After the end of a seizure, the patient may have headache, muscle pain, unusual sensations, confusion, and extreme fatigue (post-seizure state). Patients typically have no memory of what happens during a seizure.

Stroke or cerebrovascular accident is the death of brain tissue (cerebral infarction) due to cerebral ischemia and hypoxia. Stroke may be ischemic or hemorrhagic. In ischemic stroke, blood flow to the brain is interrupted by atherosclerosis or blood clots occluding the blood vessels. In a hemorrhagic stroke, blood vessels rupture preventing normal blood flow and causing blood to leak to and damage an area of the brain. Most strokes develop rapidly and within minutes lead to brain damage. In some cases, however, stroke may continue to worsen for hours or days. The symptoms of stroke vary from one affected brain region to another. Symptoms include paresthesia or loss of one upper or lower limb or one body, weakness or paralysis of one upper or lower limb or one body, partial loss of vision or hearing, double vision, dizziness, slurred speech, difficulty in finding words or expression, inability to recognize body parts, unusual movement, urinary incontinence, balance disorders and falls, and syncope. These symptoms can be persistent and can be accompanied by coma or stupor. Stroke can lead to cerebral edema or swelling, further damaging brain tissue. For stroke patients, enhanced rehabilitation may help recovery from disability caused by brain tissue damage. Other parts of the brain are rehabilitated and trained to undertake tasks previously performed by the injured part.

Examples of drugs for treating stroke include anticoagulants (e.g., heparin), thrombolytic drugs (e.g., streptokinase or tissue plasminogen activator), and edema-alleviating drugs (e.g., mannitol or corticosteroids). The Merck Manual of Medical Information 352-355(R. Berkow eds., 1997).

Pruritus is an unpleasant sensation that causes scratching. The pruritus may be due to dry skin, scabies, dermatitis, atopic dermatitis, dermatitis herpetiformis, vulvar, anal itch, miliaria, insect bites, pediculosis, contact dermatitis, drug reactions, urticaria of pregnancy, psoriasis, lichen planus, lichen simplex chronicus, exfoliative dermatitis, folliculitis, bullous pemphigoid, and cellodermatitis. Conventionally, pruritus is treated by phototherapy with ultraviolet B or PUVA or therapeutic drugs such as naltrexone, nalmefene, danazol, tricyclic drugs and antidepressants.

Selective antagonists of the metabotropic (metabotropic) glutamate receptor 5 ("mGluR 5") have been shown to exert analgesic activity in vivo animal models (K.Walker et al, Neuropharmacology 40: 1-9(2000) and A.Dogrul et al, Neuroscience Letters, 292 (2): 115-.

Selective antagonists of the mGluR5 receptor have also been shown to exert anxiolytic and antidepressant activity in vivo animal models (E.Tarrc zynska et al, Br.J.Pharmacol.132 (7): 1423-1430(2001) and P.J.M.Will et al, Trends in Pharmacological Sciences22 (7): 331-37 (2001)).

Selective antagonists of the mGluR5 receptor have also been shown to exert anti-Parkinson activity in vivo (K.J. Ossowska et al, Neuropharmacology 41 (4): 413-20 (2001)) and P.J. M.Will et al, Trends in pharmaceutical Sciences22 (7): 331-37 (2001)).

Selective antagonists of the mGluR5 receptor have also been shown to exert anti-addictive activity in vivo (C.Chiamulera et al, Nature Neuroscience 4 (9): 873-74 (2001)).

U.S. patent No. 6,150,129 to Cook et al describes a class of bis-nitrogen heterocycles useful as antibiotics.

U.S. patent No. 5,529,998 to Habich et al describes a class of benzoxazolyl-and benzimidazolyl oxazolidinones useful as antibacterial agents.

International publication No. WO 01/57008 describes a class of 2-benzimidazolyl urea derivatives useful as serine/threonine and tyrosine kinase inhibitors.

International publication No. WO 02/08221 describes arylpiperazine compounds useful in the treatment of chronic and acute painful conditions, itch and urinary incontinence.

International publication No. WO 99/37304 describes substituted oxaziridinyl compounds for inhibiting factor Xa.

International publication No. WO 00/59510 describes aminopyrimidines useful as sorbitol dehydrogenase inhibitors.

Japanese patent application No. 11-199573 to Kiyoshi et al describes benzothiazole derivatives which are agonists of the neuronal 5HT3 receptor of the enteric nervous system and are useful in the treatment of digestive disorders and pancreatic insufficiency.

German patent application No. 19934799 to Rainer et al describes a chiral-purified liquid crystal mixture containing compounds with 2 linked (hetero) aromatic rings or compounds with 3 linked (hetero) aromatic rings.

chu-Moyer et al, in j.med.chez.45: 511-528(2002) describe heterocyclic-substituted piperazino-pyrimidines useful as sorbitol dehydrogenase inhibitors.

Khardse et al, in bull. haff. instt.1 (3): 27-32(1975) describe 2- (N) as anthelmintics⁴-substituted-N¹-piperazinyl) pyrido (3, 2-d) thiazole and 5-nitro-2- (N)⁴-substituted-N¹-piperazinyl) benzothiazole.

However, there remains a clear need in the art for new drugs for the treatment or prevention of pain, UI, ulcers, IBD, IBS, addiction, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, seizures, pruritus, psychosis, cognitive disorders, memory deficits, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, muscle spasm, migraine, emesis, movement disorders or depression.

Citation of any reference in the second section of this application shall not be construed as an admission that such reference is prior art to the present application.

3. Brief description of the invention

The present invention includes compounds having formula (Ia):

and pharmaceutically acceptable salts thereof, wherein

Ar₁Is composed of

A is

R₁is-Cl, -Br, -I, - (C)₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl,-(C₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

each R₃Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R ₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

R₄is-H or- (C)₁-C₆) An alkyl group;

each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₉Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, -C (halo)₃-CH (halo)₂、-CH₂(halo), -OC (halo)₃-OCH (halo)₂、-OCH₂(halo), -CN, -OH, -halo, -N₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each-halo is-F, -Cl, -Br or-I;

n is an integer of 0 to 3;

p is an integer of 0 to 2;

m is 0 or 1; and

x is 0 or 1.

The present invention includes compounds having the formula (Ib):

and pharmaceutically acceptable salts thereof, wherein

Ar₁Is composed of

A is

R₁is-H, -halo, - (C) ₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

each R₃Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

R₄is-H or- (C)₁-C₆) An alkyl group;

each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₉Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, -C (halo)₃-CH (halo)₂、-CH₂(halo), -OC (halo)₃-OCH (halo)₂、-OCH₂(halo), -CN, -OH, -halo, -N₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each-halo is-F, -Cl, -Br or-I;

p is an integer of 0 to 2;

m is 0 or 1; and

x is 0 or 1.

The invention includes compounds having formula (IIa):

and pharmaceutically acceptable salts thereof, wherein

Ar₁Is composed of

R₁is-Cl, -Br, -I, - (C)₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C) ₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

each R₃Independent of each otherComprises the following steps:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C) ₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₉Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, -C (halo)₃-CH (halo)₂、-CH₂(halo), -OC (halo)₃-OCH (halo)₂、-OCH₂(halo), -CN, -OH, -halo, -N₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

R₁₀is-H or- (C)₁-C₄) An alkyl group;

each-halo is-F, -Cl, -Br or-I;

n is an integer of 0 to 3;

p is an integer of 0 to 2; and

m is 0 or 1.

The invention includes compounds having the formula (IIb):

and pharmaceutically acceptable salts thereof, wherein

Ar₁Is composed of

A is

R₁is-H, -halo, - (C)₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R ₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

each R₃Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

R₄is-H or- (C)₁-C₆) An alkyl group;

each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C) ₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₉Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, -C (halo)₃-CH (halo)₂、-CH₂(halo), -OC (halo)₃-OCH (halo)₂、-OCH₂(halo), -CN, -OH, -halo, -N₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

R₁₀is-H or- (C)₁-C₄) An alkyl group;

each-halo is-F, -Cl, -Br or-I;

p is an integer of 0 to 2;

m is 0 or 1; and

x is 0 or 1.

The invention includes compounds having formula (IIIa):

and pharmaceutically acceptable salts thereof, wherein

Ar₁Is composed of

A is

R₁is-Cl, -Br, -I, - (C)₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted orFrom one or more R ₆Substituted by groups;

each R₃Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

R₄is-H or- (C)₁-C₆) An alkyl group;

each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₉Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C) ₅-C₈) Cycloalkenyl, -phenyl, -C (halo)₃-CH (halo)₂、-CH₂(halo), -OC (halo)₃-OCH (halo)₂、-OCH₂(halo), -CN, -OH, -halo, -N₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each-halo is-F, -Cl, -Br or-I;

n is an integer of 0 to 3;

p is an integer of 0 to 2;

m is 0 or 1; and

x is 0 or 1.

The invention includes compounds having formula (IIIb):

and pharmaceutically acceptable salts thereof, wherein

Ar₁Is composed of

A is

R₁is-H, -halo, - (C)₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl or- (7-to 10-membered) bicyclic heterocycle each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl or- (C)₁₄) Aryl radical, whereinEach of which is unsubstituted or is substituted by one or more R₆Substituted by groups;

each R₃Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C) ₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

R₄is-H or- (C)₁-C₆) An alkyl group;

each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo)) -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₉Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, -C (halo)₃-CH (halo)₂、-CH₂(halo), -OC (halo)₃-OCH (halo)₂、-OCH₂(halo), -CN, -OH, -halo, -N₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each-halo is-F, -Cl, -Br or-I;

p is an integer of 0 to 2;

m is 0 or 1; and

x is 0 or 1.

The invention also includes compounds having formula (IVa):

and pharmaceutically acceptable salts thereof, wherein

Ar₁Is composed of

Ar₂Is composed of

R₁Is-halo, - (C)₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroarylEach of which is unsubstituted or substituted by one or more R₆Substituted by groups;

R₃is-H or-CH₃：

Each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C) ₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₉Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, -C(halo)₃-CH (halo)₂、-CH₂(halo), -OC (halo)₃-OCH (halo)₂、-OCH₂(halo), -CN, -OH, -halo, -N₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each-halo is-F, -Cl, -Br or-I;

n is an integer of 0 to 3; and

p is an integer of 0 to 2.

The invention also includes compounds having formula (IVb):

and pharmaceutically acceptable salts thereof, wherein

Ar₁Is composed of

Ar₂Is composed of

A is

R₁Is-halo, - (C)₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R ₆Substituted by groups;

R₃is-CH₃；

R₄is-H or- (C)₁-C₆) An alkyl group;

each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-O C(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₉Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, -C (halo)₃-CH (halo)₂、-CH₂(halo), -OC (halo)₃-OCH (halo)₂、-OCH₂(halo), -CN, -OH, -halo, -N₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each-halo is-F, -Cl, -Br or-I;

n is an integer of 0 to 3;

p is an integer of 0 to 2; and

x is 0 or 1.

The invention also includes compounds having formula (V):

and pharmaceutically acceptable salts thereof, wherein

Ar₁Is composed of

Ar₂Is composed of

R₁Is-halo, - (C)₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH ₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

R₃is-H or-CH₃；

Each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₇Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, -C (halo)₃-CH (halo)₂、-CH₂(halo), -OC (halo)₃-OCH (halo)₂、-OCH₂(halo), -CN, -OH, -halo, -N ₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each-halo is-F, -Cl, -Br or-I;

n is an integer of 0 to 3; and

p is an integer of 0 to 2.

A compound of formula (Ia), (Ib), (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb) and (V) or a pharmaceutically acceptable salt thereof (a "benzoxazole piperazine compound") for use in treating or preventing pain, UI, an ulcer, IBD, IBS, an addiction, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, emesis, a movement disorder or depression in an animal.

The invention also relates to a composition comprising an effective amount of the benzoxazole piperazine compound and a pharmaceutically acceptable carrier or excipient. The composition is useful for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal.

The invention also relates to a method of treating pain, Ul, ulcers, IBD, IBS, addiction, parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, seizures, pruritis, psychosis, cognitive disorders, memory deficits, restricted brain function, huntington's chorea, ALS, dementia, retinopathy, muscle spasm, migraine, emesis, dyskinesia or depression comprising administering to an animal in need thereof an effective amount of a benzoxazole piperazine compound.

The invention also relates to a method of preventing pain, UI, an ulcer, IBD, IBS, an addiction, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression, comprising administering to an animal in need thereof an effective amount of a benzoxazole piperazine compound.

The invention still further relates to a method of inhibiting Vanilloid receptor 1 ("VR 1") function in a cell, the method comprising contacting a cell capable of expressing VR1 with an effective amount of a benzoxazole piperazine compound.

The invention is still further directed to a method of inhibiting mGluR5 function in a cell, the method comprising contacting a cell capable of expressing mGluR5 with an effective amount of a benzoxazole piperazine compound.

The invention still further relates to a method of inhibiting metabotropic glutamate receptor 1 ("mGluR 1") function in a cell, comprising contacting a cell capable of expressing mGluR1 with an effective amount of a benzoxazole piperazine compound.

The present invention is still further directed to a process for preparing a composition comprising the step of admixing a benzoxazole piperazine compound and a pharmaceutically acceptable carrier or excipient.

The invention still further relates to a kit comprising a container containing an effective amount of a benzoxazole piperazine compound.

The invention still further relates to a compound selected from the group consisting of

And pharmaceutically acceptable salts thereof.

The invention still further relates to a compound selected from the group consisting of

And pharmaceutically acceptable salts thereof.

The invention still further relates to a compound selected from the group consisting of the following and pharmaceutically acceptable salts thereof.

The present invention may be understood more fully by reference to the detailed description and the exemplary examples which follow, which are intended as illustrations of non-limiting embodiments of the invention.

4. Detailed description of the invention

4.1 Compounds of formula (Ia)

As mentioned above, the present invention includes compounds of formula (Ia)

And pharmaceutically acceptable salts thereof, wherein Ar₁、R₃、R₈、R₉A, x and m are as defined above for the compound of formula (Ia) for p-benzoxazolyl piperazine.

In one embodiment, Ar₁Is a pyridyl group.

In another embodiment, Ar₁Is a pyrimidinyl group.

In another embodiment, x is 1 and A is-C (O) -N (R)₄)-。

In another embodiment, x is 1 and A is-C (S) -N (R)₄)-。

In another embodiment, x is 0.

In another embodiment, n or p is 0.

In another embodiment, n or p is 1.

In another embodiment, m is 0.

In another embodiment, m is 1.

In another embodiment, R₄is-H.

In another embodiment, R₄Is- (C)₁-C₆) An alkyl group.

In another embodiment, Ar₁Is pyridyl, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, Ar₁Is pyridyl, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, Ar₁Is pyrimidinyl, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, Ar₁Is pyrimidinyl, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, R₁is-Cl.

In another embodiment, R ₁is-Br.

In another embodiment, R₁is-I.

In another embodiment, R₁Is- (C)₁-C₆) An alkyl group.

In another embodiment, R₁is-CH₃。

In another embodiment, R₁is-NO₂。

In another embodiment, R₁is-CN.

In another embodiment, R₁is-OH.

In another embodiment, R₁is-OCH₃。

In another embodiment, R₁is-NH₂。

In another embodiment, R₁is-C (halo)₃。

In another embodiment, R₁is-CH (halo)₂。

In anotherIn embodiments, R₁is-CH₂(halo).

In another embodiment, n and p are 1 and R₂Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, n and p are 1 and R₂Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅And (4) substituting the group.

In another embodiment, n and p are 1 and R₂Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R ₆Substituted by groups;

in another embodiment, m is 1 and R₃Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, m is 1 and R₃Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅And (4) substituting the group.

In another embodiment, m is 1 and R₃Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆And (4) substituting the group.

In another embodiment, R₈And R₉Each independently of the other being-H, -halo, - (C)₁-C₆) Alkyl, -O (C)₁-C₆) Alkyl, -C (halo)₃-CH (halo)₂or-CH₂(halo).

In another embodiment, R₈And R₉At least one of which is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉Is-halo. In another embodiment, R₁is-Cl. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₁is-Cl. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈Is-halo; and R₉is-H. In another embodiment, R₁is-Cl. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₁is-Cl. In another embodiment, R ₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-CF₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-CF₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r ₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-OCH₂CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-OCH₂CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H;and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈Is-halo; and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r ₁is-CH₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-CF₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-OCH₂CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-CF ₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈Is-halo; and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 1; a is-C (O)-N(R₄)-；R₄is-H; r₈is-H; and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-CF₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-OCH₂CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈Is a-tert-butyl group; and R₉is-H.

In another embodiment, n, p and m are 0; r ₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈Is a-tert-butyl group; and R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈Is a-tert-butyl group; and R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H; and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-CH₃(ii) a And R₉is-CH₃。

In another embodiment, n is 0, Ar₁Is-2- (3-nitropyridyl) -, m is 0, x is 0, and R₈And R₉is-H.

In another embodiment, n is 0, Ar₁Is-2- (3-chloropyridyl) -, x is 1, A is-C (S) -N (R)₄) -, m is 1, R₃is-CH₃，R₃To the linkage-C (SO) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₃The carbon atom to which the radicals are attached having the R configuration, R₈is-H, R₉is-CH₃。

In another embodiment, n and p are 0; m is 1; r ₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is I, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another implementationIn the scheme, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-H; and R₉Is-halo. In another embodiment, R₈is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈Is-halo; and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃Group attachmentHas the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R) ₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-H; and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And are connected withTo the linkage of-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-CH₃(ii) a And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-H; and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R ₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-CF₃(ii) a And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R) ₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-H; and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-OCH₂CH₃(ii) a And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH ₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In anotherIn embodiments, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R ₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In addition toIn one embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈Is a-tert-butyl group; and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r ₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈is-H; and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH ₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-H; and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R ₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-H; and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈Is-halo; and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈Is-halo; and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-H; and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-H; and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r ₁is-Cl; x is 0; r₄is-H; r₈is-CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-H; and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-H; and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-CF₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-CF₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-H; and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-H; and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-OCH₂CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-OCH₂CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 0; r₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r ₁is-CH₃(ii) a x is 0; r₄is-H; r₈is-H; and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 0; r₄is-H; r₈Is-halo; and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 0; r₄is-H; r₈is-H; and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 0; r₄is-H; r₈is-CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 0; r₄is-H; r₈is-H; and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 0; r₄is-H; r₈is-CF₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 0; r₄is-H; r₈is-H; and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0, R₁is-CH₃(ii) a x is 0; r₄is-H; r₈is-OCH₂CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r ₁is-CF₃(ii) a x is 0; r₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 0; r₄is-H; r₈is-H; and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 0; r₄is-H; r₈Is-halo; and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0, R₁is-CF₃(ii) a x is 0; r₄is-H; r₈is-H; and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 0; r₄is-H; r₈is-CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 0; r₄is-H; r₈is-H; and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 0; r₄is-H; r₈is-CF₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CF₃(ii) a x is 0; r₄is-H; r₈is-H; and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r ₁is-CF₃(ii) a x is 0; r₄is-H; r₈is-OCH₂CH₃(ii) a And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈Is a-tert-butyl group; and R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈Is a-tert-butyl group; and R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-H; and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-H; and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 0; r₄is-H; r₈Is a-tert-butyl group; and R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 0; r₄is-H; r₈is-H; and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0; r₁is-CH₃(ii) a x is 0; r₄is-H; r₈is-CH₃(ii) a And R₉is-CH₃。

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₈is-H; and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br.In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R ₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₈Is-halo; and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R ₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Radical (I)The attached carbon atom has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₈is-H; and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₈is-CH₃(ii) a And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R ₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₈is-H; and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r ₈is-CF₃(ii) a And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₈is-H; and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the radicals are attached having the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₈is-OCH₂CH₃(ii) a And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R ₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CH₃And R₉is-H. In another embodimentIn the embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodimentIn, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R ₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R ₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The radicals being linkedThe carbon atom has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₄is-H; r₈Is a-tert-butyl group; and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R ₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₄is-H; r₈is-H; and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; m is 1; r₁is-CH₃-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈is-H; and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyridyl group; n is 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈is-H; and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyrimidinyl group; p is 0; m is 1; r₁is-CH₃-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈is-H; and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyrimidinyl group; p is 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈is-H; and R₉is-Br. In another embodiment, R₃Group attachmentHas the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyridyl group; n is 0; m is 1; r₁is-CH₃-Cl, -Br. or-I; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₄is-H; r₈is-H; and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodimentIn, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyridyl group; n is 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₄is-H; r₈is-H; and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyrimidinyl group; p is 0; m is 1; r₁is-CH₃-Cl, -Br or-I; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₄is-H; r₈is-H; and R₉Is-halo. In another embodiment, R₃The carbon atom to which the radicals are attached having the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyrimidinyl group; p is 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzothiazolyl group; r₄is-H; r₈is-H; and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the radicals are attached having the S structureAnd (4) molding.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) The adjacent carbon atom of the nitrogen of- (when x is 1) or benzothiazolyl (when x is 0) is connected. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) - (when x is 1) or benzothiazolyl (when x is 0) with adjacent carbon atoms to the nitrogen, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) The adjacent carbon atom of the nitrogen of- (when x is 1) or benzothiazolyl (when x is 0) is connected. In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) - (when x is 1) or benzothiazolyl (when x is 0) with adjacent carbon atoms to the nitrogen, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is ₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) The adjacent carbon atom of the nitrogen of- (when x is 1) or benzothiazolyl (when x is 0) is connected. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) - (when x is 1) or benzothiazolyl (when x is 0) with adjacent carbon atoms to the nitrogen, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) The adjacent carbon atom of the nitrogen of- (when x is 1) or benzothiazolyl (when x is 0) is connected. In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) - (when x is 1) or benzothiazolyl (when x is 0) with adjacent carbon atoms to the nitrogen, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodimentM is 1, and R₃Is- (C)₁-C₄) Alkyl, and is attached to the carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidinyl group is attached. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidinyl group is attached, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidinyl group is attached. In another embodiment, m is 1, and R is ₃is-CH₃And is attached to the carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidyl group is attached, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl, and is attached to the carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidinyl group is attached. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidinyl group is attached, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidinyl group is attached. In another embodiment, m is 1, and R is₃is-CH₃And is attached to the carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidyl group is attached, and R₃The carbon atom to which the group is attached has the S configuration.

4.2 Compounds of formula (Ib)

The invention also includes compounds of formula (Ib):

and its medicineA pharmaceutically acceptable salt wherein Ar₁、R₃、R₈、R₉A, x and m are as defined above for the benzoxazole piperazine compound of formula (Ib).

In one embodiment, Ar₁Is a pyrazinyl group.

In another embodiment, Ar₁Is pyridazinyl.

In another embodiment, Ar₁Is thiazanyl.

In another embodiment, x is 1 and A is-C (O) -N (R)₄)-。

In another embodiment, x is 1 and A is-C (S) -N (R)₄)-。

In another embodiment, x is 0.

In another embodiment, p is 0.

In another embodiment, p is 1.

In another embodiment, m is 0.

In another embodiment, m is 1.

In another embodiment, R₄is-H.

In another embodiment, R₄Is- (C)₁-C₆) An alkyl group.

In another embodiment, Ar₁Is pyrazinyl, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, Ar₁Is pyrazinyl, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, Ar₁Is a pyridazinyl group, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, Ar₁Is a pyridazinyl group, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, Ar₁Is thiazanyl, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, Ar₁Is thiazanyl, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, R₁is-H.

In another embodiment, R₁is-Cl.

In another embodiment, R₁is-Br.

In another embodiment, R₁is-I.

In another embodiment, R₁is-F.

In another embodiment, R ₁Is- (C)₁-C₆) An alkyl group.

In another embodiment, R₁is-CH₃。

In another embodiment, R₁is-NO₂。

In another embodiment, R₁is-CN.

In another embodiment, R₁is-OH.

In another embodiment, R₁is-OCH₃。

In another embodiment, R₁is-NH₂。

In another embodiment, R₁is-C (halo)₃。

In another embodiment, R₁is-CH (halo)₂。

In another embodiment, R₁is-CH₂(halo).

In another embodiment, p is 1 and R₂Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, p is 1 and R₂Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅And (4) substituting the group.

In another embodiment, p is 1, and R is₂Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆And (4) substituting the group.

In another embodiment, m is 1, and R is ₃Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, m is 1, and R is₃Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Radical substitution。

In another embodiment, m is 1, and R is₃Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆And (4) substituting the group.

In another embodiment, R₈And R₉Each independently of the others being-H, halo, - (C)₁-C₆) Alkyl, -O (C)₁-C₆) Alkyl, -C (halo)₃-CH (halo)₂or-CH₂(halo).

In another embodiment, at least one R is₈Or R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R) ₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁Is-halo, x is 1,a is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R) ₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁Is-halo x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁Is-halo x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R) ₄)-，R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R ₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodimentP and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R ₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R ₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-CH₃。

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In anotherIn embodiments, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In anotherIn embodiments, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R ₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the radicals are attached having the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R ₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R ₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

At another placeIn one embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH ₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H.In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1,R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R) ₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R) ₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p and m are 0, R₁Is-halo x is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo x is 0, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R ₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R ₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁Is-haloX is 0, R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R ₁is-CH₃X is 0, R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R ₉is-F.

In a further embodiment of the process of the present invention,p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R ₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-CH₃And R₉is-CH₃。

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, and R₈And R₉In another embodiment, R is-H₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-haloX is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R ₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₉The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H, and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃Radical is linked toThe carbon atoms attached have the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH ₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In addition toIn one embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-CH₃. In another embodiment，R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Carbon atoms to which the radicals are attachedHas an S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R ₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R ₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In one embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R ₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Radical (I)The attached carbon atom has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1,R₁is-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R ₄is-H, R₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R ₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R ₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R ₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R ₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R ₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁Is-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached having SConfiguration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-CL. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁Is-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is thiazanyl, p is 0M is 1, R₁Is-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen bound to the benzothiazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R) ₄) The adjacent carbon atom of the nitrogen of- (when x is 1) or benzothiazolyl (when x is 0) is connected. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) - (when x is 1) or benzothiazolyl (when x is 0) with adjacent carbon atoms to the nitrogen, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) - (when x is 1) or benzothiazolyl (whenx is 0) to the adjacent carbon atom. In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) - (when x is 1) or benzothiazolyl (when x is 0) with adjacent carbon atoms to the nitrogen, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) The adjacent carbon atom of the nitrogen of- (when x is 1) or benzothiazolyl (when x is 0) is connected. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) - (when x is 1) or benzothiazolyl (when x is 0) with adjacent carbon atoms to the nitrogen, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R) ₄) The adjacent carbon atom of the nitrogen of- (when x is 1) or benzothiazolyl (when x is 0) is connected. In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) - (when x is 1) or benzothiazolyl (when x is 0) with adjacent carbon atoms to the nitrogen, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyrazinyl, pyridazinyl or thiazanyl group is attached. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyrazinyl, pyridazinyl or thiazanyl radical is attached, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the pyrazinyl, pyridazinyl or thiazanyl group. In another embodiment, m is 1, and R is₃is-CH₃And the carbon adjacent to the nitrogen linking the pyrazinyl, pyridazinyl or thiazanyl radicalIs atomically linked, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyrazinyl, pyridazinyl or thiazanyl group is attached. In another embodiment, m is 1, and R is ₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyrazinyl, pyridazinyl or thiazanyl radical is attached, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the pyrazinyl, pyridazinyl or thiazanyl group. In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the pyrazinyl, pyridazinyl or thiazanyl group, and R₃The carbon atom to which the group is attached has the S configuration.

The invention also includes compounds of formula (IIa):

4.3 Compounds of the formula (IIa)

And pharmaceutically acceptable salts thereof, wherein Ar₁、R₃、R₈、R₉、R₁₀And m is as defined above for the benzoxazole piperazine compound of formula (IIa).

In one embodiment, Ar₁Is a pyridyl group.

In another embodiment, Ar₁Is a pyrimidinyl group.

In another embodiment, Ar₁Is a pyrazinyl group.

In another embodiment, n or p is 0.

In another embodiment, n or p is 1.

In another embodiment, m is 0.

In another embodiment, m is 1.

In another embodiment, R₁₀is-H.

In another embodiment, R₁₀Is- (C)₁-C₄) An alkyl group.

In another embodiment, R ₁₀is-CH₃。

In another embodiment, R₁is-Cl.

In another embodiment, R₁is-Br.

In another embodiment, R₁is-I.

In another embodiment, R₁Is- (C)₁-C₆) An alkyl group.

In another embodiment, R₁is-CH₃。

In another embodiment, R₁is-NO₂。

In another embodiment, R₁is-CN.

In another embodiment, R₁is-OH.

In another embodiment, R₁is-OCH₃。

In another embodiment, R₁is-NH₂。

In another embodiment, R₁is-C (halo)₃。

In another embodiment, R₁is-CH (halo)₂。

In another embodiment, R₁is-CH₂(halo).

In another embodiment, n and p are 1 and R₂Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, n and p are 1 and R₂Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅And (4) substituting the group.

In another embodiment, n and p are 1 and R ₂Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

in another embodiment, m is 1 and R₃Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, m is 1 and R₃Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, whereinEach of which is unsubstituted or is substituted by one or more R₅And (4) substituting the group.

In another embodiment, m is 1 and R₃Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆And (4) substituting the group.

In another embodiment, R₈And R₉Each independently of the others being-H, halo, - (C)₁-C₆) Alkyl, -O (C)₁-C₆) Alkyl, -C (halo)₃-CH (halo)₂or-CH₂(halo).

In another embodiment, at least one R is₈Or R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r ₁is-Cl; r₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈Is-halogeno H and R₉is-H. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-C1; r₄is-H; r₈Is-halo and R₉is-H. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈is-H and R₉is-CH₃. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-C1; r₄is-H; r₈is-H and R₉is-CH₃. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈is-CH₃And R₉is-H. In another embodiment, R ₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl; r₄is-H; r₈is-CH₃And R₉is-H. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈is-H; and R₉is-CF₃. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl; r₄is-H; r₈is-H and R₉is-CF₃. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈is-CF₃And R₉is-H. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl; r₄is-H; r ₈is-CF₃And R₉is-H. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl; r₄is-H; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl; r₄is-H; r₈is-OCH₂CH₃And R₉is-H. In a further embodiment of the process of the present invention,R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r ₁is-Cl, -Br or-I; r₄is-H; r₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl; r₄is-H; r₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈is-CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; r₄is-H; r₈is-CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈is-H and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-Cl; r₄is-H; r₈is-H and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈is-CF₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; r₄is-H; r₈is-CF₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl; r₄is-H; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r ₁is-Cl; r₄is-H; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CH₃，R₄is-H, and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃；R₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-CH₃；R₄is-H; r₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r₁is-CH₃；R₄is-H; r₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-CH₃；R₄is-H; r₈is-CH₃And R₉is-H.

In another embodiment, n isP and m are 0; r₁is-CH₃；R₄is-H; r₈is-H and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-CH₃；R₄is-H; r₈is-CF₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃；R₄is-H; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-CH₃；R₄is-H; r ₈is-OCH₂CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CF₃；R₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CF₃；R₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-CF₃；R₄is-H; r₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r₁is-CF₃；R₄is-H; r₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-CF₃；R₄is-H; r₈is-CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CF₃；R₄is-H; r₈is-H and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-CF₃；R₄is-H; r₈is-CF₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CF₃；R₄is-H; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-CF₃；R₄is-H; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈Is-tert-butyl and R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; r₄is-H; r₈Is-tert-butyl and R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; r₄is-H; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0; r₁is-Cl; r₄is-H; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0; r₁is-CH₃；R₄is-H; r₈Is-tert-butyl and R₉is-H.

In addition toIn one embodiment, n, p and m are 0; r₁is-CH₃；R₄is-H; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0; r₁is-CH₂；R₄is-H; r₈is-CH₃And R₉is-CH₃。

In another embodiment, n is 0, Ar₁Is-2- (3-chloropyridyl) -, m is 1, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₃The carbon atom to which the radicals are attached having the R configuration, R₁₀is-H, R₈Is methyl and R₉Is isopropyl.

In another embodiment, n is 0, Ar₁Is-2- (3-chloropyridyl) -, m is 1, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R ₃The carbon atom to which the radicals are attached having the R configuration, R₁₀is-H, R₈Is isopropyl and R₉Is methyl.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r ₁is-Cl; r₄is-H; r₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzimidazolyl group；R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r ₁is-Cl, -Br or-I; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r ₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Radical-bound carbon atomsThe subunit has an S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0,m is 1, R ₁is-CH₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Group attachmentHas the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃，R₄is-H, R₃is-CH ₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R ₁is-CF₃，R₄is-H, R₃is-CH₃And is connected withAdjacent carbon atoms to benzimidazolyl nitrogen, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃，R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₄is-H; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈Is-tert-butyl and R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₄is-H; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-Cl, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃，R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃，R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃，R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-CH₃And R₉is-CH₃In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyridyl group; n is 0; m is 1; r₁is-CH₃-Cl, -Br or-I; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl n is 0, m is 1, R₁is-CH₃，R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyridyl group; n is 0; m is 1; r₁is-Cl, -Br or-I; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₄is-H; r₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-Cl, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-CH₃，R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R ₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyrimidinyl group; p is 0; m is 1; r₁is-CH₃-Cl, -Br or-I; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-CH₃，R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyrimidinyl group; p is 0; m is 1; r₁is-Cl, -Br or-I; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₄is-H; r₈is-H and R₉is-Br. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-Cl, R₃is-CH₃And with the nitrogen phase bound to the benzimidazolyl groupTo adjacent carbon atoms, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-CH₃，R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyrazinyl group; p is 0; m is 1; r₁is-CH₃-Cl, -Br or-I; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃，R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyrazinyl group; p is 0; m is 1; r₁is-Cl, -Br or-I; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group; r₄is-H; r₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-Cl, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃，R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) An alkyl group and is attached to the carbon atom adjacent to the nitrogen to which the benzimidazolyl group is attached. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group. In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) An alkyl group and is attached to the carbon atom adjacent to the nitrogen to which the benzimidazolyl group is attached. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, and R ₃The carbon atom to which the group is attached is in the S configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group. In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) -or benzimidazolyl nitrogen adjacent to carbon atoms, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyridyl, pyrimidinyl or pyrazinyl group is attached. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and to the carbon atom adjacent to the nitrogen linking the pyridyl, pyrimidinyl or pyrazinyl group, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen to which the pyridyl, pyrimidinyl or pyrazinyl group is attached. In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the pyridyl, pyrimidinyl or pyrazinyl group, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyridyl, pyrimidinyl or pyrazinyl group is attached. In another embodiment, m is 1, and R is ₃Is- (C)₁-C₄) Alkyl and to the carbon atom adjacent to the nitrogen linking the pyridyl, pyrimidinyl or pyrazinyl group, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen to which the pyridyl, pyrimidinyl or pyrazinyl group is attached. In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the pyridyl, pyrimidinyl or pyrazinyl group, and R₃The carbon atom to which the group is attached has the S configuration.

4.4 Compounds of formula (IIb)

The invention also includes compounds of formula (IIb):

and pharmaceutically acceptable salts thereof, wherein Ar₁、R₃、R₈、R₉A, x and m are as defined above for the benzoxazole piperazine compounds of formula (IIb).

In one embodiment, Ar₁Is pyridazinyl.

In another embodiment, Ar₁Is thiazanyl.

In another embodiment, x is 1 and A is-C (O) -N (R)₄)-。

In another embodiment, x is 1 and A is-C (S) -N (R)₄)-。

In another embodiment, x is 0.

In another embodiment, x is 1.

In another embodiment p is 0.

In another embodiment, p is 1.

In another embodiment m is 0.

In another embodiment, m is 1.

In another embodiment, R₄is-H.

In another embodiment, R₄Is- (C)₁-C₆) An alkyl group.

In another embodiment, R₁₀is-H.

In another embodiment, R₁₀Is- (C)₁-C₄) An alkyl group.

In another embodiment, R₁₀is-CH₃。

In another embodiment, Ar₁Is pyrazinyl, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, Ar₁Is pyrazinyl, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, Ar₁Is thiazanyl, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, Ar₁Is thiazanyl, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, R₁is-H.

In another embodiment, R₁is-Cl.

In another embodiment, R₁is-Br.

In another embodiment, R₁is-I.

In another embodiment, R₁is-F.

In another embodiment, R₁Is- (C)₁-C₆) An alkyl group.

In another embodiment, R₁is-CH₃。

In another embodiment, R₁is-NO₂。

In another embodiment, R₁is-CN.

In another embodiment, R₁is-OH.

In another embodiment, R₁is-OCH₃。

In another embodiment, R₁is-NH₂。

In another embodiment, R ₁is-C (halo)₃。

In another embodiment, R₁is-CH (halo)₂。

In another embodiment, R₁is-CH₂(halo).

In another embodiment, p is 1 and R₂Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, p is 1 and R₂Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅And (4) substituting the group.

In another embodiment, p is 1 and R₂Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstitutedOr from one or more R₆Substituted by groups;

in another embodiment, m is 1 and R₃Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, m is 1 and R₃Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R ₅And (4) substituting the group.

In another embodiment, m is 1 and R₃Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆And (4) substituting the group.

In another embodiment, R₈And R₉Each independently of the others being-H, halo, - (C)₁-C₆) Alkyl, -O (C)₁-C₆) Alkyl, -C (halo)₃-CH (halo)₂or-CH₂(halo).

In another embodiment, at least one R is₈Or R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R ₉is-F.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R ₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R ₉is-F.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF ₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-OCH ₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H, and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-CH₃。

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R ₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R ₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached having S configuration。

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R ₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉For the purpose ofH. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁is-CH₃X is 1, A is-C (O) -N (R₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH ₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1,R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) Carbon atoms adjacent to the nitrogen of the radicalIs connected to R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And is connected with-C(O)-N(R₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R) ₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R ₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-、R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-CH₃And R₉is-CH ₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R ₁is-Cl, x is 0, R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R ₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R ₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is H，R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-OCH₂CH₃And H₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R ₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-CH₃And R ₉is-CH₃。

In another embodiment, p is 0 and m is1，R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₁is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈Is-halo and R ₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃Carbon to which radicals are attachedThe atoms have the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R ₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodimentIn embodiments, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to which benzimidazolyl groups are attachedAdjacent carbon atoms of nitrogen, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, and R ₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And is bonded withNitrogen adjacent carbon atoms of imidazolyl are linked, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And is connected with Adjacent carbon atoms to benzimidazolyl nitrogen, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, and R₈And R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉Is-halo. In another embodimentIn, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R ₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈Is a tert-butyl groupAnd R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R) ₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the radicals are attached having the S structureAnd (4) molding.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R) ₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is1, R₁is-CH₃X is1, A is-C (O) -N (R)₄)-，R₄is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is1, R₁is-CH₃Or-halo, x is1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃Carbon to which radicals are attachedThe atoms have the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is1, R₁is-CH₃Xis1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R) ₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R) ₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈For the purpose ofH and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁Is-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R ₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃Radical (I)The attached carbon atom has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁Is-halo, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In a further embodiment of the process of the present invention,R₃the carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzimidazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) The adjacent carbon atoms of the nitrogen of (when x is 1) or benzimidazolyl (when x is 0) are linked. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) - (when x is 1) or benzimidazolyl (when x is 0) with adjacent carbon atoms to the nitrogen, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) The adjacent carbon atoms of the nitrogen of (when x is 1) or benzimidazolyl (when x is 0) are linked. In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) - (when x is 1) or benzimidazolyl (when x is 0) with adjacent carbon atoms to the nitrogen, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) The adjacent carbon atoms of the nitrogen of (when x is 1) or benzimidazolyl (when x is 0) are linked. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) - (when x is 1) or benzimidazolyl (when x is 0) with adjacent carbon atoms to the nitrogen, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) The adjacent carbon atoms of the nitrogen of (when x is 1) or benzimidazolyl (when x is 0) are linked. In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) - (when x is 1) or benzimidazolyl (when x is 0) with adjacent carbon atoms to the nitrogen, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyridazinyl or thiazanyl group is attached. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyridazinyl or thiazanyl radical is attached, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃is-CH ₃And to the carbon atom adjacent to the nitrogen to which the pyridazinyl or thiazanyl group is attached. In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen atom to which the pyridazinyl or thiazanyl radical is attached, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyridazinyl or thiazanyl group is attached. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyridazinyl or thiazanyl radical is attached, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen to which the pyridazinyl or thiazanyl group is attached. In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen atom to which the pyridazinyl or thiazanyl radical is attached, and R₃The carbon atom to which the group is attached has the S configuration.

4.5 Compounds of formula (IIIa)

The invention comprises compounds of formula (IIIa)

And pharmaceutically acceptable salts thereof, wherein Ar₁，R₃，R₈，R₉A, x and m are as described above for

The definition of the benzoxazole piperazine compound of formula (IIIa).

In one embodiment, Ar₁Is a pyridyl group.

In another embodiment, Ar ₁Is a pyrimidinyl group.

In another embodiment, x is 1 and A is-C (O) -N (R)₄)-。

In another embodiment, x is 1 and A is-C (S) -N (R)₄)-。

In another embodiment, x is 0.

In another embodiment x is 1.

In another embodiment n or p is 0.

In another embodiment n or p is 1.

In another embodiment m is 0.

In another embodiment m is 1.

In another embodiment, Ar₁Is pyridyl, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, Ar₁Is pyridyl, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, Ar₁Is pyrimidinyl, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, Ar₁Is pyrimidinyl, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, R₁is-Cl.

In another embodiment, R₁is-Br.

In another embodiment, R₁is-I.

In another embodiment, R₁Is- (C)₁-C₆) An alkyl group.

In another embodiment, R₁is-CH₃。

In another embodiment, R₁is-NO₂。

In another embodiment, R₁is-CN.

In another embodiment, R₁is-OH.

In another embodiment, R₁is-OCH₃。

In another embodiment, R ₁is-NH₂。

In another embodiment, R₁is-C (halo)₃。

In another embodiment, R₁is-CH (halo)₂。

In another embodiment, R₁is-CH₂(halo).

In another embodiment, n and p are 1, and R₂Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, n and p are 1, and R₂Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅And (4) substituting the group.

In another embodiment, n and p are 1, and R₂Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

in another embodiment, m is 1, and R is₃Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, m is 1, and R is₃Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C) ₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅And (4) substituting the group.

In another embodiment, m is 1, and R is₃Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆And (4) substituting the group.

In another embodiment, R₄is-H.

In another embodiment, R₄Is- (C)₁-C₆) An alkyl group.

In another embodiment, R₈And R₉Each independently of the others being-H, halo, - (C)₁-C₆) Alkyl, -O (C)₁-C₆) Alkyl, -C (halo)₃-CH (halo)₂or-CH₂(halo).

In another embodiment, at least one R is₈Or R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) N (R)₄)-；R₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R ₉is-Br. At another placeIn one embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0; r ₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-CH₃And R₉is-H.

In another embodiment, n, p and m are0；R₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-CF₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-CF₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r ₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, n, p and m are 0, R₁is-CH₃X is 1, A is-C (O) - N(R₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-OCH₂C₃H and R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R ₈is-CH₃And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, n, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈Is-tert-butyl and R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈Is-tert-butyl and R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0; r₁is-CH₃X is 1, A is-C (O) -N (R) ₄)-，R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-CH₃。

In another embodiment, n is 0, Ar₁Is-2- (3-nitropyridyl) -, m is 0, x is 0, and R₈And R₉is-H.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1, R₁is-Cl; x is 1, A is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r ₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

At another placeIn one embodiment, n and p are 0; m is 1; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-H and R₉is-CH₃. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-H; and R₉is-CH₃In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-CH₃And R₉is-H. In another embodiment, R₃Group attachmentHas the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is l; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-CF₃And R₉is-H. In another embodiment，R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r ₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₄is-H; r₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R) ₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₈is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In anotherIn embodiments, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉In another embodiment, R is₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R) ₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R ₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈Is-tert-butyl and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached hasAnd R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r₁is-Cl and x is 0; r₄is-H; r₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R ₈is-Br. In another embodiment, R₈is-F.

In anotherIn embodiments, n, p, and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-H and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-H and R₉is-CF₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-CF₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-CF₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r ₄is-H; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃X is 0; r₄is-H, and R₈And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-CH₃X is 0; r₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0; r₁is-CH₃X is 0; r₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0; r₁is-CH₃X is 0; r₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CH ₃X is 0, R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, n, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CF₃X is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, n, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, n, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, n, p and m are 0, R₁is-CF ₃X is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, n, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, n, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, n, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈Is-tert-butyl and R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈Is-tert-butyl and R₉is-H.

In another embodiment, n, p and m are 0; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0; r₁is-Cl; x is 0; r₄is-H; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈Is tert-butyl andR₉is-H.

In another embodiment, n, p and m are 0, R₁is-CH ₃X is 0, R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, n, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-CH₃And R₉is-CH₃。

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1, R₁is-Cl; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen atom to which the benzoxazolyl group is attached, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R ₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1, R₁is-Cl; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And is connected withA nitrogen adjacent to the benzoxazolyl group is attached to a carbon atom; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1, R₁is-Cl; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 0; r₄is-H; r₄is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r ₁is-Cl; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r ₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 0; r₄is-H; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen atom to which the benzoxazolyl group is attached, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R ₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment，R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen atom to which the benzoxazolyl group is attached, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R ₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Carbon to which radicals are attachedThe atoms have the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r ₁is-Cl, -Br or-I; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₄is-H; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₄is-H; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0; m is 1; r₁is-Cl; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r ₄is-H; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, n and p are 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-CH₃And R₉is-CH₃. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyridyl group; n is 0; m is 1; r₁is-CH₃-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -NC (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is a pyridyl group; n is 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R ₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -NC (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is a pyrimidinyl group; p is 0; m is 1; r₁is-CH₃-Cl, -Br, -I; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is a pyrimidinyl group; p is 0; m is 1; r₁is-Cl, -Br or-I; x is 1; a is-C (O) -N (R)₄)-；R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom; r₄is-H; r₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is a pyridyl group; n is 0; m is 1; r₁is-CH₃-Cl, -Br or-I; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is a pyridyl group; n is 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₄is-H; r₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is pyridyl, n is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is a pyrimidinyl group; p is 0; m is 1; r₁is-CH₃Cl, -Br or-I; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₄is-H; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is a pyrimidinyl group; p is 0; m is 1; r₁is-Cl, -Br or-I; x is 0; r₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the benzoxazolyl group; r₄is-H; r₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) -or a nitrogen of the benzoxazolyl group is attached adjacent to a carbon atom. In another embodiment, m is 1, and R₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) -or nitrogen of benzoxazolyl is attached to adjacent carbon atoms, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) -or a nitrogen of the benzoxazolyl group is attached adjacent to a carbon atom. In another embodiment, m is 1, and R₃is-CH₃And to the linkage-C (O) -N (R)₄) -or nitrogen of benzoxazolyl is attached to adjacent carbon atoms, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) -or a nitrogen of the benzoxazolyl group is attached adjacent to a carbon atom. In another embodiment, m is 1, and R ₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) -or nitrogen of benzoxazolyl is attached to adjacent carbon atoms, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) -or a nitrogen of the benzoxazolyl group is attached adjacent to a carbon atom. In another embodiment, m is 1, and R₃is-CH₃And to the linkage-C (O) -N (R)₄) -or nitrogen of benzoxazolyl is attached to adjacent carbon atoms, and R₃Group attachmentHas the S configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidinyl group is attached. In another embodiment, m is 1, and R₃Is- (C)₁-C₄) Alkyl and to a carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidinyl group is attached, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidinyl group is attached. In another embodiment, m is 1, and R₃is-CH₃And to a carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidyl group is attached, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is ₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidinyl group is attached. In another embodiment, m is 1, and R₃Is- (C)₁-C₄) Alkyl and to a carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidinyl group is attached, and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidinyl group is attached. In another embodiment, m is 1, and R₃is-CH₃And to a carbon atom adjacent to the nitrogen to which the pyridyl or pyrimidyl group is attached, and R₃The carbon atom to which the group is attached has the S configuration.

4.6 Compounds of formula (IIIb)

The invention also includes compounds of formula (IIIb):

and pharmaceutically acceptable salts thereof, wherein Ar₁、R₃、R₈、R₉A, x and m are as above

The definition of the benzoxazole piperazine compound of the formula (IIIb) is described below.

In one embodiment, Ar₁Is a pyrazinyl group.

In another embodiment, Ar₁Is pyridazinyl.

In another embodiment, Ar₁Is thiazanyl.

In another embodiment, x is 1 and A is-C (O) -N (R)₄)-。

In another embodiment, x is 1 and A is-C (S) -N (R)₄)-。

In another embodiment, x is 0.

In another embodiment, x is 1.

In another embodiment, p is 0.

In another embodiment, p is 1.

In another embodiment, m is 0.

In another embodiment, m is 1.

In another embodiment, Ar₁Is pyrazinyl, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, Ar₁Is pyrazinyl, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, Ar₁Is a pyridazinyl group, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, Ar₁Is a pyridazinyl group, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, Ar₁Is thiazanyl, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, Ar₁Is thiazanyl, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, R₁is-H.

In another embodiment, R₁is-Cl.

In another embodiment, R₁is-Br.

In another embodiment, R₁is-I.

In another embodiment, R₁is-F.

In another embodiment, R₁Is- (C)₁-C₆) An alkyl group.

In another embodiment, R₁is-CH₃。

In another embodiment, R₁is-NO₂。

In another embodiment, R₁is-CN.

In another embodiment, R₁is-OH.

In another embodiment, R₁is-OCH ₃。

In another embodiment, R₁is-NH₂。

In another embodiment, R₁is-C (halo)₃。

In another embodiment, R₁is-CH (halo)₂。

In another embodiment, R₁is-CH₂(halo).

In another embodiment, p is 1 and R₂Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, p is 1 and R₂Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅And (4) substituting the group.

In another embodiment, p is 1 and R₂Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

in another embodiment, m is 1 and R₃Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, m is 1 and R₃Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C) ₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅And (4) substituting the group.

In another embodiment, m is 1 and R₃Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆And (4) substituting the group.

In another embodiment, R₄is-H.

In another embodiment, R₄Is- (C)₁-C₆) An alkyl group.

In another embodiment, R₈And R₉Each independently of the others being-H, halo, - (C)₁-C₆) Alkyl, -O (C)₁-C₆) Alkyl, -C (halo)₃-CH (halo)₂or-CH₂(halo).

In another embodiment, at least one R is₈Or R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R ₉is-F.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R ₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₉is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment In which p and m are 0 and R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p andm is 0, R₁is-CH₃X is 1, A is-C (O) -N (R) ₄)-，R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁For the purpose ofCF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R ₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₈is-CH₃And R₉is-CH₃。

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R) ₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R ₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH ₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R ₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈Is-halo and R₉is-H. In another embodiment, R ₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉For the purpose ofCH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R ₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is attached to an adjacent carbon atom,R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0 and m is1，R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R ₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R ₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the radicals are attached having the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 1, A is-C (O) -N (R)₄)-，R₄is-H, R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R ₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodimentIn, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-Cl and x is 0，R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R ₁Is-halo, x is 0, R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉is-CF₃。

In another embodimentIn the formula, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R ₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0 and Rt is-CH₃X is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

At another placeIn one embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₉Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R ₈is-F.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, and R₈And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉Is-halo. At another placeIn one embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R ₈is-Br. In another embodiment, R₈is-F.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉is-CH₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉is-CF₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-CF₃And R₉is-H.

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-H and R₉is-OCH₂CH₃。

In another embodiment, p and m are 0, R₁is-CF₃X is 0, R₄is-H, R₈is-OCH₂CH₃And R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁Is-halo, x is 0, R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-Cl, x is 0, R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R ₁is-CH₃X is 0, R₄is-H, R₈Is-tert-butyl and R₉is-H.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-H and R₉Is a tert-butyl group.

In another embodiment, p and m are 0, R₁is-CH₃X is 0, R₄is-H, R₈is-CH₃And R₉is-CH₃。

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen atom to which the benzoxazolyl group is attached, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen atom to which the benzoxazolyl group is attached, and R₈And R₉is-H. In another embodiment, R₃Radical is linked toThe carbon atoms attached have the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R ₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In a further embodiment of the process of the present invention,p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-CH ₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R ₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment，R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen atom to which the benzoxazolyl group is attached, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R ₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R ₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In addition toIn one embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to the carbon atom adjacent to the nitrogen atom to which the benzoxazolyl group is attached, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉Is-halo. In another embodiment, R₉is-Cl. In another embodiment, R₉is-Br. In another embodiment, R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈Is-halo and R₉is-H. In another embodiment, R₈is-Cl. In another embodiment, R ₈is-Br. In another embodiment, R₈is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-CF₃And R₉is-H. In another embodiment, R₃Carbon atoms to which the radicals are attachedHas the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CF₃X is 0, R₄is-H, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R ₁Is-halo, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁Is-halo, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R ₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And with nitrogen phase bound to benzoxazolyl groupTo adjacent carbon atoms, R₄is-H, R₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodimentIn the scheme, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁Is-halo, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-Cl, x is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃X is 1, A is-C (O) -N (R)₄)-，R₃is-CH₃And to the linkage-C (O) -N (R)₄) -the nitrogen of the group is adjacent to a carbon atom, R₄is-H, R₈is-H and R₉is-F. In another implementationIn the scheme, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁Is-halo, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. At another placeIn one embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrazinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridazinyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁Is-halo, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached hasAnd (4) S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridazinyl, p is 0, m is 1, R₁is-CH ₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃Or-halo, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-Cl. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁Is-halo, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R ₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-Cl, x is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-Br. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is thiazanyl, p is 0, m is 1, R₁is-CH₃X is 0, R₃is-CH₃And to a carbon atom adjacent to the nitrogen linking the benzoxazolyl group, R₄is-H, R₈is-H and R₉is-F. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) The adjacent carbon atoms of the nitrogen (when x is 1) or the benzoxazolyl (when x is 0) are linked. In another embodiment, m is 1, and R is ₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) - (when x is 1) or benzoxazolyl (when x is 0) with the adjacent carbon atoms of the nitrogen and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) The adjacent carbon atoms of the nitrogen (when x is 1) or the benzoxazolyl (when x is 0) are linked. In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) - (when x is 1) or benzoxazolyl (when x is 0) with the adjacent carbon atoms of the nitrogen and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) The adjacent carbon atoms of the nitrogen (when x is 1) or the benzoxazolyl (when x is 0) are linked. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and with a linkage-C (O) -N (R)₄) - (when x is 1) or benzoxazolyl (when x is 0) with the adjacent carbon atoms of the nitrogen and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the linkage-C (O) -N (R)₄) The adjacent carbon atoms of the nitrogen (when x is 1) or the benzoxazolyl (when x is 0) are linked. In another embodiment, m is 1, and R is ₃is-CH₃And to the linkage-C (O) -N (R)₄) - (when x is 1) or benzoxazolyl (when x is 0) with the adjacent carbon atoms of the nitrogen and R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyrazinyl, pyridazinyl or thiazanyl group is attached. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyrazinyl, pyridazinyl or thiazanyl radical is attached, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the pyrazinyl, pyridazinyl or thiazanyl group. In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the pyrazinyl, pyridazinyl or thiazanyl group, and R₃The carbon atom to which the group is attached has the R configuration.

In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyrazinyl, pyridazinyl or thiazanyl group is attached. In another embodiment, m is 1, and R is₃Is- (C)₁-C₄) Alkyl and is attached to the carbon atom adjacent to the nitrogen to which the pyrazinyl, pyridazinyl or thiazanyl radical is attached, and R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the pyrazinyl, pyridazinyl or thiazanyl group. In another embodiment, m is 1, and R is₃is-CH₃And to the carbon atom adjacent to the nitrogen linking the pyrazinyl, pyridazinyl or thiazanyl group, and R₃The carbon atom to which the group is attached has the S configuration.

4.7 Compounds of formula (IVa)

The invention also includes compounds of formula (IVa):

and pharmaceutically acceptable salts thereof, wherein Ar₁、Ar₂And R₃As defined above for the benzoxazole piperazine compound of formula (IVa).

In one embodiment, Ar₁Is a pyridyl group.

In another embodiment, Ar₁Is a pyrimidinyl group.

In another embodiment, Ar₂Is a benzothiazolyl group.

In another implementationIn scheme (II), Ar₂Is benzoxazolyl.

In another embodiment, Ar₂Is a benzimidazolyl group.

In another embodiment, n or p is 0.

In another embodiment, n or p is 1.

In another embodiment, R₁is-Cl.

In another embodiment, R₁is-Br.

In another embodiment, R₁is-I.

In another embodiment, R₁is-F.

In another embodiment, R₁Is- (C)₁-C₆) An alkyl group.

In another embodiment, R₁is-CH₃。

In another embodiment, R₁is-NO₂。

In another embodiment, R₁is-CN.

In another embodiment, R₁is-OH.

In another embodiment, R₁is-OCH₃。

In another embodiment, R₁is-NH₂。

In another embodiment, R₁is-C (halo)₃。

In another embodiment, R₁is-CH (halo)₂。

In another embodiment, R₁is-CH₂(halo).

In another embodiment, n and p are 1 and R₂Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, n and p are 1 and R₂Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅And (4) substituting the group.

In another embodiment, n and p are 1 and R₂Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

In another embodiment, R₃is-H.

In another embodiment, R₃is-CH₃。

In another embodiment, R₈And R₉Each independently of the others being-H, halo, - (C)₁-C₆) Alkyl, -O (C)₁-C₆) Alkyl, -C (halo)₃-CH (halo)₂or-CH₂(halo).

In another embodiment, at least one R is₈And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; and R₈And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; and R₈And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r ₈is-H and R₉Is-fluoro.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r ₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r ₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r ₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, Ar₁Is pyridyl, n is0；R₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In anotherIn embodiments, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, the AR₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodimentIn the embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r ₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r ₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In a further embodiment of the process of the present invention,Ar₁is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-Ch₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In a further embodiment of the process of the present invention,R₃the carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; and R₈And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; and R₈And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar) ₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H.

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃。

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H.

In another embodiment, Ar₁Is a pyrimidinyl groupP is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atoms of which are bound by radicalsHas an S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and A₉is-H.In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r ₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached having S configuration 。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; and R ₈And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; and R₈And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r ₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r ₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r ₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0；R₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, Ar ₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R ₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃Radical-bound carbon atomsAnd the subunit has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH ₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In anotherIn embodiments, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; and R₈And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; and R₈And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo.

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R ₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R ₉is-CH₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H; and R₉is-OCH₂CH₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H;R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r ₈is-H and R₉is-OCH₂CH₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃Group attachmentHas the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodimentIn the scheme, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH ₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In a further embodiment of the process of the present invention,Ar₁is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; and R₈And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; and R₈And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-halo.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-bromo.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r ₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r1 is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo andR₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H.

In another embodiment, Ar ₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; a. ther₂Is benzoxazolyl; r₈is-CF₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃(ii) a And R₉is-H.

In another embodiment, Ar ₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is0；R₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r ₈Is-chloro and R₉is-H. In a further embodiment of the process of the present invention,R₃the carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r ₃is-CH₃；R₁is-F, -Cl, -Br or-I; (ii) a Ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; (ii) a Ar (Ar)₂Is benzoxazolyl; and R₈And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; and R₈And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-halo.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-FAr₂Is benzoxazolyl; r₈is-H and R₉Is-bromo.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar) ₂Is benzoxazolyl; r₈Is-halo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzeneAn oxazolyl group; r₈Is-bromo and R₉is-H.

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; (ii) a Ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃。

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃。

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-H; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodimentIn, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH ₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the radicals are attached having the R structureAnd (4) molding. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached having SConfiguration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group.In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₃is-CH₃；R₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

4.8 Compounds of formula (IVb)

The invention also includes compounds of formula (IVb)

And pharmaceutically acceptable salts thereof, wherein Ar₁、Ar₂，、A、R₃And x is as defined above for the benzoxazole piperazine compound of formula (IVb).

In one embodiment, Ar₁Is a pyridyl group.

In another embodiment, Ar₁Is a pyrimidinyl group.

In another embodiment, n or p is 0.

In another embodiment, n or p is 1.

In another embodiment, x is 0.

In another embodiment, x is 1.

In another embodiment, R₁is-F.

In another embodiment, R₁is-Cl。

In another embodiment, R₁is-Br.

In another embodiment, R₁is-I.

In another embodiment, R₁Is- (C)₁-C₆) An alkyl group.

In another embodiment, R₁is-CH₃。

In another embodiment, R₁is-NO₂。

In another embodiment, R₁is-CN.

In another embodiment, R₁is-OH.

In another embodiment, R₁is-OCH₃。

In another embodiment, R₁is-NH₂。

In another embodiment, R₁is-C (halo)₃。

In another embodiment, R₁is-CH (halo)₂。

In another embodiment, R₁is-CH₂(halo).

In another embodiment, n and p are 1 and R₂Is-halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂。

In another embodiment, n and p are 1 and R₂Is- (C)₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C) ₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅And (4) substituting the group.

In another embodiment, n and p are 1 and R₂Is-phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

in another embodiment, x is 1 and A is-C (O) N (R)₄)-。

In another embodiment, x is 1, A is-C (O) N (R)₄) -and R₄is-H.

In another embodiment, x is 1, A is-C (O) N (R)₄) -and R₄is-CH₃。

In another embodiment, x is 1 and A is-C (S) N (R)₄)-。

In another embodiment, x is 1, A is-C (S) N (R)₄) -and R₄is-H.

In another embodiment, x is 1, A is-C (S) N (R)₄) -and R₄is-CH₃。

In another embodiment, Ar₂Is a benzothiazolyl group.

In another embodiment, Ar₂Is a benzimidazolyl group.

In another embodiment, Ar₂Is benzoxazolyl.

In another embodiment, R₈And R₉Each independently is-H, halo, - (CX-C) ₆) Alkyl, -O (C)₁-C₆) Alkyl, -C (halo)₃-CH (halo)₂or-CH₂(halo).

In another embodiment, at least one R is₈Or R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; r₄is-H; ar (Ar)₂Is a benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; r₄is-H; ar (Ar)₂Is benzothiazolyl, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar) ₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In a further embodiment of the process of the present invention,R₃the carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the radicals are attached having the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyridyl groupN is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r ₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar) ₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group;R₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁For the purpose ofCH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r ₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r ₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyridyl group, and the pyridyl group,n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁For the purpose ofCF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyridyl groupN is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; r₄is-H; ar (Ar)₂Is a benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; r₄is-H; ar (Ar)₂Is benzothiazolyl, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In anotherIn embodiments, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In addition toIn one embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r ₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; and R ₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzothiazoleA group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R ₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-bromo and R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzothiazoleA group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group；R₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; r₄is-H; ar (Ar)₂Is a benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; r₄is-H; ar (Ar)₂Is benzimidazolyl, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I;Ar₂is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. At another placeIn one embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃Carbon atoms to which the radicals are attachedHas the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the radicals are attached having the R structureAnd (4) molding. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar) ₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r ₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodimentIn, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r ₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH ₃；Ar₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃Radical is linked toThe carbon atoms attached have the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH ₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r ₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another implementation In the scheme, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r1 is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃Radical (I)The attached carbon atom has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃Radical is linked toThe carbon atoms attached have the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In thatIn another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In a further embodiment of the process of the present invention,R₃the carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; r₄is-H; ar (Ar)₂Is a benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F.R₄is-H; ar (Ar)₂Is benzimidazolyl, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In thatIn another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H.

In another embodimentIn the scheme, Ar₁Is pyrimidinyl, p is 0; r1 is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0；R₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzeneAn imidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyrimidyl group and a pharmaceutically acceptable salt thereof,p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r ₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is a pyrimidyl group and a pharmaceutically acceptable salt thereof,p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r ₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is0；R₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R ₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-fluoro and R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-tert-butyl and R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; r₄is-H; ar (Ar)₂Is benzoxazolyl; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; r₄is-H; ar (Ar) ₂Is benzoxazolyl, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment In Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the radicals are attached having the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar) ₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Radical-bound carbon atomsThe subunit has an S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r ₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Carbon to which radicals are attachedThe atoms have the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Radical is linked to The carbon atom to which it is attached has S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Group attachmentHas the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another implementationIn the scheme, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r ₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF ₃；Ar₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Group attachmentHas the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF ₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r ₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another implementationIn the scheme, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar) ₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodimentIn the scheme, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl, n is 0; r ₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; r₄is-H; ar (Ar)₂Is benzoxazolyl; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; r₄is-H; ar (Ar)₂Is benzoxazolyl, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the radicals are attached having the R structureAnd (4) molding. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the radicals are attached having the R structureAnd (4) molding. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached hasAnd (4) S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r ₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazoleA group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CF₃In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r ₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r ₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R ₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl;R₈is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-fluoro and R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CF₃；AR₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl,-Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₄is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-tert-butyl and R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; r₄is-H; ar (Ar)₂Is a benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; r₄is-H; ar (Ar) ₂Is benzothiazolyl, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F,-Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; AR₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro andR₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In anotherIn embodiments, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃Radical-bound carbon atomsAnd the subunit has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The radicals being linkedThe carbon atom has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. At another placeIn one embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment，R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. At another placeIn one embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r ₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r ₈is-H and R₉Is-bromo. In anotherIn embodiments, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r ₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In a further embodiment of the process of the present invention,R₃the carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R ₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodimentIn, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R ₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r ₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; r₄is-H; ar (Ar)₂Is a benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; r₄is-H; ar (Ar)₂Is benzothiazolyl, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r ₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H andR₉is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁Is Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodimentIn the scheme, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃Radical is linked toThe carbon atoms attached have the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another implementationIn the scheme, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Radical is linked toThe carbon atom to which it is attached has S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the radicals are attached having the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodimentIn the embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment，R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The radicals being linkedThe carbon atom has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r ₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r ₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF ₃；Ar₂Is a benzothiazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another implementationIn the scheme, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r ₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In addition toIn one embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzothiazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r ₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The radicals being linkedThe carbon atom has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r ₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzothiazolyl group; r₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; r₄is-H; ar (Ar)₂Is a benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl and n is 0; r₁is-F, R₄is-H; ar (Ar)₂Is benzimidazolyl, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another implementationIn the scheme, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo; and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar) ₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r ₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Group attachmentHas the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r ₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH ₃；Ar₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached hasAnd (4) S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH ₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the radicals are attached having the S structureAnd (4) molding.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r ₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The radicals being linkedThe carbon atom has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the radicals are attached having the S structureAnd (4) molding.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; r₄is-H; ar (Ar)₂Is a benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; r₄is-H; ar (Ar)₂Is benzimidazolyl, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In anotherIn embodiments, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In anotherIn embodiments, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r ₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r ₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r1 is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r ₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In a further embodiment of the process of the present invention,Ar₁is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

At another placeIn one embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In addition to In one embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.

In anotherIn embodiments, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r ₁is-CF₃；Ar₂Is a benzimidazolyl group; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r ₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-bromo and R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In anotherIn embodiments, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is a benzimidazolyl group; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is a benzimidazolyl group; r₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; r₄is-H; ar (Ar)₂Is benzoxazolyl; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; r₄is-H; ar (Ar)₂Is benzoxazolyl, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodimentIn the scheme, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the radicals are attached having the R structureAnd (4) molding. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment，R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r ₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃Radical-bound carbon atomsAnd the subunit has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH ₃；Ar₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment，R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r ₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R ₉Is-bromo. In a further embodiment of the process of the present invention,R₃the carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-chloro and R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃Radical (I)The attached carbon atom has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CH ₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H. In anotherIn embodiments, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R ₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyridyl and n is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r ₈is-CH₃And R₉is-CH₃. In addition toIn one embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; r₄is-H; ar (Ar)₂Is benzoxazolyl; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; r₄is-H; ar (Ar)₂Is benzoxazolyl, and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r ₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-bromineAnd (4) generation. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-Cl; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atoms of which are bound by radicalsHas the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Radical (I)The attached carbon atom has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached having SConfiguration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R ₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment ，R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃，Ar₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-fluoro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar ₁Is pyrimidinyl and p is 0; r₁is-CH₃，Ar₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Group attachmentHas the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r ₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In thatIn another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; and R₈And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r ₈is-H and R₉Is-halo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-chloro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-bromo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is-fluoro. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In a further embodiment of the process of the present invention,R₃the carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R ₉Is-iodo. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-halo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-chloro and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-bromo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-fluoro and R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃Radical (I)The attached carbon atom has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈Is-iodo and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-CF₃. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-CF₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-H and R₉is-OCH₂CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CF₃；Ar₂Is benzoxazolyl; r₈is-OCH₂CH₃And R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H. In another embodiment, R ₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈Is-tert-butyl and R₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F, -Cl, -Br or-I; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration.In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-F; ar (Ar)₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈Is-tert-butyl and R ₉is-H. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl and p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-H and R₉Is a tert-butyl group. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-CH₃And R₉is-CH₃. In another embodiment, R₃The carbon atom to which the group is attached has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In another embodiment, Ar₁Is pyrimidinyl, p is 0; r₁is-CH₃；Ar₂Is benzoxazolyl; r₈is-CH₃And R₉is-CH₃. In another embodiment, R₃Radical-bound carbon atomsAnd the subunit has the R configuration. In another embodiment, R₃The carbon atom to which the group is attached has the S configuration.

In the benzoxazole piperazine compound, R₃The group may be on any carbon atom on the piperazine ring. In one embodiment, R ₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or thiazanyl group is attached. In another embodiment, when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached.

In one embodiment, wherein the benzoxazole piperazine compound has R₃Group, R₃The carbon atom to which the group is attached has the (R) configuration. In another embodiment, wherein the benzoxazole piperazine compound has R₃Group, R₃The carbon atom to which the group is attached has the (S) configuration.

In another embodiment, the benzoxazole piperazine compound has R₃A group; r₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or thiazanyl group is attached; and R₃The carbon atom to which the group is attached is in the (R) configuration. In another embodiment, the benzoxazole piperazine compound has R₃A group; r₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or thiazanyl group is attached; r₃The carbon atom to which the group is attached is in the (R) configuration; and R ₃Is unsubstituted or substituted by one or more halo groups- (C)₁-C₄) An alkyl group. In another embodiment, the benzoxazole piperazine compound has R₃A group; r₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or thiazanyl group is attached; r₃The carbon atom to which the group is attached is in the (R) configuration; and R₃is-CH₃. In another embodiment, the benzoxazole piperazine isThe oxazine compound has R₃A group; r₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or thiazanyl group is attached; r₃The carbon atom to which the group is attached is in the (R) configuration; and R₃is-CF₃. In another embodiment, the benzoxazole piperazine compound has R₃A group; r₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or thiazanyl group is attached; r₃The carbon atom to which the group is attached is in the (R) configuration; and R₃is-CH₂CH₃。

In another embodiment, the benzoxazole piperazine compound has R₃A group; when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; and R ₃The carbon atom to which the group is attached is in the (R) configuration. In another embodiment, the benzoxazole piperazine compound has R₃A group; when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; r₃The carbon atom to which the group is attached is in the (R) configuration; and R₃Is unsubstituted or substituted by one or more halo groups- (C)₁-C₄) An alkyl group. In another embodiment, the benzoxazole piperazine compound has R₃A group; when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; r₃The carbon atom to which the group is attached is in the (R) configuration; and R₃is-CH₃. In another embodiment, the benzoxazole piperazine compound has R₃A group; when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or whenWhen x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; r ₃The carbon atom to which the group is attached is in the (R) configuration; and R₃is-CF₃. In another embodiment, the benzoxazole piperazine compound has R₃A group; when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; r₃The carbon atom to which the group is attached is in the (R) configuration; and R₃is-CH₂CH₃。

In another embodiment, the benzoxazole piperazine compound has R₃A group; r₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or thiazanyl group is attached; and R₃The carbon atom to which the group is attached is in the (S) configuration. In another embodiment, the benzoxazole piperazine compound has R₃A group; r₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or thiazanyl group is attached; r₃The carbon atom to which the group is attached is in the (S) configuration; and R₃Is unsubstituted or substituted by one or more halo groups- (C)₁-C₄) An alkyl group. In another embodiment, the benzoxazole piperazine compound has R₃A group; r₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or thiazanyl group is attached; r ₃The carbon atom to which the group is attached is in the (S) configuration; and R₃is-CH₃. In another embodiment, the benzoxazole piperazine compound has R₃A group; r₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or thiazanyl group is attached; r₃The carbon atom to which the group is attached is in the (S) configuration; and R₃is-CF₃. In another embodiment, the benzoxazole piperazine compound has R₃A group; r₃The group and the linking pyridyl group,The nitrogen atoms of the pyrimidinyl, pyrazinyl, pyridazinyl or thiazanyl group are attached adjacent to one another; r₃The carbon atom to which the group is attached is in the (S) configuration; and R₃is-CH₂CH₃。

In another embodiment, the benzoxazole piperazine compound has R₃A group; when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; and R₃The carbon atom to which the group is attached is in the (S) configuration. In another embodiment, the benzoxazole piperazine compound has R₃A group; when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R ₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; r₃The carbon atom to which the group is attached is in the (S) configuration; and R₃Is unsubstituted or substituted by one or more halo groups- (C)₁-C₄) An alkyl group. In another embodiment, the benzoxazole piperazine compound has R₃A group; when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; r₃The carbon atom to which the group is attached is in the (S) configuration; andis-CH₃. In another embodiment, the benzoxazole piperazine compound has R₃A group; when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; r₃The carbon atom to which the group is attached is in the (S) configuration; and R₃is-CF₃. In another embodiment, benzeneThe azole piperazine compound has R₃A group; when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R ₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; r₃The carbon atom to which the group is attached is in the (S) configuration; and R₃is-CH₂CH₃。

In a preferred embodiment, when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; and R₃The group being-CH₃. In another preferred embodiment, when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group being bound to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached, and R₃The radical being-CF₃. In another preferred embodiment, when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; and R₃The group being-CH₂CH₃In another preferred embodiment, when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R ₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; and R₃The carbon atom to which the group is attached is in the (R) configuration. In another preferred embodiment, when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; r₃The carbon atom to which the group is attached is in the (R) configuration; and R₃The group being-CH₃. In another preferred embodiment, when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; r₃The carbon atom to which the group is attached is in the (R) configuration; and R₃The radical being-CF₃In another preferred embodiment, when x is 1, R₃The group is attached to the carbon atom adjacent to the nitrogen atom to which the- (A) -group is attached; or when x is 0, R₃The group is attached to a carbon atom adjacent to the nitrogen atom to which the benzothiazolyl, benzimidazolyl or benzoxazolyl group is attached; r₃The carbon atom to which the group is attached is in the (R) configuration; and R ₃The group being-CH₂CH₃。

Exemplary benzoxazole piperazine compounds are listed in tables I-XXII below:

TABLE I

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				AAA	-2- (3-chloropyridyl)	-Cl	-H
AAB	-2- (3-chloropyridyl)	-Br	-H
				AAC	-2- (3-chloropyridyl)	-F	-H
AAD	-2- (3-chloropyridyl)	-CH	-H
				AAE	-2- (3-chloropyridyl)	-CF	-H
AAF	-2- (3-chloropyridyl)	-OCH	-H
				AAG	-2- (3-chloropyridyl)	-OCHCH	-H
AAH	-2- (3-chloropyridyl)	-OCF	-H
				AAI	-2- (3-chloropyridyl)	-tert-butyl	-H
AAJ	-2- (3-chloropyridyl)	-isopropyl group	-H
				AAK	-2- (3-chloropyridyl)	-CH	-CH
AAL	-2- (3-chloropyridyl) -	H	-H

AAM	-2- (3-chloropyridyl)	-H	-Cl
				AAN	-2- (3-chloropyridyl)	-H	-Br
AAO	-2- (3-chloropyridyl)	-H	-F
				AAP	-2- (3-chloropyridyl)	-H	-CH
AAQ	-2- (3-chloropyridyl)	-H	-CF
				AAR	-2- (3-chloropyridyl)	-H	-OCH
AAS	-2- (3-chloropyridyl)	-H	-OCHCH
				AAT	-2- (3-chloropyridyl)	-H	-OCF
AAU	-2- (3-chloropyridyl)	-H	-tert-butyl
				AAV	-2- (3-chloropyridyl)	-H	-isopropyl group
AAW	-2- (3-methylpyridinyl)	-Cl	-H
				AAX	-2- (3-methylpyridinyl)	-Br	-H
AAY	-2- (3-methylpyridinyl)	-F	-H
				AAZ	-2- (3-methylpyridinyl)	-CH	-H
ABA	-2- (3-methylpyridinyl)	-CF	-H
				ABB	-2- (3-methylpyridinyl)	-OCH	-H
ABC	-2- (3-methylpyridinyl)	-OCHCH	-H
				ABD	-2- (3-methylpyridinyl)	-OCF	-H
ABE	-2- (3-methylpyridinyl)	-tert-butyl	-H
				ABF	-2- (3-methylpyridinyl)	-isopropyl group	-H
ABG	-2- (3-methylpyridinyl)	-CH	-CH
				ABH	-2- (3-methylpyridinyl)	-H	-H
ABI	-2- (3-methylpyridinyl)	-H	-Cl
				ABJ	-2- (3-methylpyridinyl)	-H	-Br
ABK	-2- (3-methylpyridinyl)	-H	-F
				ABL	-2- (3-methylpyridinyl)	-H	-CH
ABM	-2- (3-methylpyridinyl)	-H	-CF

ABN	-2- (3-methylpyridinyl)	-H	-CCH
				ABO	-2- (3-methylpyridinyl)	-H	-OCHCH
ABP	-2- (3-methylpyridinyl)	-H	-OCF
				ABQ	-2- (3-methylpyridine)Base)	-H	-tert-butyl
ABR	-2- (3-methylpyridinyl)	-H	-isopropyl group
				ABS	-2-(3-CF-pyridyl group)	-Cl	-H
ABT	-2-(3-CF-pyridyl group)	-Br	-H
				ABU	-2-(3-CF-pyridyl group)	-F	-H
ABV	-2-(3-CF-pyridyl group)	-CH	-H
				ABW	-2-(3-CF-pyridyl group)	-CF	-H
ABX	-2-(3-CF-pyridyl group)	-OCH	-H
				ABY	-2-(3-CF-pyridyl group)	-OCHCH	-H
ABZ	-2-(3-CF-pyridyl group)	-OCF	-H
				ACA	-2-(3-CF-pyridyl group)	-tert-butyl	-H
ACB	-2-(3-CF-pyridyl group)	-isopropyl group	-H
				ACC	-2-(3-CF-pyridyl group)	-CH	-CH
ACD	-2-(3-CF-pyridyl group)	-H	-H
				ACE	-2-(3-CF-pyridyl group)	-H	-Cl
ACF	-2-(3-CF-pyridyl group)	-H	-Br
				ACG	-2-(3-CF-pyridyl group)	-H	-F
ACH	-2-(3-CF-pyridyl group)	-H	-CH
				ACI	-2-(3-CF-pyridyl group)	-H	-CF
ACJ	-2-(3-CF-pyridyl group)	-H	-OCH
				ACK	-2-(3-CF-pyridyl group)	-H	-OCHCH
ACL	-2-(3-CF-pyridyl group)	-H	-OCF
				ACM	-2-(3-CF-pyridyl group)	-H	-tert-butyl
CAN	-2-(3-CF-pyridyl group)	-H	-isopropyl group

ACO	-4- (5-chloropyrimidinyl)	-Cl	-H
				ACP	-4- (5-chloropyrimidinyl)	-Br	-H
ACQ	-4- (5-chloropyrimidinyl)	-F	-H
				ACR	-4- (5-chloropyrimidinyl)	-CH	-H
ACS	-4- (5-chloropyrimidinyl)	-CF	-H
				ACT	-4- (5-chloropyrimidinyl)	-OCH	-H
ACU	-4- (5-chloropyrimidinyl)	-OCHCH	-H
				ACV	-4- (5-chloropyrimidinyl)	-OCF	-H
ACW	-4- (5-chloropyrimidinyl)	-tert-butyl	-H
				ACX	-4- (5-chloropyrimidinyl)	-isopropyl group	-H
ACY	-4- (5-chloropyrimidinyl)	-CH	-CH
				ACZ	-4- (5-chloropyrimidinyl)	-H	-H
ADA	-4- (5-chloropyrimidinyl)	-H	-Cl
				ADB	-4- (5-chloropyrimidinyl)	-H	-Br
ADC	-4- (5-chloropyrimidinyl)	-H	-F
				ADD	-4- (5-chloropyrimidinyl)	-H	-CH
ADE	-4- (5-chloropyrimidinyl)	-H	-CF
				ADF	-4- (5-chloropyrimidinyl)	-H	-OCH
ADG	-4- (5-chloropyrimidinyl)	-H	-OCHCH
				ADH	-4- (5-chloropyrimidinyl)	-H	-OCF
ADI	-4- (5-chloropyrimidinyl)	-H	-tert-butyl
				ADJ	-4- (5-chloropyrimidinyl)	-H	-isopropyl group
ADK	-4- (5-methylpyrimidinyl)	-Cl	-H
				ADL	-4- (5-methylpyrimidinyl)	-Br	-H
ADM	-4- (5-methylpyrimidinyl)	-F	-H
				ADN	-4- (5-methylpyrimidinyl)	-CH	-H
ADO	-4- (5-methylpyrimidinyl)	-CF	-H

ADP	-4- (5-methylpyrimidinyl)	-OCH	-H
				ADQ	-4- (5-methylpyrimidinyl)	-OCHCH	-H
ADR	-4- (5-methylpyrimidinyl)	-OCF	-H
				ADS	-4- (5-methylpyrimidinyl)	-tert-butyl	-H
ADT	-4- (5-methylpyrimidinyl)	-isopropyl group	-H
				ADU	-4- (5-methylpyrimidinyl)	-CH	-CH
ADV	-4- (5-methylpyrimidinyl)	-H	-H
				ADW	-4- (5-methylpyrimidinyl)	-H	-Cl
ADX	-4- (5-methylpyrimidinyl)	-H	-Br
				ADY	-4- (5-methylpyrimidinyl)	-H	-F
ADZ	-4- (5-methylpyrimidinyl)	-H	-CH
				AEA	-4- (5-methylpyrimidinyl)	-H	-CF
AEB	-4- (5-methylpyrimidinyl)	-H	-OCH
				AEC	-4- (5-methylpyrimidinyl)	-H	-OCHCH
AED	-4- (5-methylpyrimidinyl)	-H	-OCF
				AEE	-4- (5-methylpyrimidinyl)	-H	-tert-butyl
AEF	-4- (5-methylpyrimidinyl)	-H	-isopropyl group
				AEG	-2-pyrazinyl radical	-Cl	-H
AEH	-2-pyrazinyl radical	-Br	-H
				AEI	-2-pyrazinyl radical	-F	-H
AEJ	-2-pyrazinyl radical	-CH	-H
				AEK	-2-pyrazinyl radical	-CF	-H
AEL	-2-pyrazinyl radical	-OCH	-H
				AEM	-2-pyrazinyl radical	-OCHCH	-H
AEN	-2-pyrazinyl radical	-OCF	-H
				AEO	-2-pyrazinyl radical	-tert-butyl	-H
AEP	-2-pyrazinyl radical	-isopropyl group	-H

AEQ	-2-pyrazinyl radical	-CH	-CH
				AER	-2-pyrazinyl radical	-H	-H
AES	-2-pyrazinyl radical	-H	-Cl
				AET	-2-pyrazinyl radical	-H	-Br
AEU	-2-pyrazinyl radical	-H	-F
				AEV	-2-pyrazinyl radical	-H	-CH
AEW	-2-pyrazinyl radical	-H	-CF
				AEX	-2-pyrazinyl radical	-H	-OCH
AEY	-2-pyrazinyl radical	-H	-OCHCH
				AEZ	-2-pyrazinyl radical	-H	-OCF
AFA	-2-pyrazinyl radical	-H	-tert-butyl
				AFB	-2-pyrazinyl radical	-H	-isopropyl group
AFC	-2- (3-chloropyrazinyl)	-Cl	-H
				AFD	-2- (3-chloropyrazinyl)	-Br	-H
AFE	-2- (3-chloropyrazinyl)	-F	-H
				AFF	-2- (3-chloropyrazinyl)	-CH	-H
AFG	-2- (3-chloropyrazinyl)	-CF	-H
				AFH	-2- (3-chloropyrazinyl)	-OCH	-H
AFI	-2- (3-chloropyrazinyl)	-OCHCH	-H
				AFJ	-2- (3-chloropyrazinyl)	-OCF	-H
AFK	-2- (3-chloropyrazinyl)	-tert-butyl	-H
				AFL	-2- (3-chloropyrazinyl)	-isopropyl group	-H
AFM	-2- (3-chloropyrazinyl)	-CH	-CH
				AFN	-2- (3-chloropyrazinyl)	-H	-H
AFO	-2- (3-chloropyrazinyl)	-H	-Cl
				AFP	-2- (3-chloropyrazinyl)	-H	-Br
AFQ	-2- (3-chloropyrazinyl)	-H	-F

AFR	-2- (3-chloropyrazinyl)	-H	CH
				AFS	-2- (3-chloropyrazinyl)	-H	-CF
AFT	-2- (3-chloropyrazinyl)	-H	-OCH
				AFU	-2- (3-chloropyrazinyl)	-H	-OCHCH
AFV	-2- (3-chloropyrazinyl)	-H	-OCF
				AFW	-2- (3-chloropyrazinyl)	-H	-tert-butyl
AFX	-2- (3-chloropyrazinyl)	-H	-isopropyl group
				AFY	-2- (3-methylpyrazinyl)	-Cl	-H
AFZ	-2- (3-methylpyrazinyl)	-Br	-H
				AGA	-2- (3-methylpyrazinyl)	-F	-H
AGB	-2- (3-methylpyrazinyl)	-CH	-H
				AGC	-2- (3-methylpyrazinyl)	-CF	-H
AGD	-2- (3-methylpyrazinyl)	-OCH	-H
				AGE	-2- (3-methylpyrazinyl)	-OCHCH	-H
AGF	-2- (3-methylpyrazinyl)	-OCF	-H
				AGG	-2- (3-methylpyrazinyl)	-tert-butyl	-H
AGH	-2- (3-methylpyrazinyl)	-isopropyl group	-H
				AGI	-2- (3-methylpyrazinyl)	-CH	-CH
AGJ	-2- (3-methylpyrazinyl)	-H	-H
				AGK	-2- (3-methylpyrazinyl)	-H	-Cl
AGL	-2- (3-methylpyrazinyl)	-H	-Br
				AGM	-2- (3-methylpyrazinyl)	-H	-F
AGN	-2- (3-methylpyrazinyl)	-H	-CH
				AGO	-2- (3-methylpyrazinyl)	-H	-CF
AGP	-2- (3-methylpyrazinyl)	-H	-OCH
				AGQ	-2- (3-methylpyrazinyl)	-H	-OCHCH
AGR	-2- (3-methylpyrazinyl)	-H	-OCF

AGS	-2- (3-methylpyrazinyl)	-H	-tert-butyl
				AGT	-2- (3-methylpyrazinyl)	-H	-isopropyl group
AGU	-2-pyridazinyl radical	-Cl	-H
				AGV	-2-pyridazinyl radical	-Br	-H
AGW	-2-pyridazinyl radical	-F	-H
				AGX	-2-pyridazinyl radical	-CH	-H
AGY	-2-pyridazinyl radical	-CF	-H
				AGZ	-2-pyridazinyl radical	-OCH	-H
AHA	-2-pyridazinyl radical	-OCHCH	-H
				AHB	-2-pyridazinyl radical	-OCF	-H
AHC	-2-pyridazinyl radical	-tert-butyl	-H
				AHD	-2-pyridazinyl radical	-isopropyl group	-H
AHE	-2-pyridazinyl radical	-CH	-CH
				AHF	-2-pyridazinyl radical	-H	-H
AHG	-2-pyridazinyl radical	-H	-Cl
				AHH	-2-pyridazinyl radical	-H	-Br
AHI	-2-pyridazinyl radical	-H	-F
				AHJ	-2-pyridazinyl radical	-H	-CH
AHK	-2-pyridazinyl radical	-H	-CF
				AHL	-2-pyridazinyl radical	-H	-OCH
AHM	-2-pyridazinyl radical	-H	-OCHCH
				AHN	-2-pyridazinyl radical	-H	-OCF
AHO	-2-pyridazinyl radical	-H	-tert-butyl
				AHP	-2-pyridazinyl radical	-H	-isopropyl group
AHQ	-3- (4-chloropyridazinyl)	-Cl	-H
				AHR	-3- (4-chloropyridazinyl)	-Br	-H
AHS	-3- (4-chloropyridazinyl)	-F	-H

AHT	-3- (4-chloropyridazinyl)	-CH	-H
				AHU	-3- (4-chloropyridazinyl)	-CF	-H
AHV	-3- (4-chloropyridazinyl)	-OCH	-H
				AHW	-3- (4-chloropyridazinyl)	-OCHCH	-H
AHX	-3- (4-chloropyridazinyl)	-OCF	-H
				AHY	-3- (4-chloropyridazinyl)	-tert-butyl	-H
AHZ	-3- (4-chloropyridazinyl)	-isopropyl group	-H
				AIA	-3- (4-chloropyridazinyl)	-CH	-CH
AIB	-3- (4-chloropyridazinyl)	-H	-H
				AIC	-3- (4-chloropyridazinyl)	-H	-Cl
AID	-3- (4-chloropyridazinyl)	-H	-Br
				AIE	-3- (4-chloropyridazinyl)	-H	-F
AIF	-3- (4-chloropyridazinyl)	-H	-CH
				AIG	-3- (4-chloropyridazinyl)	-H	-CF
AIH	-3- (4-chloropyridazinyl)	-H	-OCH
				AII	-3- (4-chloropyridazinyl)	-H	-OCHCH
AIJ	-3- (4-chloropyridazinyl)	-H	-OCF
				AIK	-3- (4-chloropyridazinyl)	-H	-tert-butyl
AIL	-3- (4-chloropyridazinyl)	-H	-isopropyl group
				AIM	-3- (4-methylpyridazinyl)	-Cl	-H
AIN	-3- (4-methylpyridazinyl)	-Br	-H
				AIO	-3-(4-Pyridazinyl methyl	-F	-H
AIP	-3- (4-methylpyridazinyl)	-CH	-H
				AIQ	-3- (4-methylpyridazinyl)	-CF	-H
AIR	-3- (4-methylpyridazinyl)	-OCH	-H
				AIS	-3- (4-methylpyridazinyl)	-OCHCH	-H
AIT	-3- (4-methylpyridazinyl)	-OCF	-H

AIU	-3- (4-methylpyridazinyl)	-tert-butyl	H
				AIV	-3- (4-methylpyridazinyl)	-isopropyl group	-H
AIW	-3- (4-methylpyridazinyl)	-CH	-CH
				AIX	-3- (4-methylpyridazinyl)	-H	-H
AIY	-3- (4-methylpyridazinyl)	-H	-Cl
				AIZ	-3- (4-methylpyridazinyl)	-H	-Br
AJA	-3- (4-methylpyridazinyl)	-H	-F
				AJB	-3- (4-methylpyridazinyl)	-H	-CH
AJC	-3- (4-methylpyridazinyl)	-H	-CF
				AJD	-3- (4-methylpyridazinyl)	-H	-OCH
AJE	-3- (4-methylpyridazinyl)	-H	-OCHCH
				AJF	-3- (4-methylpyridazinyl)	-H	-OCF
AJG	-3- (4-methylpyridazinyl)	-H	-tert-butyl
				AJH	-3- (4-methylpyridazinyl)	-H	-isopropyl group
AJI	-4-thiazanyl	-Cl	-H
				AJJ	-4-thiazanyl	-Br	-H
AJK	-4-thiazanyl	-F	-H
				AJL	-4-thiazanyl	-CH	-H
AJM	-4-thiazanyl	-CF	-H
				AJN	-4-thiazanyl	-OCH	-H
AJO	-4-thiazanyl	-OCHCH	-H
				AJP	-4-thiazanyl	-OCF	-H
AJQ	-4-thiazanyl	-tert-butyl	-H
				AJR	-4-thiazanyl	-isopropyl group	-H
AJS	-4-thiazanyl	-CH	-CH
				AJT	-4-thiazanyl	-H	-H
AJU	-4-thiazanyl	-H	-Cl
				AJV	-4-thiazanyl	-H	-Br
AJW	-4-thiazanyl	-H	-F

AJX	-4-thiazanyl	-H	-CH
				AJY	-4-thiazanyl	-H	-CF
AJZ	-4-thiazanyl	-H	-OCH
				AKA	-4-thiazanyl	-H	-OCHCH
AKB	-4-thiazanyl	-H	-OCF
				AKC	-4-thiazanyl	-H	-tert-butyl
AKD	-4-thiazanyl	-H	-isopropyl group
				AKE	-5- (4-chloro-thiazanyl)	-Cl	-H
AKF	-5- (4-chloro-thiazanyl)	-Br	-H
				AKG	-5- (4-chloro-thiazanyl)	-F	-H
AKH	-5- (4-chloro-thiazanyl)	-CH	-H
				AKI	-5- (4-chloro-thiazanyl)	-CF	-H
AKJ	-5- (4-chloro-thiazanyl)	-OCH	-H
				AKK	-5- (4-chloro-thiazanyl)	-OCHCH	-H
AKL	-5- (4-chloro-thiazanyl)	-OCF	-H
				AKM	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
AKN	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
				AKO	-5- (4-chloro-thiazanyl)	-CH	-CH
AKP	-5- (4-chloro-thiazanyl)	-H	-H
				AKQ	-5- (4-chloro-thiazanyl)	-H	-Cl
AKR	-5- (4-chloro-thiazanyl)	-H	-Br
				AKS	-5- (4-chloro-thiazanyl)	-H	-F
AKT	-5- (4-chloro-thiazanyl)	-H	-CH
				AKU	-5- (4-chloro-thiazanyl)	-H	-CF
AKV	-5- (4-chloro-thiazanyl)	-H	-OCH
				AKW	-5- (4-chloro-thiazanyl)	-H	-OCHCH
AKX	-5- (4-chloro-thiazanyl)	-H	-OCF
				AKY	-5- (4-chloro-thiazanyl)	-H	-tert-butyl

AKZ	-5- (4-chloro-thiazanyl)	-H	-isopropyl group
				ALA	-5- (4-methylthiozanyl)	-Cl	-H
ALB	-5- (4-methylthiozanyl)	-Br	-H
				ALC	-5- (4-methylthiozanyl)	-F	-H
ALD	-5- (4-methylthiozanyl)	-CH	-H
				ALE	-5- (4-methylthiozanyl)	-CF	-H
ALF	-5- (4-methylthiozanyl)	-OCH	-H
				ALG	-5- (4-methylthiozanyl)	-OCHCH	-H
ALH	-5- (4-methylthiozanyl)	-OCF	-H
				ALI	-5- (4-methylthiozanyl)	-tert-butyl	-H
ALJ	-5- (4-methylthiozanyl)	-isopropyl group	-H
				ALK	-5- (4-methylthiozanyl)	-CH	-CH
ALL	-5- (4-methylthiozanyl)	-H	-H
				ALM	-5- (4-methylthiozanyl)	-H	-Cl
ALN	-5- (4-methylthiozanyl)	-H	-Br
				ALO	-5- (4-methylthiozanyl)	-H	-F
ALP	-5- (4-methylthiozanyl)	-H	-CH
				ALQ	-5- (4-methylthiozanyl)	-H	-CF
ALR	-5- (4-methylthiozanyl)	-H	-OCH
				ALS	-5- (4-methylthiozanyl)	-H	-OCHCH
ALT	-5- (4-methylthiozanyl)	-H	-OCF
				ALU	-5- (4-methylthiozanyl)	-H	-tert-butyl
ALV	-5- (4-methylthiozanyl)	-H	-isopropyl group

TABLE II

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				ALW	-2- (3-chloropyridyl)	-Cl	-H
ALX	-2- (3-chloropyridyl)	-Br	-H
				ALY	-2- (3-chloropyridyl)	-F	-H
ALZ	-2- (3-chloropyridyl)	-CH	-H
				AMA	-2- (3-chloropyridyl)	-CF	-H
AMB	-2- (3-chloropyridyl)	-OCH	-H
				AMC	-2- (3-chloropyridyl)	-OCHCH	-H
AMD	-2- (3-chloropyridyl)	-OCF	-H
				AME	-2- (3-chloropyridyl)	-tert-butyl	-H
AMF	-2- (3-chloropyridyl)	-isopropyl group	-H
				AMG	-2- (3-chloropyridyl)	-CH	-CH
AMH	-2- (3-chloropyridyl)	-H	-H
				AMI	-2- (3-chloropyridyl)	-H	-Cl
AMJ	-2- (3-chloropyridyl)	-H	-Br
				AMK	-2- (3-chloropyridyl)	-H	-F
AML	-2- (3-chloropyridyl)	-H	-CH
				AMM	-2- (3-chloropyridyl)	-H	-CF
AMN	-2- (3-chloropyridyl)	-H	-OCH

AMO	-2- (3-chloropyridyl)	-H	-OCHCH
				AMP	-2- (3-chloropyridyl)	-H	-OCF
AMQ	-2- (3-chloropyridyl)	-H	-tert-butyl
				AMR	-2- (3-chloropyridyl)	-H	-isopropyl group
AMS	-2- (3-methylpyridinyl)	-Cl	-H
				AMT	-2- (3-methylpyridinyl)	-Br	-H
AMU	-2- (3-methylpyridinyl)	-F	-H
				AMV	-2- (3-methylpyridinyl)	-CH	-H
AMW	-2- (3-methylpyridinyl)	-CF	-H
				AMX	-2- (3-methylpyridinyl)	-OCH	-H
AMY	-2- (3-methylpyridinyl)	-OCHCH	-H
				AMZ	-2- (3-methylpyridinyl)	-OCF	-H
ANA	-2- (3-methylpyridinyl)	-tert-butyl	-H
				ANB	-2- (3-methylpyridinyl)	-isopropyl group	-H
ANC	-2- (3-methylpyridinyl)	-CH	-CH
				AND	-2- (3-methylpyridinyl)	-H	-H
ANE	-2- (3-methylpyridinyl)	-H	-Cl
				ANF	-2- (3-methylpyridinyl)	-H	-Br
ANG	-2- (3-methylpyridinyl)	-H	-F
				ANH	-2- (3-methylpyridinyl)	-H	-CH
ANI	-2- (3-methylpyridinyl)	-H	-CF
				ANJ	-2- (3-methylpyridinyl)	-H	-OCH
ANK	-2- (3-methylpyridinyl)	-H	-OCHCH
				ANL	-2- (3-methylpyridinyl)	-H	-OCF
ANM	-2- (3-methylpyridinyl)	-H	-tert-butyl
				ANN	-2- (3-methylpyridinyl)	-H	-isopropyl group
ANO	-2-(3-CF-pyridyl group)	-Cl	-H

ANP	-2-(3-CF-pyridyl group)	-Br	-H
				ANQ	-2-(3-CF-pyridyl group)	-F	-H
ANR	-2-(3-CF-pyridyl group)	-CH	-H
				ANS	-2-(3-CF-pyridyl group)	-CF	-H
ANT	-2-(3-CF-pyridyl group)	-OCH	-H
				ANU	-2-(3-CF-pyridyl group)	-OCHCH	-H
ANV	-2-(3-CF-pyridyl group)	-OCF	-H
				ANW	-2-(3-CF-pyridyl group)	-tert-butyl	-H
ANX	-2-(3-CF-pyridyl group)	-isopropyl group	-H
				ANY	-2-(3-CF-pyridyl group)	-CH	-CH
ANZ	-2-(3-CF-pyridyl group)	-H	-H
				AOA	-2-(3-CF-pyridyl group)	-H	-Cl
AOB	-2-(3-CF-pyridyl group)	-H	-Br
				AOC	-2-(3-CF-pyridyl group)	-H	-F
AOD	-2-(3-CF-pyridyl group)	-H	-CH
				AOE	-2-(3-CF-pyridyl group)	-H	-CF
AOF	-2-(3-CF-pyridyl group)	-H	-OCH
				AOG	-2-(3-CF-pyridyl group)	-H	-OCHCH
AOH	-2-(3-CF-pyridyl group)	-H	-OCF
				AOI	-2-(3-CF-pyridyl group)	-H	-tert-butyl
AOJ	-2-(3-CF-pyridyl group)	-H	-isopropyl group
				AOK	-4- (5-chloropyrimidinyl)	-Cl	-H
AOL	-4- (5-chloropyrimidinyl)	-Br	-H
				AOM	-4- (5-chloropyrimidinyl)	-F	-H
AON	-4- (5-chloropyrimidinyl)	-CH	-H
				AOO	-4- (5-chloropyrimidinyl)	-CF	-H
AOP	-4- (5-chloropyrimidinyl)	-OCH	-H

AOQ	-4- (5-chloropyrimidinyl)	-OCHCH	-H
				AOR	-4- (5-chloropyrimidinyl)	-OCF	-H
AOS	-4- (5-chloropyrimidinyl)	-tert-butyl	-H
				AOT	-4- (5-chloropyrimidinyl)	-isopropyl group	-H
AOU	-4- (5-chloropyrimidinyl)	-CH	-CH
				AOV	-4- (5-chloropyrimidinyl)	-H	-H
AOW	-4- (5-chloropyrimidinyl)	-H	-Cl
				AOX	-4- (5-chloropyrimidinyl)	-H	-Br
AOY	-4- (5-chloropyrimidinyl)	-H	-F
				AOZ	-4- (5-chloropyrimidinyl)	-H	-CH
APA	-4- (5-chloropyrimidinyl)	-H	-CF
				APB	-4- (5-chloropyrimidinyl)	-H	-OCH
APC	-4- (5-chloropyrimidinyl)	-H	-OCHCH
				APD	-4- (5-chloropyrimidinyl)	-H	-OCF
APE	-4- (5-chloropyrimidinyl)	-H	-tert-butyl
				APF	-4- (5-chloropyrimidinyl)	-H	-isopropyl group
APG	-4- (5-methylpyrimidinyl)	-Cl	-H
				APH	-4- (5-methylpyrimidinyl)	-Br	-H
API	-4- (5-methylpyrimidinyl)	-F	-H
				APJ	-4- (5-methylpyrimidinyl)	-CH	-H
APK	-4- (5-methylpyrimidinyl)	-CF	-H
				APL	-4- (5-methylpyrimidinyl)	-OCH	-H
APM	-4- (5-methylpyrimidinyl)	-OCHCH	-H
				APN	-4- (5-methylpyrimidinyl)	-OCF	-H
APO	-4- (5-methylpyrimidinyl)	-tert-butyl	-H
				APP	-4- (5-methylpyrimidinyl)	-isopropyl group	-H
APQ	-4- (5-methylpyrimidinyl)	-CH	-CH

APR	-4- (5-methylpyrimidinyl)	-H	-H
				APS	-4- (5-methylpyrimidinyl)	-H	-Cl
APT	-4- (5-methylpyrimidinyl)	-H	-Br
				APU	-4- (5-methylpyrimidinyl)	-H	-F
APV	-4- (5-methylpyrimidinyl)	-H	-CH
				APW	-4- (5-methylpyrimidinyl)	-H	-CF
APX	-4- (5-methylpyrimidinyl)	-H	-OCH
				APY	-4- (5-methylpyrimidinyl)	-H	-OCHCH
APZ	-4- (5-methylpyrimidinyl)	-H	-OCF
				AQA	-4- (5-methylpyrimidinyl)	-H	-tert-butyl
AQB	-4- (5-methylpyrimidinyl)	-H	-isopropyl group
				AQC	-2-pyrazinyl radical	-Cl	-H
AQD	-2-pyrazinyl radical	-Br	-H
				AQE	-2-pyrazinyl radical	-F	-H
AQF	-2-pyrazinyl radical	-CH	-H
				AQG	-2-pyrazinyl radical	-CF	-H
AQH	-2-pyrazinyl radical	-OCH	-H
				AQI	-2-pyrazinyl radical	-OCHCH	-H
AQJ	-2-pyrazinyl radical	-OCF	-H
				AQK	-2-pyrazinyl radical	-tert-butyl	-H
AQL	-2-pyrazinyl radical	-isopropyl group	-H
				AQM	-2-pyrazinyl radical	-CH	-CH
AQN	-2-pyrazinyl radical	-H	-H
				AQO	-2-pyrazinyl radical	-H	-Cl
AQP	-2-pyrazinyl radical	-H	-Br
				AQQ	-2-pyrazinyl radical	-H	-F
AQR	-2-pyrazinyl radical	-H	-CH

AQS	-2-pyrazinyl radical	-H	-CF
				AQT	-2-pyrazinyl radical	-H	-OCH
AQU	-2-pyrazinyl radical	-H	-OCHCH
				AQV	-2-pyrazinyl radical	-H	-OCF
AQW	-2-pyrazinyl radical	-H	-tert-butyl
				AQX	-2-pyrazinyl radical	-H	-isopropyl group
AQY	-2- (3-chloropyrazinyl)	-Cl	-H
				AQZ	-2- (3-chloropyrazinyl)	-Br	-H
ARA	-2- (3-chloropyrazinyl)	-F	-H
				ARB	-2- (3-chloropyrazinyl)	-CH	-H
ARC	-2- (3-chloropyrazinyl)	-CF	-H
				ARD	-2- (3-chloropyrazinyl)	-OCH	-H
ARE	-2- (3-chloropyrazinyl)	-OCHCH	-H
				ARF	-2- (3-chloropyrazinyl)	-OCF	-H
ARG	-2- (3-chloropyrazinyl)	-tert-butyl	-H
				ARH	-2- (3-chloropyrazinyl)	-isopropyl group	-H
ARI	-2- (3-chloropyrazinyl)	-CH	-CH
				ARJ	-2- (3-chloropyrazinyl)	-H	-H
ARK	-2- (3-chloropyrazinyl)	-H	-Cl
				ARL	-2- (3-chloropyrazinyl)	-H	-Br
ARM	-2- (3-chloropyrazinyl)	-H	-F
				ARN	-2- (3-chloropyrazinyl)	-H	-CH
ARO	-2- (3-chloropyrazinyl)	-H	-CF
				ARP	-2- (3-chloropyrazinyl)	-H	-OCH
ARQ	-2- (3-chloropyrazinyl)	-H	-OCHCH
				ARR	-2- (3-chloropyrazinyl)	-H	-OCF
ARS	-2- (3-chloropyrazinyl)	-H	-tert-butyl

ART	-2- (3-chloropyrazinyl)	-H	-isopropyl group
				ARU	-2- (3-methylpyrazinyl)	-Cl	-H
ARV	-2- (3-methylpyrazinyl)	-Br	-H
				ARW	-2- (3-methylpyrazinyl)	-F	-H
ARX	-2- (3-methylpyrazinyl)	-CH	-H
				ARY	-2- (3-methylpyrazinyl)	-CF	-H
ARZ	-2- (3-methylpyrazinyl)	-OCH	-H
				ASA	-2- (3-methylpyrazinyl)	-OCHCH	-H
ASB	-2- (3-methylpyrazinyl)	-OCF	-H
				ASC	-2- (3-methylpyrazinyl)	-tert-butyl	-H
ASD	-2- (3-methylpyrazinyl)	-isopropyl alcoholBase of	-H
				ASE	-2- (3-methylpyrazinyl)	-CH	-CH
ASF	-2- (3-methylpyrazinyl)	-H	-H
				ASG	-2- (3-methylpyrazinyl)	-H	-Cl
ASH	-2- (3-methylpyrazinyl)	-H	-Br
				ASI	-2- (3-methylpyrazinyl)	-H	-F
ASJ	-2- (3-methylpyrazinyl)	-H	-CH
				ASK	-2- (3-methylpyrazinyl)	-H	-CF
ASL	-2- (3-methylpyrazinyl)	-H	-OCH
				ASM	-2- (3-methylpyrazinyl)	-H	-OCHCH
ASN	-2- (3-methylpyrazinyl)	-H	-OCF
				ASO	-2- (3-methylpyrazinyl)	-H	-tert-butyl
ASP	-2- (3-methylpyrazinyl)	-H	-isopropyl group
				ASQ	-2-pyridazinyl radical	-Cl	-H
ASR	-2-pyridazinyl radical	-Br	-H
				ASS	-2-pyridazinyl radical	-F	-H
AST	-2-pyridazinyl radical	-CH	-H

ASU	-2-pyridazinyl radical	-CF	-H
				ASV	-2-pyridazinyl radical	-OCH	-H
ASW	-2-pyridazinyl radical	-OCHCH	-H
				ASX	-2-pyridazinyl radical	-OCF	-H
ASY	-2-pyridazinyl radical	-tert-butyl	-H
				ASZ	-2-pyridazinyl radical	-isopropyl group	-H
ATA	-2-pyridazinyl radical	-CH	-CH
				ATB	-2-pyridazinyl radical	-H	-H
ATC	-2-pyridazinyl radical	-H	-Cl
				ATD	-2-pyridazinyl radical	-H	-Br
ATE	-2-pyridazinyl radical	-H	-F
				ATF	-2-pyridazinyl radical	-H	-CH
ATG	-2-pyridazinyl radical	-H	-CF
				ATH	-2-pyridazinyl radical	-H	-OCH
ATI	-2-pyridazinyl radical	-H	-OCHCH
				ATJ	-2-pyridazinyl radical	-H	-OCF
ATK	-2-pyridazinyl radical	-H	-tert-butyl
				ATL	-2-pyridazinyl radical	-H	-isopropyl group
ATM	-3- (4-chloropyridazinyl)	-Cl	-H
				ATN	-3- (4-chloropyridazinyl)	-Br	-H
ATO	-3- (4-chloropyridazinyl)	-F	-H
				ATP	-3- (4-chloropyridazinyl)	-CH	-H
ATQ	-3- (4-chloropyridazinyl)	-CF	-H
				ATR	-3- (4-chloropyridazinyl)	-OCH	-H
ATS	-3- (4-chloropyridazinyl)	-OCHCH	-H
				ATT	-3- (4-chloropyridazinyl)	-OCF	-H
ATU	-3- (4-chloropyridazinyl)	-tert-butyl	-H

ATV	-3- (4-chloropyridazinyl)	-isopropyl group	-H
				ATW	-3- (4-chloropyridazinyl)	-CH	-CH
ATX	-3- (4-chloropyridazinyl)	-H	-H
				ATY	-3- (4-chloropyridazinyl)	-H	-Cl
ATZ	-3- (4-chloropyridazinyl)	-H	-Br
				AUA	-3- (4-chloropyridazinyl)	-H	-F
AUB	-3- (4-chloropyridazinyl)	-H	-CH
				AUC	-3- (4-chloropyridazinyl)	-H	-CF
AUD	-3- (4-chloropyridazinyl)	-H	-OCH
				AUE	-3- (4-chloropyridazinyl)	-H	-OCHCH
AUF	-3- (4-chloropyridazinyl)	-H	-OCF
				AUG	-3- (4-chloropyridazinyl)	-H	-tert-butyl
AUH	-3- (4-chloropyridazinyl)	-H	-isopropyl group
				AUI	-3- (4-methylpyridazinyl)	-Cl	-H
AUJ	-3- (4-methylpyridazinyl)	-Br	-H
				AUK	-3- (4-methylpyridazinyl)	-F	-H
AUL	-3- (4-methylpyridazinyl)	-CH	-H
				AUM	-3- (4-methylpyridazinyl)	-CF	-H
AUN	-3- (4-methylpyridazinyl)	-OCH	-H
				AUO	-3- (4-methylpyridazinyl)	-OCHCH	-H
AUP	-3- (4-methylpyridazinyl)	-OCF	-H
				AUQ	-3- (4-methylpyridazinyl)	-tert-butyl	-H
AUR	-3- (4-methylpyridazinyl)	-isopropyl group	-H
				AUS	-3- (4-methylpyridazinyl)	-CH	-CH
AUT	-3- (4-methylpyridazinyl)	-H	-H
				AUU	-3- (4-methylpyridazinyl)	-H	-Cl
AUV	-3- (4-methylpyridazinyl)	-H	-Br

AUW	-3- (4-methylpyridazinyl)	-H	-F
				AUX	-3- (4-methylpyridazinyl)	-H	-CH
AUY	-3- (4-methylpyridazinyl)	-H	-CF
				AUZ	-3- (4-methylpyridazinyl)	-H	-OCH
AVA	-3- (4-methylpyridazinyl)	-H	-OCHCH
				AVB	-3- (4-methylpyridazinyl)	-H	-OCF
AVC	-3- (4-methylpyridazinyl)	-H	-tert-butyl
				AVD	-3- (4-methylpyridazinyl)	-H	-isopropyl group
AVE	-4-thiazanyl	-Cl	-H
				AVF	-4-thiazanyl	-Br	-H
AVG	-4-thiazanyl	-F	-H
				AVH	-4-thiazanyl	-CH	-H
AVI	-4-thiazanyl	-CF	-H
				AVJ	-4-thiazanyl	-OCH	-H
AVK	-4-thiazanyl	-OCHCH	-H
				AVL	-4-thiazanyl	-OCF	-H
AVM	-4-thiazanyl	-tert-butyl	-H
				AVN	-4-thiazanyl	-isopropyl group	-H
AVO	-4-thiazanyl	-CH	-CH
				AVP	-4-thiazanyl	-H	-H
AVQ	-4-thiazanyl	-H	-Cl
				AVR	-4-thiazanyl	-H	-Br
AVS	-4-thiazanyl	-H	-F
				AVT	-4-thiazanyl	-H	-CH
AVU	-4-thiazanyl	-H	-CF
				AVV	-4-thiazanyl	-H	-OCH
AVW	-4-thiazanyl	-H	-OCHCH
				AVX	-4-thiazanyl	-H	-OCF
AVY	-4-thiazanyl	-H	-tert-butyl

AVZ	-4-thiazanyl	-H	-isopropyl group
				AWA	-5- (4-chloro-thiazanyl)	-Cl	-H
AWB	-5- (4-chloro-thiazanyl)	-Br	-H
				AWC	-5- (4-chloro-thiazanyl)	-F	-H
AWD	-5- (4-chloro-thiazanyl)	-CH	-H
				AWE	-5- (4-chloro-thiazanyl)	-CF	-H
AWF	-5- (4-chloro-thiazanyl)	-OCH	-H
				AWG	-5- (4-chloro-thiazanyl)	-OCHCH	-H
AWH	-5- (4-chloro-thiazanyl)	-OCF	-H
				AWI	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
AWJ	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
				AWK	-5- (4-chloro-thiazanyl)	-CH	-CH
AWL	-5- (4-chloro-thiazanyl)	-H	-H
				AWM	-5- (4-chloro-thiazanyl)	-H	-Cl
AWN	-5- (4-chloro-thiazanyl)	-H	-Br
				AWO	-5- (4-chloro-thiazanyl)	-H	-F
AWP	-5- (4-chloro-thiazanyl)	-H	-CH
				AWQ	-5- (4-chloro-thiazanyl)	-H	-CF
AWR	-5- (4-chloro-thiazanyl)	-H	-OCH
				AWS	-5- (4-chloro-thiazanyl)	-H	-OCHCH
AWT	-5- (4-chloro-thiazanyl)	-H	-OCF
				AWU	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
AWV	-5- (4-chloro-thiazanyl)	-H	-isopropyl group
				AWW	-5- (4-methylthiozanyl)	-Cl	-H
AWX	-5- (4-methylthiozanyl)	-Br	-H
				AWY	-5- (4-methylthiozanyl)	-F	-H
AWZ	-5- (4-methylthiozanyl)	-CH	-H

AXA	-5- (4-methylthiozanyl)	-CF	-H
				AXB	-5- (4-methylthiozanyl)	-OCH	-H
AXC	-5- (4-methylthiozanyl)	-OCHCH	-H
				AXD	-5- (4-methylthiozanyl)	-OCF	-H
AXE	-5- (4-methylthiozanyl)	-tert-butyl	-H
				AXF	-5- (4-methylthiozanyl)	-isopropyl group	-H
AXG	-5- (4-methylthiozanyl)	-CH	-CH
				AXH	-5- (4-methylthiozanyl)	-H	-H
AXI	-5- (4-methylthiozanyl)	-H	-Cl
				AXJ	-5- (4-methylthiozanyl)	-H	-Br
AXK	-5- (4-methylthiozanyl)	-H	-F
				AXL	-5- (4-methyl tjiazanyl)	-H	-CH
AXM	-5- (4-methylthiozanyl)	-H	-CF
				AXN	-5- (4-methylthiozanyl)	-H	-OCH
AXO	-5- (4-methylthiozanyl)	-H	-OCHCH
				AXP	-5- (4-methylthiozanyl)	-H	-OCF
AXQ	-5- (4-methylthiozanyl)	-H	-tert-butyl
				AXR	-5- (4-methylthiozanyl)	-H	-isopropyl group

TABLE III

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				AXS (a, b and c)	-2- (3-chloropyridyl)	-Cl	-H
AXT (a, b and c)	-2- (3-chloropyridyl)	-Br	-H
				AXU (a, b and c)	-2- (3-chloropyridyl)	-F	-H
AXV (a, b and c)	-2- (3-chloropyridyl)	-CH	-H
				AXW (a, b and c)	-2- (3-chloropyridyl)	-CF	-H
AXX (a, b and c)	-2- (3-chloropyridyl)	-OCH	-H
				AXY (a, b and c)	-2- (3-chloropyridyl)	-OCHCH	-H
AXZ (a, b and c)	-2- (3-chloropyridyl)	-OCF	-H
				AYA (a, b and c)	-2- (3-chloropyridyl)	-tert-butyl	-H
AYB (a, b and c)	-2- (3-chloropyridyl)	-isopropyl group	-H
				AYC (a, b and c)	-2- (3-chloropyridyl)	-CH	-CH
AYD (a, b and c)	-2- (3-chloropyridyl)	-H	-H
				AYE (a, b and c)	-2- (3-chloropyridyl)	-H	-Cl
AYF (a, b and c)	-2- (3-chloropyridyl)	-H	-Br
				AYG (a, b and c)	-2- (3-chloro)Pyridyl group)	-H	-F
AYH (a, b and c)	-2- (3-chloropyridyl)	-H	-CH

AYI (a, b and c)	-2- (3-chloropyridyl)	-H	-CF
				AYJ (a, b and c)	-2- (3-chloropyridyl)	-H	-OCH
AYK (a, b and c)	-2- (3-chloropyridyl)	-H	-OCHCH
				AYL (a, b and c)	-2- (3-chloropyridyl)	-H	-OCF
AYM (a, b and c)	-2- (3-chloropyridyl)	-H	-tert-butyl
				AYN (a, b and c)	-2- (3-chloropyridyl)	-H	-isopropyl group
AYO (a, b and c)	-2- (3-methylpyridinyl)	-Cl	-H
				AYP (a, b and c)	-2- (3-methylpyridinyl)	-Br	-H
AYQ (a, b and c)	-2- (3-methylpyridinyl)	-F	-H
				AYR (a, b and c)	-2- (3-methylpyridinyl)	-CH	-H
AYS (a, b and c)	-2- (3-methylpyridinyl)	-CF	-H
				AYT (a, b and c)	-2- (3-methylpyridinyl)	-OCH	-H
AYU (a, b and c)	-2- (3-methylpyridinyl)	-OCHCH	-H
				AYV (a, b and c)	-2- (3-methylpyridinyl)	-OCF	-H
AYW (a, b and c)	-2- (3-methylpyridinyl)	-tert-butyl	-H
				AYX (a, b and c)	-2- (3-methylpyridinyl)	-isopropyl group	-H
AYY (a, b and c)	-2- (3-methylpyridinyl)	-CH	-CH
				AYZ (a, b and c)	-2- (3-methylpyridinyl)	-H	-H
AZA (a, b and c)	-2- (3-methylpyridinyl)	-H-	Cl
				AZB (a, b and c)	-2- (3-methylpyridinyl)	-H	-Br
AZC (a, b and c)	-2- (3-methylpyridinyl)	-H	-F
				AZD (a, b and c)	-2- (3-methylpyridinyl)	-H	-CH
AZE (a, b and c)	-2- (3-methylpyridinyl)	-H	-CF
				AZF (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCH
AZG (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCHCH
				AZH (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCF
AZI (a, b and c)	-2- (3-methylpyridinyl)	-H	-tert-butyl

AZJ (a, b and c)	-2- (3-methylpyridinyl)	-H	-isopropyl group
				AZK (a, b and c)	-2-(3-CF-pyridyl group)	-Cl	-H
AZL (a, b and c)	-2-(3-CF-pyridyl group)	-Br	-H
				AZM (a, b and c)	-2-(3-CF-pyridyl group)	-F	-H
AZN (a, b and c)	-2-(3-CF-pyridyl group)	-CH	-H
				AZO (a, b and c)	-2-(3-CF-pyridyl group)	-CF	-H
AZP (a, b and c)	-2-(3-CF-pyridyl group)	-OCH	-H
				AZQ (a, b and c)	-2-(3-CF-pyridyl group)	-OCHCH	-H
AZR (a, b and c)	-2-(3-CF-pyridyl group)	-OCF	-H
				AZS (a, b and c)	-2-(3-CF-pyridyl group)	-tert-butyl	-H
AZT (a, b and c)	-2-(3-CF-pyridyl group)	-isopropyl group	-H
				AZU (a, b and c)	-2-(3-CF-pyridyl group)	-CH	-CH
AZV (a, b and c)	-2-(3-CF-pyridyl group)	-H	-H
				AZW (a, b and c)	-2-(3-CF-pyridyl group)	-H	-Cl
AZX (a, b and c)	-2-(3-CF-pyridyl group)	-H	-Br
				AZY (a, b and c)	-2-(3-CF-pyridyl group)	-H	-F
AZZ (a, b and c)	-2-(3-CF-pyridyl group)	-H	-CH
				BAA (a, b and c)	-2-(3-CF-pyridyl group)	-H	-CF
BAB (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCH
				BAC (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCHCH
BAD (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCF
				BAE (a, b and c)	-2-(3-CF-pyridyl group)	-H	-tert-butyl
BAF (a, b and c)	-2-(3-CF-pyridyl group)	-H	-isopropyl group
				BAG (a, b and c)	-4- (5-chloropyrimidinyl)	-Cl	-H
BAH (a, b and c)	-4- (5-chloropyrimidinyl)	-Br	-H
				BAI (a, b and c)	-4- (5-chloropyrimidinyl)	-F	-H
BAJ (a, b and c)	-4- (5-chloropyrimidinyl)	-CH	-H

BAK (a, b and c)	-4- (5-chloropyrimidinyl)	-CF	-H
				BAL (a, b and c)	-4- (5-chloropyrimidinyl)	-OCH	-H
BAM (a, b and c)	-4- (5-chloropyrimidinyl)	-OCHCH	-H
				BAN (a, b and c)	-4- (5-chloropyrimidinyl)	-OCF	-H
BAO (a, b and c)	-4- (5-chloropyrimidinyl)	-tert-butyl	-H
				BAP (a, b and c)	-4- (5-chloropyrimidinyl)	-isopropyl group	-H
BAQ (a, b and c)	-4- (5-chloropyrimidinyl)	-CH	-CH
				BAR (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-H
BAS (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-Cl
				BAT (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-Br
BAU (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-F
				BAV (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-CH
BAW (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-CF
				BAX (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCH
BAY (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCHCH
				BAZ (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCF
BBA (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-tert-butyl
				BBB (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-isopropyl group
BBC (a, b and c)	-4- (5-methylpyrimidinyl)	-Cl	-H
				BBD (a, b and c)	-4- (5-methylpyrimidinyl)	-Br	-H
BBE (a, b and c)	-4- (5-methylpyrimidinyl)	-F	-H
				BBF (a, b and c)	-4- (5-methylpyrimidinyl)	-CH	-H
BBG (a, b and c)	-4- (5-methylpyrimidinyl)	-CF	-H
				BBH (a, b and c)	-4- (5-methylpyrimidinyl)	-OCH	-H
BBI (a, b and c)	-4- (5-methylpyrimidinyl)	-OCHCH	-H
				BBJ (a, b and c)	-4- (5-methylpyrimidinyl)	-OCF	-H
BBK (a, b and c)	-4- (5-methylpyrimidinyl)	-tert-butyl	-H

BBL (a, b and c)	-4- (5-methylpyrimidinyl)	-isopropyl group	-H
				BBM (a, b and c)	-4- (5-methylpyrimidinyl)	-CH	-CH
BBN (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-H
				BBO (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-Cl
BBP (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-Br
				BBQ (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-F
BBR (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-CH
				BBS (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-CF
BBT (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCH
				BBU (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCHCH
BBV (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCF
				BBW (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-tert-butyl
BBX (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-isopropyl group
				BBY (a, b and c)	-2-pyrazinyl radical	-Cl	-H
BBZ (a, b and c)	-2-pyrazinyl radical	-Br	-H
				BCA (a, b and c)	-2-pyrazinyl radical	-F	-H
BCB (a, b and c)	-2-pyrazinyl radical	-CH	-H
				BCC (a, b and c)	-2-pyrazinyl radical	-CF	-H
BCD (a, b and c)	-2-pyrazinyl radical	-OCH	-H
				BCE (a, b and c)	-2-pyrazinyl radical	-OCHCH	-H
BCF (a, b and c)	-2-pyrazinyl radical	-OCF	-H
				BCG (a, b and c)	-2-pyrazinyl radical	-tert-butyl	-H
BCH (a, b and c)	-2-pyrazinyl radical	-isopropyl group	-H
				BCI (a, b and c)	-2-pyrazinyl radical	-CH	-CH
BCJ (a, b and c)	-2-pyrazinyl radical	-H	-H
				BCK (a, b and c)	-2-pyrazinyl radical	-H	-Cl
BCL (a, b and c)	-2-pyrazinyl radical	-H	-Br

BCM (a, b and c)	-2-pyrazinyl radical	-H	-F
				BCN (a, b and c)	-2-pyrazinyl radical	-H	-CH
BCO (a, b and c)	-2-pyrazinyl radical	-H	-CF
				BCP (a, b and c)	-2-pyrazinyl radical	-H	-OCH
BCQ (a, b and c)	-2-pyrazinyl radical	-H	-OCHCH
				BCR (a, b and c)	-2-pyrazinyl radical	-H	-OCF
BCS (a, b and c)	-2-pyrazinyl radical	-H	-tert-butyl
				BCT (a, b and c)	-2-pyrazinyl radical	-H	-isopropyl group
BCU (a, b and c)	-2- (3-chloropyrazinyl)	-Cl	-H
				BCV (a, b and c)	-2- (3-chloropyrazinyl)	-Br	-H
BCW (a, b and c)	-2- (3-chloropyrazinyl)	-F	-H
				BCX (a, b and c)	-2- (3-chloropyrazinyl)	-CH	-H
BCY (a, b and c)	-2- (3-chloropyrazinyl)	-CF	-H
				BCZ (a, b and c)	-2- (3-chloropyrazinyl)	-OCH	-H
BDA (a, b and c)	-2- (3-chloropyrazinyl)	-OCHCH	-H
				BDB (a, b and c)	-2- (3-chloropyrazinyl)	-OCF	-H
BDC (a, b and c)	-2- (3-chloropyrazinyl)	-tert-butyl	-H
				BDD (a, b and c)	-2- (3-chloropyrazinyl)	-isopropyl group	-H
BDE (a, b and c)	-2- (3-chloropyrazinyl)	-CH	-CH
				BDF (a, b and c)	-2- (3-chloropyrazinyl)	-H	-H
BDG (a, b and c)	-2- (3-chloropyrazinyl)	-H	-Cl
				BDH (a, b and c)	-2- (3-chloropyrazinyl)	-H	-Br
BDI (a, b and c)	-2- (3-chloropyrazinyl)	-H	-F
				BDJ (a, b and c)	-2- (3-chloropyrazinyl)	-H	-CH
BDK (a, b and c)	-2- (3-chloropyrazinyl)	-H	-CF
				BDL (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCH
BDM (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCHCH

BDN (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCF
				BDO (a, b and c)	-2- (3-chloropyrazinyl)	-H	-tert-butyl
BDP (a, b and c)	-2- (3-chloropyrazinyl)	-H	-isopropyl group
				BDQ (a, b and c)	-2- (3-methylpyrazinyl)	-Cl	-H
BDR (a, b and c)	-2- (3-methylpyrazinyl)	-Br	-H
				BDS (a, b and c)	-2- (3-methylpyrazinyl)	-F	-H
BDT (a, b and c)	-2- (3-methylpyrazinyl)	-CH	-H
				BDU (a, b and c)	-2- (3-methylpyrazinyl)	-CF	-H
BDV (a, b and c)	-2- (3-methylpyrazinyl)	-OCH	-H
				BDW (a, b and c)	-2- (3-methylpyrazinyl)	-OCHCH	-H
BDX (a, b and c)	-2- (3-methylpyrazinyl)	-OCF	-H
				BDY (a, b and c)	-2- (3-methylpyrazinyl)	-tert-butyl	-H
BDZ (a, b and c)	-2- (3-methylpyrazinyl)	-isopropyl group	-H
				BEA (a, b and c)	-2- (3-methylpyrazinyl)	-CH	-CH
BEB (a, b and c)	-2- (3-methylpyrazinyl)	-H	-H
				BEC (a, b and c)	-2- (3-methylpyrazinyl)	-H	-Cl
BED (a, b and c)	-2- (3-methylpyrazinyl)	-H	-Br
				BEE (a, b and c)	-2- (3-methylpyrazinyl)	-H	-F
BEF (a, b and c)	-2- (3-methylpyrazinyl)	-H	-CH
				BEG (a, b and c)	-2- (3-methylpyrazinyl)	-H	-CF
BEH (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCH
				BEI (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCHCH
BEJ (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCF
				BEK (a, b and c)	-2- (3-methylpyrazinyl)	-H	-tert-butyl
BEL (a, b and c)	-2- (3-methylpyrazinyl)	-H	-isopropyl group
				BEM (a, b and c)	-2-pyridazinyl radical	-Cl	-H
BEN (a, b and c)	-2-pyridazinyl radical	-Br	-H

BEO (a, b and c)	-2-pyridazinyl radical	-F	-H
				BEP (a, b and c)	-2-pyridazinyl radical	-CH	-H
BEQ (a, b and c)	-2-pyridazinyl radical	-CF	-H
				BER (a, b and c)	-2-pyridazinyl radical	-OCH	-H
BES (a, b and c)	-2-pyridazinyl radical	-OCHCH	-H
				BET (a, b and c)	-2-pyridazinyl radical	-OCF	-H
BEU (a, b and c)	-2-pyridazinyl radical	-tert-butyl	-H
				BEV (a, b and c)	-2-pyridazinyl radical	-isopropyl group	-H
BEW (a, b and c)	-2-pyridazinyl radical	-CH	-CH
				BEX (a, b and c)	-2-pyridazinyl radical	-H	-H
BEY (a, b and c)	-2-pyridazinyl radical	-H	-Cl
				BEZ (a, b and c)	-2-pyridazinyl radical	-H	-Br
BFA (a, b and c)	-2-pyridazinyl radical	-H	-F
				BFB (a, b and c)	-2-pyridazinyl radical	-H	-CH
BFC (a, b and c)	-2-pyridazinyl radical	-H	-CF
				BFD (a, b and c)	-2-pyridazinyl radical	-H	-OCH
BFE (a, b and c)	-2-pyridazinyl radical	-H	-OCHCH
				BFF (a, b and c)	-2-pyridazinyl radical	-H	-OCF
BFG (a, b and c)	-2-pyridazinyl radical	-H	-tert-butyl
				BFH (a, b and c)	-2-pyridazinyl radical	-H	-isopropyl group
BFI (a, b and c)	-3- (4-chloropyridazinyl)	-Cl	-H
				BFJ (a, b and c)	-3- (4-chloropyridazinyl)	-Br	-H
BFK (a, b and c)	-3- (4-chloropyridazinyl)	-F	-H
				BFL (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-H
BFM (a, b and c)	-3- (4-chloropyridazinyl)	-CF	-H
				BFN (a, b and c)	-3- (4-chloropyridazinyl)	-OCH	-H
BFO (a, b and c)	-3- (4-chloropyridazinyl)	-OCHCH	-H

BFP (a, b and c)	-3- (4-chloropyridazinyl)	-OCF	-H
				BFQ (a, b and c)	-3- (4-chloropyridazinyl)	-tert-butyl	-H
BFR (a, b and c)	-3- (4-chloropyridazinyl)	-isopropyl group	-H
				BFS (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-CH
BFT (a, b and c)	-3- (4-chloropyridazinyl)	-H	-H
				BFU (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Cl
BFV (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Br
				BFW (a, b and c)	-3- (4-chloropyridazinyl)	-H	-F
BFX (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CH
				BFY (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CF
BFZ (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCH
				BGA (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCHCH
BGB (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCF
				BGC (a, b and c)	-3- (4-chloropyridazinyl)	-H	-tert-butyl
BGD (a, b and c)	-3- (4-chloropyridazinyl)	-H	-isopropyl group
				BGE (a, b and c)	-3- (4-methylpyridazinyl)	-Cl	-H
BGF (a, b and c)	-3- (4-methylpyridazinyl)	-Br	-H
				BGG (a, b and c)	-3- (4-methylpyridazinyl)	-F	-H
BGH (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-H
				BGI (a, b and c)	-3- (4-methylpyridazinyl)	-CF	-H
BGJ (a, b and c)	-3- (4-methylpyridazinyl)	-OCH	-H
				BGK (a, b and c)	-3- (4-methylpyridazinyl)	-OCHCH	-H
BGL (a, b and c)	-3- (4-methylpyridazinyl)	-OCF	-H
				BGM (a, b and c)	-3- (4-methylpyridazinyl)	-tert-butyl	-H
BGN (a, b and c)	-3- (4-methylpyridazinyl)	-isopropyl group	-H
				BGO (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-CH
BGP (a, b, and c)	-3- (4-methylpyridazinyl)	-H	-H

BGQ (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Cl
				BGR (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Br
BGS (a, b and c)	-3- (4-methylpyridazinyl)	-H	-F
				BGT (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CH
BGU (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CF
				BGV (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCH
BGW (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCHCH
				BGX (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCF
BGY (a, b and c)	-3- (4-methylpyridazinyl)	-H	-tert-butyl
				BGZ (a, b and c)	-3- (4-methylpyridazinyl)	-H	-isopropyl group
BHA (a, b and c)	-4-thiazanyl	-Cl	-H
				BHB (a, b and c)	-4-thiazanyl	-Br	-H
BHC (a, b and c)	-4-thiazanyl	-F	-H
				BHD (a, b and c)	-4-thiazanyl	-CH	-H
BHE (a, b and c)	-4-thiazanyl	-CF	-H
				BHF (a, b and c)	-4-thiazanyl	-OCH	-H
BHG (a, b and c)	-4-thiazanyl	-OCHCH	-H
				BHH (a, b and c)	-4-thiazanyl	-OCF	-H
BHI (a, b and c)	-4-thiazanyl	-tert-butyl	-H
				BHJ (a, b and c)	-4-thiazanyl	-isopropyl group	-H
BHK (a, b and c)	-4-thiazanyl	-CH	-CH
				BHL (a, b and c)	-4-thiazanyl	-H	-H
BHM (a, b and c)	-4-thiazanyl	-H	-Cl
				BHN (a, b and c)	-4-thiazanyl	-H	-Br
BHO (a, b and c)	-4-thiazanyl	-H	-F
				BHP (a, b and c)	-4-thiazanyl	-H	-CH
BHQ (a, b and c)	-4-thiazanyl	-H	-CF

BHR (a, b and c)	-4-thiazanyl	-H	-OCH
				BHS (a, b and c)	-4-thiazanyl	-H	-OCHCH
BHT (a, b and c)	-4-thiazanyl	-H	-OCF
				BHU (a, b and c)	-4-thiazanyl	-H	-tert-butyl
BHV (a, b and c)	-4-thiazanyl	-H	-isopropyl group
				BHW (a, b and c)	-5- (4-chloro-thiazanyl)	-Cl	-H
BHX (a, b and c)	-5- (4-chloro-thiazanyl)	-Br	-H
				BHY (a, b and c)	-5- (4-chloro-thiazanyl)	-F	-H
BHZ (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-H
				BIA (a, b and c)	-5- (4-chloro-thiazanyl)	-CF	-H
BIB (a, b and c)	-5- (4-chloro-thiazanyl)	-OCH	-H
				BIC (a, b and c)	-5- (4-chloro-thiazanyl)	-OCHCH	-H
BID (a, b and c)	-5- (4-chloro-thiazanyl)	-OCF	-H
				BIE (a, b and c)	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
BIF (a, b and c)	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
				BIG (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-CH
BIH (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-H
				BII (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Cl
BIJ (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Br
				BIK (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-F
BIL (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CH
				BIM (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CF
BIN (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCH
				BIO (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCHCH
BIP (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCF
				BIQ (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
BIR (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-isopropyl group

BIS (a, b and c)	-5- (4-methylthiozanyl)	-Cl	-H
				BIT (a, b and c)	-5- (4-methylthiozanyl)	-Br	-H
BIU (a, b and c)	-5- (4-methylthiozanyl)	-F	-H
				BIV (a, b and c)	-5- (4-methylthiozanyl)	-CH	-H
BIW (a, b and c)	-5- (4-methylthiozanyl)	-CF	-H
				BIX (a, b and c)	-5- (4-methylthiozanyl)	-OCH	-H
BIY (a, b and c)	-5- (4-methylthiozanyl)	-OCHCH	-H
				BIZ (a, b and c)	-5- (4-methylthiozanyl)	-OCF	-H
BJA (a, b and c)	-5- (4-methylthiozanyl)	-tert-butyl	-H
				BJB (a, b and c)	-5- (4-methylthiozanyl)	-isopropyl group	-H
BJC (a, b and c)	-5- (4-methylthiozanyl)	-CH	-CH
				BJD (a, b and c)	-5- (4-methylthiozanyl)	-H	-H
BJE (a, b and c)	-5- (4-methylthiozanyl)	-H	-Cl
				BJF (a, b and c)	-5- (4-methylthiozanyl)	-H	-Br
BJG (a, b and c)	-5- (4-methylthiozanyl)	-H	-F
				BJH (a, b and c)	-5- (4-methylthiozanyl)	-H	-CH
BJI (a, b and c)	-5- (4-methylthiozanyl)	-H	-CF
				BJJ (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCH
BJK (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCHCH
				BJL (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCF
BJM (a, b and c)	-5- (4-methylthiozanyl)	-H	-tert-butyl
				BJN (a, b and c)	-5- (4-methylthiozanyl)	-H	-isopropyl group

"a" indicates that the benzoxazole piperazine compound is racemic.

"b" indicates that the carbon atom of the piperazine attached to the methyl group is in the R configuration.

"c" indicates that the carbon atom of the piperazine attached to the methyl group is in the S configuration.

TABLE IV

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				BJO (a, b and c)	-2- (3-chloropyridyl)	-Cl	-H
BJP (a, b and c)	-2- (3-chloropyridyl)	-Br	-H
				BJQ (a, b and c)	-2- (3-chloropyridyl)	-F	-H
BJR (a, b and c)	-2- (3-chloropyridyl)	-CH	-H
				BJS (a, b and c)	-2- (3-chloropyridyl)	-CF	-H
BJT (a, b and c)	-2- (3-chloropyridyl)	-OCH	-H
				BJU (a, b and c)	-2- (3-chloropyridyl)	-OCHCH	-H
BJV (a, b and c)	-2- (3-chloropyridyl)	-OCF	-H
				BJW (a, b and c)	-2- (3-chloropyridyl)	-tert-butyl	-H
BJX (a, b and c)	-2- (3-chloropyridyl)	-isopropyl group	-H
				BJY (a, b and c)	-2- (3-chloropyridyl)	-CH	-CH
BJZ (a, b and c)	-2- (3-chloropyridyl)	-H	-H
				BKA (a, b, and c)	-2- (3-chloropyridyl)	-H	-Cl
BKB (a, b and c)	-2- (3-chloropyridyl)	-H	-Br
				BKC (a, b and c)	-2- (3-chloropyridyl)	-H	-F
BKD (a, b, and c)	-2- (3-chloropyridyl)	-H	-CH
				BKE (a, b, and c)	-2- (3-chloropyridyl)	-H	-CF

BKF (a, b, and c)	-2- (3-chloropyridyl)	-H	-OCH
				BKG (a, b and c)	-2- (3-chloropyridyl)	-H	-OCHCH
BKH (a, b and c)	-2- (3-chloropyridyl)	-H	-OCF
				BKI (a, b and c)	-2- (3-chloropyridyl)	-H	-tert-butyl
BKJ (a, b, and c)	-2- (3-chloropyridyl)	-H	-isopropyl group
				BKK (a, b and c)	-2- (3-methylpyridinyl)	-Cl	-H
BKL (a, b and c)	-2- (3-methylpyridinyl)	-Br	-H
				BKM (a, b, and c)	-2- (3-methylpyridinyl)	-F	-H
BKN (a, b and c)	-2- (3-methylpyridinyl)	-CH	-H
				BKO (a, b, and c)	-2- (3-methylpyridinyl)	-CF	-H
BKP (a, b and c)	-2- (3-methylpyridinyl)	-OCH	-H
				BKQ (a, b and c)	-2- (3-methylpyridinyl)	-OCHCH	-H
BKR (a, b and c)	-2- (3-methylpyridinyl)	-OCF	-H
				BKS (a, b and c)	-2- (3-methylpyridinyl)	-tert-butyl	-H
BKT (a, b and c)	-2- (3-methylpyridinyl)	-isopropyl group	-H
				BKU (a, b, and c)	-2- (3-methylpyridinyl)	-CH	-CH
BKV (a, b and c)	-2- (3-methylpyridinyl)	-H	-H
				BKW (a, b and c)	-2- (3-methylpyridinyl)	-H	-Cl
BKX (a, b and c)	-2- (3-methylpyridinyl)	-H	-Br
				BKY (a, b and c)	-2- (3-methylpyridinyl)	-H	-F
BKZ (a, b and c)	-2- (3-methylpyridinyl)	-H	-CH
				BLA (a, b and c)	-2- (3-methylpyridinyl)	-H	-CF
BLB (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCH
				BLC (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCHCH
BLD (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCF
				BLE (a, b and c)	-2- (3-methylpyridinyl)	-H	-tert-butyl
BLF (a, b and c)	-2- (3-methylpyridinyl)	-H	-isopropyl group

BLG (a, b and c)	-2-(3-CF-pyridyl group)	-Cl	-H
				BLH (a, b and c)	-2-(3-CF-pyridyl group)	-Br	-H
BLI (a, b and c)	-2-(3-CF-pyridyl group)	-F	-H
				BLJ (a, b and c)	-2-(3-CF-pyridyl group)	-CH	-H
BLK (a, b and c)	-2-(3-CF-pyridyl group)	-CF	-H
				BLL (a, b and c)	-2-(3-CF-pyridyl group)	-OCH	-H
BLM (a, b and c)	-2-(3-CF-pyridyl group)	-OCHCH	-H
				BLN (a, b and c)	-2-(3-CF-pyridyl group)	-OCF	-H
BLO (a, b and c)	-2-(3-CF-pyridyl group)	-tert-butyl	-H
				BLP (a, b and c)	-2-(3-CF-pyridyl group)	-isopropyl group	-H
BLQ (a, b and c)	-2-(3-CF-pyridyl group)	-CH	-CH
				BLR (a, b and c)	-2-(3-CF-pyridyl group)	-H	-H
BLS (a, b and c)	-2-(3-CF-pyridyl group)	-H	-Cl
				BLT (a, b and c)	-2-(3-CF-pyridyl group)	-H	-Br
BLU (a, b and c)	-2-(3-CF-pyridyl group)	-H	-F
				BLV (a, b and c)	-2-(3-CF-pyridinePyridyl radical)	-H	-CH
BLW (a, b and c)	-2-(3-CF-pyridyl group)	-H	-CF
				BLX (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCH
BLY (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCHCH
				BLZ (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCF
BMA (a, b and c)	-2-(3-CF-pyridyl group)	-H	-tert-butyl
				BMB (a, b and c)	-2-(3-CF-pyridyl group)	-H	-isopropyl group
BMC (a, b and c)	-4- (5-chloropyrimidinyl)	-Cl	-H
				BMD (a, b and c)	-4- (5-chloropyrimidinyl)	-Br	-H
BME (a, b and c)	-4- (5-chloropyrimidinyl)	-F	-H
				BMF (a, b and c)	-4- (5-chloropyrimidinyl)	-CH	-H
BMG (a, b and c)	-4- (5-chloropyrimidinyl)	-CF	-H

BMH (a, b and c)	-4- (5-chloropyrimidinyl)	-OCH	-H
				BMI (a, b and c)	-4- (5-chloropyrimidinyl)	-OCHCH	-H
BMJ (a, b and c)	-4- (5-chloropyrimidinyl)	-OCF	-H
				BMK (a, b and c)	-4- (5-chloropyrimidinyl)	-tert-butyl	-H
BML (a, b and c)	-4- (5-chloropyrimidinyl)	-isopropyl group	-H
				BMM (a, b and c)	-4- (5-chloropyrimidinyl)	-CH	-CH
BMN (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-H
				BMO (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-Cl
BMP (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-Br
				BMQ (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-F
BMR (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-CH
				BMS (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-CF
BMT (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCH
				BMU (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCHCH
BMV (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCF
				BMW (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-tert-butyl
BMX (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-isopropyl group
				BMY (a, b and c)	-4- (5-methylpyrimidinyl)	-Cl	-H
BMZ (a, b and c)	-4- (5-methylpyrimidinyl)	-Br	-H
				BNA (a, b, and c)	-4- (5-methylpyrimidinyl)	-F	-H
BNB (a, b, and c)	-4- (5-methylpyrimidinyl)	-CH	-H
				BNC (a, b and c)	-4- (5-methylpyrimidinyl)	-CF	-H
BND (a, b and c)	-4- (5-methylpyrimidinyl)	-OCH	-H
				BNE (a, b, and c)	-4- (5-methylpyrimidinyl)	-OCHCH	-H
BNF (a, b and c)	-4- (5-methylpyrimidinyl)	-OCF	-H
				BNG (a, b and c)	-4- (5-methylpyrimidinyl)	-tert-butyl	-H
BNH (a, b and c)	-4- (5-methylpyrimidinyl)	-isopropyl group	-H

BNI (a, b, and c)	-4- (5-methylpyrimidinyl)	-CH	-CH
				BNJ (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-H
BNK (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-Cl
				BNL (a, b, and c)	-4- (5-methylpyrimidinyl)	-H	-Br
BNM (a, b, and c)	-4- (5-methylpyrimidinyl)	-H	-F
				BNN (a, b, and c)	-4- (5-methylpyrimidinyl)	-H	-CH
BNO (a, b, and c)	-4- (5-methylpyrimidinyl)	-H	-CF
				BNP (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCH
BNQ (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCHCH
				BNR (a, b, and c)	-4- (5-methylpyrimidinyl)	-H	-OCF
BNS (a, b, and c)	-4- (5-methylpyrimidinyl)	-H	-tert-butyl
				BNT (a, b, and c)	-4- (5-methylpyrimidinyl)	-H	-isopropyl group
BNU (a, b and c)	-2-pyrazinyl radical	-Cl	-H
				BNV (a, b, and c)	-2-pyrazinyl radical	-Br	-H
BNW (a, b, and c)	-2-pyrazinyl radical	-F	-H
				BNX (a, b and c)	-2-pyrazinyl radical	-CH	-H
BNY (a, b and c)	-2-pyrazinyl radical	-CF	-H
				BNZ (a, b, and c)	-2-pyrazinyl radical	-OCH	-H
BOA (a, b and c)	-2-pyrazinyl radical	-OCHCH	-H
				BOB (a, b and c)	-2-pyrazinyl radical	-OCF	-H
BOC (a, b and c)	-2-pyrazinyl radical	-tert-butyl	-H
				BOD (a, b and c))	-2-pyrazinyl radical	-isopropyl group	-H
BOE (a, b and c)	-2-pyrazinyl radical	-CH	-CH
				BOF (a, b and c)	-2-pyrazinyl radical	-H	-H
BOG (a, b and c)	-2-pyrazinyl radical	-H	-Cl
				BOH (a, b and c)	-2-pyrazinyl radical	-H	-Br
BOI (a, b and c)	-2-pyrazinyl radical	-H	-F

BOJ (a, b and c)	-2-pyrazinyl radical	-H	-CH
				BOK (a, b and c)	-2-pyrazinyl radical	-H	-CF
BOL (a, b and c)	-2-pyrazinyl radical	-H	-OCH
				BOM (a, b and c)	-2-pyrazinyl radical	-H	-OCHCH
BON (a, b and c)	-2-pyrazinyl radical	-H	-OCF
				BOO (a, b and c)	-2-pyrazinyl radical	-H	-tert-butyl
BOP (a, b and c)	-2-pyrazinyl radical	-H	-isopropyl group
				BOQ (a, b and c)	-2- (3-chloropyrazinyl)	-Cl	-H
BOR (a, b and c)	-2- (3-chloropyrazinyl)	-Br	-H
				BOS (a, b and c)	-2- (3-chloropyrazinyl)	-F	-H
BOT (a, b and c)	-2- (3-chloropyrazinyl)	-CH	-H
				BOU (a, b and c)	-2- (3-chloropyrazinyl)	-CF	-H
BOV (a, b and c)	-2- (3-chloropyrazinyl)	-OCH	-H
				BOW (a, b and c)	-2- (3-chloropyrazinyl)	-OCHCH	-H
BOX (a, b and c)	-2- (3-chloropyrazinyl)	-OCF	-H
				BOY (a, b and c)	-2- (3-chloropyrazinyl)	-tert-butyl	-H
BOZ (a, b and c)	-2- (3-chloropyrazinyl)	-isopropyl group	-H
				BPA (a, b and c)	-2- (3-chloropyrazinyl)	-CH	-CH
BPB (a, b and c)	-2- (3-chloropyrazinyl)	-H	-H
				BPC (a, b and c)	-2- (3-chloropyrazinyl)	-H	-Cl
BPD (a, b and c)	-2- (3-chloropyrazinyl)	-H	-Br
				BPE (a, b and c)	-2- (3-chloropyrazinyl)	-H	-F
BPF (a, b and c)	-2- (3-chloropyrazinyl)	-H	-CH
				BPG (a, b and c)	-2- (3-chloropyrazinyl)	-H	-CF
BPH (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCH
				BPI (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCHCH
BPJ (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCF

BPK (a, b and c)	-2- (3-chloropyrazinyl)	-H	-tert-butyl
				BPL (a, b and c)	-2- (3-chloropyrazinyl)	-H	-isopropyl group
BPM (a, b and c)	-2- (3-methylpyrazinyl)	-Cl	-H
				BPN (a, b and c)	-2- (3-methylpyrazinyl)	-Br	-H
BPO (a, b and c)	-2- (3-methylpyrazinyl)	-F	-H
				BPP (a, b and c)	-2- (3-methylpyrazinyl)	-CH	-H
BPQ (a, b and c)	-2- (3-methylpyrazinyl)	-CF	-H
				BPR (a, b and c)	-2- (3-methylpyrazinyl)	-OCH	-H
BPS (a, b and c)	-2- (3-methylpyrazinyl)	-OCHCH	-H
				BPT (a, b and c)	-2- (3-methylpyrazinyl)	-OCF	-H
BPU (a, b and c)	-2- (3-methylpyrazinyl)	-tert-butyl	-H
				BPV (a, b and c)	-2- (3-methylpyrazinyl)	-isopropyl group	-H
BPW (a, b and c)	-2- (3-methylpyrazinyl)	-CH	-CH
				BPX (a, b and c)	-2- (3-methylpyrazinyl)	-H	-H
BPY (a, b and c)	-2- (3-methylpyrazinyl)	-H	-Cl
				BPZ (a, b and c)	-2- (3-methylpyrazinyl)	-H	-Br
BQA (a, b and c)	-2- (3-methylpyrazinyl)	-H	-F
				BQB (a, b and c)	-2- (3-methylpyrazinyl)	-H	-CH
BQC (a, b and c)	-2- (3-methylpyrazinyl)	-H	-CF
				BQD (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCH
BQE (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCHCH
				BQF (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCF
BQG (a, b and c)	-2- (3-methylpyrazinyl)	-H	-tert-butyl
				BQH (a, b and c)	-2- (3-methylpyrazinyl)	-H	-isopropyl group
BQI (a, b and c)	-2-pyridazinyl radical	-Cl	-H
				BQJ (a, b and c)	-2-pyridazinyl radical	-Br	-H
BQK (a, b and c)	-2-pyridazinyl radical	-F	-H

BQL (a, b and c)	-2-pyridazinyl radical	-CH	-H
				BQM (a, b and c)	-2-pyridazinyl radical	-CF	-H
BQN (a, b and c)	-2-pyridazinyl radical	-OCH	-H
				BQO (a, b and c)	-2-pyridazinyl radical	-OCHCH	-H
BQP (a, b and c)	-2-pyridazinyl radical	-OCF	-H
				BQQ (a, b and c)	-2-pyridazinyl radical	-tert-butyl	-H
BQR (a, b and c)	-2-pyridazinyl radical	-isopropyl group	-H
				BQS (a, b and c)	-2-pyridazinyl radical	-CH	-CH
BQT (a, b and c)	-2-pyridazinyl radical	-H	-H
				BQU (a, b and c)	-2-pyridazinyl radical	-H	-Cl
BQV (a, b and c)	-2-pyridazinyl radical	-H	-Br
				BQW (a, b and c)	-2-pyridazinyl radical	-H	-F
BQX (a, b and c)	-2-pyridazinyl radical	-H	-CH
				BQY (a, b and c)	-2-pyridazinyl radical	-H	-CF
BQZ (a, b and c)	-2-pyridazinyl radical	-H	-OCH
				BRA (a, b and c)	-2-pyridazinyl radical	-H	-OCHCH
BRB (a, b and c)	-2-pyridazinyl radical	-H	-OCF
				BRC (a, b and c)	-2-pyridazinyl radical	-H	-tert-butyl
BRD (a, b and c)	-2-pyridazinyl radical	-H	-isopropyl group
				BRE (a, b and c)	-3- (4-chloropyridazinyl)	-Cl	-H
BRF (a, b and c)	-3- (4-chloropyridazinyl)	-Br	-H
				BRG (a, b and c)	-3- (4-chloropyridazinyl)	-F	-H
BRH (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-H
				BRI (a, b and c)	-3- (4-chloropyridazinyl)	-CF	-H
BRJ (a, b and c)	-3- (4-chloropyridazinyl)	-OCH	-H
				BRK (a, b and c)	-3- (4-chloropyridazinyl)	-OCHCH	-H
BRL (a, b and c)	-3- (4-chloropyridazinyl)	-OCF	-H

BRM (a, b and c)	-3- (4-chloropyridazinyl)	-tert-butyl	-H
				BRN (a, b and c)	-3- (4-chloropyridazinyl)	-isopropyl group	-H
BRO (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-CH
				BRP (a, b and c)	-3- (4-chloropyridazinyl)	-H	-H
BRQ (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Cl
				BRR (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Br
BRS (a, b and c)	-3- (4-chloropyridazinyl)	-H	-F
				BRT (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CH
BRU (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CF
				BRV (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCH
BRW (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCHCH
				BRX (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCF
BRY (a, b and c)	-3- (4-chloropyridazinyl)	-H	-tert-butyl
				BRZ (a, b and c)	-3- (4-chloropyridazinyl)	-H	-isopropyl group
BSA (a, b and c)	-3- (4-methylpyridazinyl)	-Cl	-H
				BSB (a, b and c)	-3-(4-methyl pyridazinyl group)	-Br	-H
BSC (a, b and c)	-3- (4-methylpyridazinyl)	-F	-H
				BSD (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-H
BSE (a, b and c)	-3- (4-methylpyridazinyl)	-CF	-H
				BSF (a, b and c)	-3- (4-methylpyridazinyl)	-OCH	-H
BSG (a, b and c)	-3- (4-methylpyridazinyl)	-OCHCH	-H
				BSH (a, b and c)	-3- (4-methylpyridazinyl)	-OCF	-H
BSI (a, b and c)	-3- (4-methylpyridazinyl)	-tert-butyl	-H
				BSJ (a, b and c)	-3- (4-methylpyridazinyl)	-isopropyl group	-H
BSK (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-CH
				BSL (a, b and c)	-3- (4-methylpyridazinyl)	-H	-H
BSM (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Cl

BSN (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Br
				BSO (a, b and c)	-3- (4-methylpyridazinyl)	-H	-F
BSP (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CH
				BSQ (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CF
BSR (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCH
				BSS (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCHCH
BST (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCF
				BSU (a, b and c)	-3- (4-methylpyridazinyl)	-H	-tert-butyl
BSV (a, b and c)	-3- (4-methylpyridazinyl)	-H	-isopropyl group
				BSW (a, b and c)	-4-thiazanyl	-Cl	-H
BSX (a, b and c)	-4-thiazanyl	-Br	-H
				BSY (a, b and c)	-4-thiazanyl	-F	-H
BSZ (a, b and c)	-4-thiazanyl	-CH	-H
				BTA (a, b and c)	-4-thiazanyl	-CF	-H
BTB (a, b and c)	-4-thiazanyl	-OCH	-H
				BTC (a, b and c)	-4-thiazanyl	-OCHCH	-H
BTD (a, b and c)	-4-thiazanyl	-OCF	-H
				BTE (a, b and c)	-4-thiazanyl	-tert-butyl	-H
BTF (a, b and c)	-4-thiazanyl	-isopropyl group	-H
				BTG (a, b and c)	-4-thiazanyl	-CH	-CH
BTH (a, b and c)	-4-thiazanyl	-H	-H
				BTI (a, b and c)	-4-thiazanyl	-H	-Cl
BTJ (a, b and c)	-4-tbiazanyl	-H	-Br
				BTK (a, b and c)	-4-thiazanyl	-H	-F
BTL (a, b and c)	-4-thiazanyl	-H	-CH
				BTMs (a, b and c)	-4-thiazanyl	-H	-CF
BTN (a, b and c)	-4-thiazanyl	-H	-OCH

BTO (a, b and c)	-4-thiazanyl	-H	-OCHCH
				BTP (a, b and c)	-4-thiazanyl	-H	-OCF
BTQ (a, b and c)	-4-thiazanyl	-H	-tert-butyl
				BTR (a, b and c)	-4-thiazanyl	-H	-isopropyl group
BTS (a, b and c)	-5- (4-chloro-thiazanyl)	-Cl	-H
				BTT (a, b and c)	-5- (4-chloro-thiazanyl)	-Br	-H
BTU (a, b and c)	-5- (4-chloro-thiazanyl)	-F	-H
				BTV (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-H
BTW (a, b and c)	-5- (4-chloro-thiazanyl)	-CF	-H
				BTX (a, b and c)	-5- (4-chloro-thiazanyl)	-OCH	-H
BTY (a, b and c)	-5- (4-chloro-thiazanyl)	-OCHCH	-H
				BTZ (a, b and c)	-5- (4-chloro-thiazanyl)	-OCF	-H
BUA (a, b and c)	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
				BUB (a, b and c)	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
BUC (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-CH
				BUD (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-H
BUE (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Cl
				BUF (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Br
BUG (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-F
				BUH (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CH
BUI (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CF
				BUJ (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCH
BUK (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCHCH
				BUL (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCF
BUM (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
				BUN (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-isopropyl group
BUO (a, b and c)	-5- (4-methylthiozanyl)	-Cl	-H

BUP (a, b and c)	-5- (4-methylthiozanyl)	-Br	-H
				BUQ (a, b and c)	-5- (4-methylthiozanyl)	-F	-H
BUR (a, b and c)	-5- (4-methylthiozanyl)	-CH	-H
				BUS (a, b and c)	-5- (4-methylthiozanyl)	-CF	-H
BUT (a, b and c)	-5- (4-methylthiozanyl)	-OCH	-H
				BUU (a, b and c)	-5- (4-methylthiozanyl)	-OCHCH	-H
BUV (a, b and c)	-5- (4-methylthiozanyl)	-OCF	-H
				BUW (a, b and c)	-5- (4-methylthiozanyl)	-tert-butyl	-H
BUX (a, b and c)	-5- (4-methylthiozanyl)	-isopropyl group	-H
				BUY (a, b and c)	-5- (4-methylthiozanyl)	-CH	-CH
BUZ (a, b and c)	-5- (4-methylthiozanyl)	-H	-H
				BVA (a, b and c)	-5- (4-methylthiozanyl)	-H	-Cl
BVB (a, b and c)	-5- (4-methyl)thiazanyl)	-H	-Br
				BVC (a, b and c)	-5- (4-methylthiozanyl)	-H	-F
BVD (a, b and c)	-5- (4-methylthiozanyl)	-H	-CH
				BVE (a, b and c)	-5- (4-methylthiozanyl)	-H	-CF
BVF (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCH
				BVG (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCHCH
BVH (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCF
				BVI (a, b and c)	-5- (4-methylthiozanyl)	-H	-tert-butyl
BVJ (a, b and c)	-5- (4-methylthiozanyl)	-H	-isopropyl group

"a" indicates that the benzoxazole piperazine compound is racemic.

"b" indicates that the carbon atom of the piperazine attached to the methyl group is in the R configuration.

"c" indicates that the carbon atom of the piperazine attached to the methyl group is in the S configuration.

TABLE V

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				BVK	-2-pyridazinyl radical	-Cl	-H
BVL	-2-pyridazinyl radical	-Br	-H
				BVM	-2-pyridazinyl radical	-F	-H
BVN	-2-pyridazinyl radical	-CH	-H
				BVO	-2-pyridazinyl radical	-CF	-H
BVP	-2-pyridazinyl radical	-OCH	-H
				BVQ	-2-pyridazinyl radical	-OCHCH	-H
BVR	-2-pyridazinyl radical	-OCF	-H
				BVS	-2-pyridazinyl radical	-tert-butyl	-H
BVT	-2-pyridazinyl radical	-isopropyl group	-H
				BVU	-2-pyridazinyl radical	-CH	-CH
BVV	-2-pyridazinyl radical	-H	-H
				BVW	-2-pyridazinyl radical	-H	-Cl
BVX	-2-pyridazinyl radical	-H	-Br
				BVY	-2-pyridazinyl radical	-H	-F

BVZ	-2-pyridazinyl radical	-H	-CH
				BWA	-2-pyridazinyl radical	-H	-CF
BWB	-2-pyridazinyl radical	-H	-OCH
				BWC	-2-pyridazinyl radical	-H	-OCHCH
BWD	-2-pyridazinyl radical	-H	-OCF
				BWE	-2-pyridazinyl radical	-H	-tert-butyl
BWF	-2-pyridazinyl radical	-H	-isopropyl group
				BWG	-3- (4-chloropyridazinyl)	-Cl	-H
BWH	-3- (4-chloropyridazinyl)	-Br	-H
				BWI	-3- (4-chloropyridazinyl)	-F	-H
BWJ	-3- (4-chloropyridazinyl)	-CH	-H
				BWK	-3- (4-chloropyridazinyl)	-CF	-H
BWL	-3- (4-chloropyridazinyl)	-OCH	-H
				BWM	-3- (4-chloropyridazinyl)	-OCHCH	-H
BWN	-3- (4-chloropyridazinyl)	-OCF	-H
				BWO	-3- (4-chloropyridazinyl)	-tert-butyl	-H
BWP	-3- (4-chloropyridazinyl)	-isopropyl group	-H
				BWQ	-3- (4-chloropyridazinyl)	-CH	-CH
BWR	-3- (4-chloropyridazinyl)	-H	-H
				BWS	-3- (4-chloropyridazinyl)	-H	-Cl
BWT	-3- (4-chloropyridazinyl)	-H	-Br
				BWU	-3- (4-chloropyridazinyl)	-H	-F
BWV	-3- (4-chloropyridazinyl)	-H	-CH
				BWW	-3- (4-chloropyridazinyl)	-H	-CF
BWX	-3- (4-chloropyridazinyl)	-H	-OCH
				BWY	-3- (4-chloropyridazinyl)	-H	-OCHCH
BWZ	-3- (4-chloropyridazinyl)	-H	-OCF

BXA	-3- (4-chloropyridazinyl)	-H	-tert-butyl
				BXB	-3- (4-chloropyridazinyl)	-H	-isopropyl group
BXC	-3- (4-methylpyridazinyl)	-Cl	-H
				BXD	-3- (4-methylpyridazinyl)	-Br	-H
BXE	-3- (4-methylpyridazinyl)	-F	-H
				BXF	-3- (4-methylpyridazinyl)	-CH	-H
BXG	-3- (4-methylpyridazinyl)	-CF	-H
				BXH	-3- (4-methylpyridazinyl)	-OCH	-H
BXI	-3- (4-methylpyridazinyl)	-OCHCH	-H
				BXJ	-3- (4-methylpyridazinyl)	-OCF	-H
BXK	-3- (4-methylpyridazinyl)	-tert-butyl	-H
				BXL	-3- (4-methylpyridazinyl)	-isopropyl group	-H
BXM	-3- (4-methylpyridazinyl)	-CH	-CH
				BXN	-3- (4-methylpyridazinyl)	-H	-H
BXO	-3- (4-methylpyridazinyl)	-H	-Cl
				BXP	-3- (4-methylpyridazinyl)	-H	-Br
BXQ	-3- (4-methylpyridazinyl)	-H	-F
				BXR	-3- (4-methylpyridazinyl)	-H	-CH
BXS	-3- (4-methylpyridazinyl)	-H	-CF
				BXT	-3- (4-methylpyridazinyl)	-H	-OCH
BXU	-3- (4-methylpyridazinyl)	-H	-OCHCH
				BXV	-3- (4-methylpyridazinyl)	-H	-OCF
BXW	-3- (4-methylpyridazinyl)	-H	-tert-butyl
				BXX	-3- (4-methylpyridazinyl)	-H	-isopropyl group
BXY	-4-thiazanyl	-Cl	-H
				BXZ	-4-thiazanyl	-Br	-H
BYA	-4-thiazanyl	-F	-H
				BYB	-4-thiazanyl	-CH	-H

BYC	-4-thiazanyl	-CF	-H
				BYD	-4-thiazanyl	-OCH	-H
BYE	-4-thiazanyl	-OCHCH	-H
				BYF	-4-thiazanyl	-OCF	-H
BYG	-4-thiazanyl	-tert-butyl	-H
				BYH	-4-thiazanyl	-isopropyl group	-H
BYI	-4-thiazanyl	-CH	-CH
				BYJ	-4-thiazanyl	-H	-H
BYK	-4-thiazanyl	-H	-Cl
				BYL	-4-thiazanyl	-H	-Br
BYM	-4-thiazanyl	-H	-F
				BYN	-4-thiazanyl	-H	-CH
BYO	-4-thiazanyl	-H	-CF
				BYP	-4-thiazanyl	-H	-OCH
BYQ	-4-thiazanyl	-H	-OCHCH
				BYR	-4-thiazanyl	-H	-OCF
BYS	-4-thiazanyl	-H	-tert-butyl
				BYT	-4-thiazanyl	-H	-isopropyl group
BYU	-5- (4-chloro-thiazanyl)	-Cl	-H
				BYV	-5- (4-chloro-thiazanyl)	-Br	-H
BYW	-5- (4-chloro-thiazanyl)	-F	-H
				BYX	-5- (4-chloro-thiazanyl)	-CH	-H
BYY	-5- (4-chloro-thiazanyl)	-CF	-H
				BYZ	-5- (4-chloro-thiazanyl)	-OCH	-H
BZA	-5- (4-chloro-thiazanyl)	-OCHCH	-H
				BZB	-5- (4-chloro-thiazanyl)	-OCF	-H
BZC	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
				BZD	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
BZE	-5- (4-chloro-thiazanyl)	-CH	-CH

BZF	-5- (4-chloro-thiazanyl)	-H	-H
				BZG	-5- (4-chloro-thiazanyl)	-H	-Cl
BZH	-5- (4-chloro-thiazanyl)	-H	-Br
				BZI	-5- (4-chloro-thiazanyl)	-H	-F
BZJ	-5- (4-chloro-thiazanyl)	-H	-CH
				BZK	-5- (4-chloro-thiazanyl)	-H	-CF
BZL	-5- (4-chloro-thiazanyl)	-H	-OCH
				BZM	-5- (4-chloro-thiazanyl)	-H	-OCHCH
BZN	-5- (4-chloro-thiazanyl)	-H	-OCF
				BZO	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
BZP	-5- (4-chloro-thiazanyl)	-H	-isopropyl group
				BZQ	-5- (4-methylthiozanyl)	-Cl	-H
BZR	-5- (4-methylthiozanyl)	-Br	-H
				BZS	-5- (4-methylthiozanyl)	-F	-H
BZT	-5- (4-methylthiozanyl)	-CH	-H
				BZU	-5- (4-methylthiozanyl)	-CF	-H
BZV	-5- (4-methylthiozanyl)	-OCH	-H
				BZW	-5- (4-methylthiozanyl)	-OCHCH	-H
BZX	-5- (4-methylthiozanyl)	-OCF	-H
				BZY	-5- (4-methylthiozanyl)	-tert-butyl	-H
BZZ	-5- (4-methylthiozanyl)	-isopropyl group	-H
				CAA	-5- (4-methylthiozanyl)	-CH	-CH
CAB	-5- (4-methylthiozanyl)	-H	-H
				CAC	-5- (4-methylthiozanyl)	-H	-Cl
CAD	-5- (4-methylthiozanyl)	-H	-Br
				CAE	-5- (4-methylthiozanyl)	-H	-F
CAF	-5- (4-methylthiozanyl)	-H	-CH

CAG	-5- (4-methylthiozanyl)	-H	-CF
				CAH	-5- (4-methylthiozanyl)	-H	-OCH
CAI	-5- (4-methylthiozanyl)	-H	-OCHCH
				CAJ	-5- (4-methylthiozanyl)	-H	-OCF
CAK	-5- (4-methylthiozanyl)	-H	-tert-butyl
				CAL	-5- (4-methylthiozanyl)	-H	-isopropyl group

TABLE VI

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				CAM	-2- (3-chloropyridyl)	-Cl	-H
CAN	-2- (3-chloropyridyl)	-Br	-H
				CAO	-2- (3-chloropyridyl)	-F	-H
CAP	-2- (3-chloropyridyl)	-CH	-H
				CAQ	-2- (3-chloropyridyl)	-CF	-H
CAR	-2- (3-chloropyridyl)	-OCH	-H
				CAS	-2- (3-chloropyridyl)	-OCHCH	-H
CAT	-2- (3-chloropyridyl)	-OCF	-H
				CAU	-2- (3-chloropyridyl)	-tert-butyl	-H
CAV	-2- (3-chloropyridyl)	-isopropyl group	-H

CAW	-2- (3-chloropyridyl)	-CH	-CH
				CAX	-2- (3-chloropyridyl)	-H	-H
CAY	-2- (3-chloropyridyl)	-H	-Cl
				CAZ	-2- (3-chloropyridyl)	-H	-Br
CBA	-2- (3-chloropyridyl)	-H	-F
				CBB	-2- (3-chloropyridyl)	-H	-CH
CBC	-2- (3-chloropyridyl)	-H	-CF
				CBD	-2- (3-chloropyridyl)	-H	-OCH
CBE	-2- (3-chloropyridyl)	-H	-OCHCH
				CBF	-2- (3-chloropyridyl)	-H	-OCF
CBG	-2- (3-chloropyridyl)	-H	-tert-butyl
				CBH	-2- (3-chloropyridyl)	-H	-isopropyl group
CBI	-2- (3-methylpyridinyl)	-Cl	-H
				CBJ	-2- (3-methylpyridinyl)	-Br	-H
CBK	-2- (3-methylpyridinyl)	-F	-H
				CBL	-2- (3-methylpyridinyl)	-CH	-H
CBM	-2- (3-methylpyridinyl)	-CF	-H
				CBN	-2- (3-methylpyridinyl)	-OCH	-H
CBO	-2- (3-methylpyridinyl)	-OCHCH	-H
				CBP	-2- (3-methylpyridinyl)	-OCF	-H
CBQ	-2- (3-methylpyridinyl)	-tert-butyl	-H
				CBR	-2- (3-methylpyridinyl)	-isopropyl group	-H
CBS	-2- (3-methylpyridinyl)	-CH	-CH
				CBT	-2- (3-methylpyridinyl)	-H	-H
CBU	-2- (3-methylpyridinyl)	-H	-Cl
				CBV	-2- (3-methylpyridinyl)	-H	-Br
CBW	-2- (3-methylpyridinyl)	-H	-F

CBX	-2- (3-methylpyridinyl)	-H	-CH
				CBY	-2- (3-methylpyridinyl)	-H	-CF
CBZ	-2- (3-methylpyridinyl)	-H	-OCH
				CCA	-2- (3-methylpyridinyl)	-H	-OCHCH
CCB	-2- (3-methylpyridinyl)	-H	-OCF
				CCC	-2- (3-methylpyridinyl)	-H	-tert-butyl
CCD	-2- (3-methylpyridinyl)	-H	-isopropyl group
				CCE	-2-(3-CF-pyridyl group)	-Cl	-H
CCF	-2-(3-CF-pyridyl group)	-Br	-H
				CCG	-2-(3-CF-pyridyl group)	-F	-H
CCH	-2-(3-CF-pyridyl group)	-CH	-H
				CCI	-2-(3-CF-pyridyl group)	-CF	-H
CCJ	-2-(3-CF-pyridyl group)	-OCH	-H
				CCK	-2-(3-CF-pyridyl group)	-OCHCH	-H
CCL	-2-(3-CF-pyridyl group)	-OCF	-H
				CCM	-2-(3-CF-pyridyl group)	-tert-butyl	-H
CCN	-2-(3-CF-pyridyl group)	-isopropyl group	-H
				CCO	-2-(3-CF-pyridyl group)	-CH	-CH
CCP	-2-(3-CF-pyridyl group)	-H	-H
				CCQ	-2-(3-CF-pyridyl group)	-H	-Cl
CCR	-2-(3-CF-pyridyl group)	-H	-Br
				CCS	-2-(3-CF-pyridyl group)	-H	-F
CCT	-2-(3-CF-pyridyl group)	-H	-CH
				CCU	-2-(3-CF-pyridyl group)	-H	-CF
CCV	-2-(3-CF-pyridyl group)	-H	-OCH
				CCW	-2-(3-CF-pyridyl group)	-H	-OCHCH
CCX	-2-(3-CF-pyridyl group)	-H	-OCF

CCY	-2-(3-CF-pyridyl group)	-H	-tert-butyl
				CCZ	-2-(3-CF-pyridyl group)	-H	-isopropyl group
CDA	-4- (5-chloropyrimidinyl)	-Cl	-H
				CDB	-4- (5-chloropyrimidinyl)	-Br	-H
CDC	-4- (5-chloropyrimidinyl)	-F	-H
				CDD	-4- (5-chloropyrimidinyl)	-CH	-H
CDE	-4- (5-chloropyrimidinyl)	-CF	-H
				CDF	-4- (5-chloropyrimidinyl)	-OCH	-H
CDG	-4- (5-chloropyrimidinyl)	-OCHCH	-H
				CDH	-4- (5-chloropyrimidinyl)	-OCF	-H
CDI	-4- (5-chloropyrimidinyl)	-tert-butyl	-H
				CDJ	-4- (5-chloropyrimidinyl)	-isopropyl group	-H
CDK	-4- (5-chloropyrimidinyl)	-CH	-CH
				CDL	-4- (5-chloropyrimidinyl)	-H	-H
CDM	-4- (5-chloropyrimidinyl)	-H	-Cl
				CDN	-4- (5-chloropyrimidinyl)	-H	-Br
CDO	-4- (5-chloropyrimidinyl)	-H	-F
				CDP	-4- (5-chloropyrimidinyl)	-H	-CH
CDQ	-4- (5-chloropyrimidinyl)	-H	-CF
				CDR	-4- (5-chloropyrimidinyl)	-H	-OCH
CDS	-4- (5-chloropyrimidinyl)	-H	-OCHCH
				CDT	-4- (5-chloropyrimidinyl)	-H	-OCF
CDU	-4- (5-chloropyrimidinyl)	-H	-tert-butyl
				CDV	-4- (5-chloropyrimidinyl)	-H	-isopropyl group
CDW	-4- (5-methylpyrimidinyl)	-Cl	-H
				CDX	-4- (5-methylpyrimidinyl)	-Br	-H
CDY	-4- (5-methylpyrimidinyl)	-F	-H

CDZ	-4- (5-methylpyrimidinyl)	-CH	-H
				CEA	-4- (5-methylpyrimidinyl)	-CF	-H
CEB	-4- (5-methylpyrimidinyl)	-OCH	-H
				CEC	-4- (5-methylpyrimidinyl)	-OCHCH	-H
CED	-4- (5-methylpyrimidinyl)	-OCF	-H
				CEE	-4- (5-methylpyrimidinyl)	-tert-butyl	-H
CEF	-4- (5-methylpyrimidinyl)	-isopropyl group	-H
				CEG	-4- (5-methylpyrimidinyl)	-CH	-CH
CEH	-4- (5-methylpyrimidinyl)	-H	-H
				CEI	-4- (5-methylpyrimidinyl)	-H	-Cl
CEJ	-4- (5-methylpyrimidinyl)	-H	-Br
				CEK	-4- (5-methylpyrimidinyl)	-H	-F
CEL	-4- (5-methylpyrimidinyl)	-H	-CH
				CEM	-4- (5-methylpyrimidinyl)	-H	-CF
CEN	-4- (5-methylpyrimidinyl)	-H	-OCH
				CEO	-4- (5-methylpyrimidinyl)	-H	-OCHCH
CEP	-4- (5-methylpyrimidinyl)	-H	-OCF
				CEQ	-4- (5-methylpyrimidinyl)	-H	-tert-butyl
CER	-4- (5-methylpyrimidinyl)	-H	-isopropyl group
				CES	-2-pyrazinyl radical	-Cl	-H
CET	-2-pyrazinyl radical	-Br	-H
				CEU	-2-pyrazinyl radical	-F	-H
CEV	-2-pyrazinyl radical	-CH	-H
				CEW	-2-pyrazinyl radical	-CF	-H
CEX	-2-pyrazinyl radical	-OCH	-H
				CEY	-2-pyrazinyl radical	-OCHCH	-H
CEZ	-2-pyrazinyl radical	-OCF	-H

CFA	-2-pyrazinyl radical	-tert-butyl	-H
				CFB	-2-pyrazinyl radical	-isopropyl group	-H
CFC	-2-pyrazinyl radical	-CH	-CH
				CFD	-2-pyrazinyl radical	-H	-H
CFE	-2-pyrazinyl radical	-H	-Cl
				CFF	-2-pyrazinyl radical	-H	-Br
CFG	-2-pyrazinyl radical	-H	-F
				CFH	-2-pyrazinyl radical	-H	-CH
CFI	-2-pyrazinyl radical	-H	-CF
				CFJ	-2-pyrazinyl radical	-H	-OCH
CFK	-2-pyrazinyl radical	-H	-OCHCH
				CFL	-2-pyrazinyl radical	-H	-OCF
CFM	-2-pyrazinyl radical	-H	-tert-butyl
				CFN	-2-pyrazinyl radical	-H	-isopropyl group
CFO	-2- (3-chloropyrazinyl)	-Cl	-H
				CFP	-2- (3-chloropyrazinyl)	-Br	-H
CFQ	-2- (3-chloropyrazinyl)	-F	-H
				CFR	-2- (3-chloropyrazinyl)	-CH	-H
CFS	-2- (3-chloropyrazinyl)	-CF	-H
				CFT	-2- (3-chloropyrazinyl)	-OCH	-H
CFU	-2- (3-chloropyrazinyl)	-OCHCH	-H
				CFV	-2- (3-chloropyrazinyl)	-OCF	-H
CFW	-2- (3-chloropyrazinyl)	-tert-butyl	-H
				CFX	-2- (3-chloropyrazinyl)	-isopropyl group	-H
CFY	-2- (3-chloropyrazinyl)	-CH	-CH
				CFZ	-2- (3-chloropyrazinyl)	-H	-H
CGA	-2- (3-chloropyrazinyl)	-H	-Cl

CGB	-2- (3-chloropyrazinyl)	-H	-Br
				CGC	-2- (3-chloropyrazinyl)	-H	-F
CGD	-2- (3-chloropyrazinyl)	-H	-CH
				CGE	-2- (3-chloropyrazinyl)	-H	-CF
CGF	-2- (3-chloropyrazinyl)	-H	-OCH
				CGG	-2- (3-chloropyrazinyl)	-H	-OCHCH
CGH	-2- (3-chloropyrazinyl)	-H	-OCF
				CGI	-2- (3-chloropyrazinyl)	-H	-tert-butyl
CGJ	-2- (3-chloropyrazinyl)	-H	-isopropyl group
				CGK	-2- (3-methylpyrazinyl)	-Cl	-H
CGL	-2- (3-methylpyrazinyl)	-Br	-H
				CGM	-2- (3-methylpyrazinyl)	-F	-H
CGN	-2- (3-methylpyrazinyl)	-CH	-H
				CGO	-2- (3-methylpyrazinyl)	-CF	-H
CGP	-2- (3-methylpyrazinyl)	-OCH	-H
				CGQ	-2- (3-methylpyrazinyl)	-OCHCH	-H
CGR	-2- (3-methylpyrazinyl)	-OCF	-H
				CGS	-2- (3-methylpyrazinyl)	-tert-butyl	-H
CGT	-2- (3-methylpyrazinyl)	-isopropyl group	-H
				CGU	-2- (3-methylpyrazinyl)	-CH	-CH
CGV	-2- (3-methylpyrazinyl)	-H	-H
				CGW	-2- (3-methylpyrazinyl)	-H	-Cl
CGX	-2- (3-methylpyrazinyl)	-H	-Br
				CGY	-2- (3-methylpyrazinyl)	-H	-F
CGZ	-2- (3-methylpyrazinyl)	-H	-CH
				CHA	-2- (3-methylpyrazinyl)	-H	-CF
CHB	-2- (3-methylpyrazinyl)	-H	-OCH

CHC	-2- (3-methylpyrazinyl)	-H	-OCHCH
				CHD	-2- (3-methylpyrazinyl)	-H	-OCF
CHE	-2- (3-methylpyrazinyl)	-H	-tert-butyl
				CHF	-2- (3-methylpyrazinyl)	-H	-isopropyl group
CHG	-2-pyridazinyl radical	-Cl	-H
				CHH	-2-pyridazinyl radical	-Br	-H
CHI	-2-pyridazinyl radical	-F	-H
				CHJ	-2-pyridazinyl radical	-CH	-H
CHK	-2-pyridazinyl radical	-CF	-H
				CHL	-2-pyridazinyl radical	-OCH	-H
CHM	-2-pyridazinyl radical	-OCHCH	-H
				CHN	-2-pyridazinyl radical	-OCF	-H
CHO	-2-pyridazinyl radical	-tert-butyl	-H
				CHP	-2-pyridazinyl radical	-isopropyl group	-H
CHQ	-2-pyridazinyl radical	-CH	-CH
				CHR	-2-pyridazinyl radical	-H	-H
CHS	-2-pyridazinyl radical	-H	-Cl
				CHT	-2-pyridazinyl radical	-H	-Br
CHU	-2-pyridazinyl radical	-H	-F
				CHV	-2-pyridazinyl radical	-H	-CH
CHW	-2-pyridazinyl radical	-H	-CF
				CHX	-2-pyridazinyl radical	-H	-OCH
CHY	-2-pyridazinyl radical	-H	-OCHCH
				CHZ	-2-pyridazinyl radical	-H	-OCF
CIA	-2-pyridazinyl radical	-H	-tert-butyl
				CIB	-2-pyridazinyl radical	-H	-isopropyl group
CIC	-3- (4-chloropyridazinyl)	-Cl	-H

CID	-3- (4-chloropyridazinyl)	-Br	-H
				CIE	-3- (4-chloropyridazinyl)	-F	-H
CIF	-3- (4-chloropyridazinyl)	-CH	-H
				CIG	-3- (4-chloropyridazinyl)	-CF	-H
CIH	-3- (4-chloropyridazinyl)	-OCH	-H
				CII	-3- (4-chloropyridazinyl)	-OCHCH	-H
CIJ	-3- (4-chloropyridazinyl)	-OCF	-H
				CIK	-3- (4-chloropyridazinyl)	-tert-butyl	-H
CIL	-3- (4-chloropyridazinyl)	-isopropyl group	-H
				CIM	-3- (4-chloropyridazinyl)	-CH	-CH
CIN	-3- (4-chloropyridazinyl)	-H	-H
				CIO	-3- (4-chloropyridazinyl)	-H	-Cl
CIP	-3- (4-chloropyridazinyl)	-H	-Br
				CIQ	-3- (4-chloropyridazinyl)	-H	-F
CIR	-3- (4-chloropyridazinyl)	-H	-CH
				CIS	-3- (4-chloropyridazinyl)	-H	-CF
CIT	-3- (4-chloropyridazinyl)	-H	-OCH
				CIU	-3- (4-chloropyridazinyl)	-H	-OCHCH
CIV	-3- (4-chloropyridazinyl)	-H	-OCF
				CIW	-3- (4-chloropyridazinyl)	-H	-tert-butyl
CIX	-3- (4-chloropyridazinyl)	-H	-isopropyl group
				CIY	-3- (4-methylpyridazinyl)	-Cl	-H
CIZ	-3- (4-methylpyridazinyl)	-Br	-H
				CJA	-3- (4-methylpyridazinyl)	-F	-H
CJB	-3- (4-methylpyridazinyl)	-CH	-H
				CJC	-3- (4-methylpyridazinyl)	-CF	-H
CJD	-3- (4-methylpyridazinyl)	-OCH	-H

CJE	-3- (4-methylpyridazinyl)	-OCHCH	-H
				CJF	-3- (4-methylpyridazinyl)	-OCF	-H
CJG	-3- (4-methylpyridazinyl)	-tert-butyl	-H
				CJH	-3- (4-methylpyridazinyl)	-isopropyl group	-H
CJI	-3- (4-methylpyridazinyl)	-CH	-CH
				CJJ	-3- (4-methylpyridazinyl)	-H	-H
CJK	-3- (4-methylpyridazinyl)	-H	-Cl
				CJL	-3- (4-methylpyridazinyl)	-H	-Br
CJM	-3- (4-methylpyridazinyl)	-H	-F
				CJN	-3- (4-methylpyridazinyl)	-H	-CH
CJO	-3- (4-methylpyridazinyl)	-H	-CF
				CJP	-3- (4-methylpyridazinyl)	-H	-OCH
CJQ	-3- (4-methylpyridazinyl)	-H	-OCHCH
				CJR	-3- (4-methylpyridazinyl)	-H	-OCF
CJS	-3- (4-methylpyridazinyl)	-H	-tert-butyl
				CJT	-3- (4-methylpyridazinyl)	-H	-isopropyl group
CJU	-4-thiazanyl	-Cl	-H
				CJV	-4-thiazanyl	-Br	-H
CJW	-4-thiazanyl	-F	-H
				CJX	-4-thiazanyl	-CH	-H
CJY	-4-thiazanyl	-CF	-H
				CJZ	-4-thiazanyl	-OCH	-H
CKA	-4-thiazanyl	-OCHCH	-H
				CKB	-4-thiazanyl	-OCF	-H
CKC	-4-thiazanyl	-tert-butyl	-H
				CKD	-4-thiazanyl	-isopropyl group	-H
CKE	-4-thiazanyl	-CH	-CH
				CKF	-4-thiazanyl	-H	-H
CKG	-4-thiazanyl	-H	-Cl

CKH	-4-thiazanyl	-H	-Br
				CKI	-4-thiazanyl	-H	-F
CKJ	-4-thiazanyl	-H	-CH
				CKK	-4-thiazanyl	-H	-CF
CKL	-4-thiazanyl	-H	-OCH
				CKM	-4-thiazanyl	-H	-OCHCH
CKN	-4-thiazanyl	-H	-OCF
				CKO	-4-thiazanyl	-H	-tert-butyl
CKP	-4-thiazanyl	-H	-isopropyl group
				CKQ	-5- (4-chloro-thiazanyl)	-Cl	-H
CKR	-5- (4-chloro)Substituted thiazanyl)	-Br	-H
				CKS	-5- (4-chloro-thiazanyl)	-F	-H
CKT	-5- (4-chloro-thiazanyl)	-CH	-H
				CKU	-5- (4-chloro-thiazanyl)	-CF	-H
CKV	-5- (4-chloro-thiazanyl)	-OCH	-H
				CKW	-5- (4-chloro-thiazanyl)	-OCHCH	-H
CKX	-5- (4-chloro-thiazanyl)	-OCF	-H
				CKY	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
CKZ	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
				CLA	-5- (4-chloro-thiazanyl)	-CH	-CH
CLB	-5- (4-chloro-thiazanyl)	-H	-H
				CLC	-5- (4-chloro-thiazanyl)	-H	-Cl
CLD	-5- (4-chloro-thiazanyl)	-H	-Br
				CLE	-5- (4-chloro-thiazanyl)	-H	-F
CLF	-5- (4-chloro-thiazanyl)	-H	-CH
				CLG	-5- (4-chloro-thiazanyl)	-H	-CF
CLH	-5- (4-chloro-thiazanyl)	-H	-OCH
				CLI	-5- (4-chloro-thiazanyl)	-H	-OCHCH

CLJ	-5- (4-chloro-t)hiazanyl)	-H	-OCF
				CLK	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
CLL	-5- (4-chloro-thiazanyl)	-H	-isopropyl group
				CLM	-5- (4-methylthiozanyl)	-Cl	-H
CLN	-5- (4-methylthiozanyl)	-Br	-H
				CLO	-5- (4-methylthiozanyl)	-F	-H
CLP	-5- (4-methylthiozanyl)	-CH	-H
				CLQ	-5- (4-methylthiozanyl)	-CF	-H
CLR	-5- (4-methylthiozanyl)	-OCH	-H
				CLS	-5- (4-methylthiozanyl)	-OCHCH	-H
CLT	-5- (4-methylthiozanyl)	-OCF	-H
				CLU	-5- (4-methylthiozanyl)	-tert-butyl	-H
CLV	-5- (4-methylthiozanyl)	-isopropyl group	-H
				CLW	-5- (4-methylthiozanyl)	-CH	-CH
CLX	-5- (4-methylthiozanyl)	-H	-H
				CLY	-5- (4-methylthiozanyl)	-H	-Cl
CLZ	-5- (4-methylthiozanyl)	-H	-Br
				CMA	-5- (4-methylthiozanyl)	-H	-F
CMB	-5- (4-methylthiozanyl)	-H	-CH
				CMC	-5- (4-methylthiozanyl)	-H	-CF
CMD	-5- (4-methylthiozanyl)	-H	-OCH
				CME	-5- (4-methylthiozanyl)	-H	-OCHCH
CMF	-5- (4-methylthiozanyl)	-H	-OCF
				CMG	-5- (4-methylthiozanyl)	-H	-tert-butyl
CMH	-5- (4-methylthiozanyl)	-H	-isopropyl group

TABLE VII

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				CMI (a, b and c)	-2-pyridazinyl radical	-Cl	-H
CMJ (a, b and c)	-2-pyridazinyl radical	-Br	-H
				CMK (a, b and c)	-2-pyridazinyl radical	-F	-H
CML (a, b and c)	-2-pyridazinyl radical	-CH	-H
				CMM (a, b and c)	-2-pyridazinyl radical	-CF	-H
CMN (a, b and c)	-2-pyridazinyl radical	-OCH	-H
				CMO (a, b and c)	-2-pyridazinyl radical	-OCHCH	-H
CMP (a, b and c)	-2-pyridazinyl radical	-OCF	-H
				CMQ (a, b and c)	-2-pyridazinyl radical	-tert-butyl	-H
CMR (a, b and c)	-2-pyridazinyl radical	-isopropyl group	-H
				CMS (a, b and c)	-2-pyridazinyl radical	-CH	-CH
CMT (a, b and c)	-2-pyridazinyl radical	-H	-H
				CMU (a, b and c)	-2-pyridazinyl radical	-H	-Cl
CMV (a, b and c)	-2-pyridazinyl radical	-H	-Br
				CMW (a, b and c)	-2-pyridazinyl radical	-H	-F
CMX (a, b and c)	-2-pyridazinyl radical	-H	-CH
				CMY (a, b and c)	-2-pyridazinyl radical	-H	-CF

CMZ (a, b and c)	-2-pyridazinyl radical	-H	-OCH
				CNA (a, b and c)	-2-pyridazinyl radical	-H	-OCHCH
CNB (a, b and c)	-2-pyridazinyl radical	-H	-OCF
				CNC (a, b and c)	-2-pyridazinyl radical	-H	-tert-butyl
CND (a, b and c)	-2-pyridazinyl radical	-H	-isopropyl group
				CNE (a, b and c)	-3- (4-chloropyridazinyl)	-Cl	-H
CNF (a, b and c)	-3- (4-chloropyridazinyl)	-Br	-H
				CNG (a, b and c)	-3- (4-chloropyridazinyl)	-F	-H
CNH (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-H
				CNI (a, b and c)	-3- (4-chloropyridazinyl)	-CF	-H
CNJ (a, b and c)	-3- (4-chloropyridazinyl)	-OCH	-H
				CNK (a, b and c)	-3- (4-chloropyridazinyl)	-OCHCH	-H
CNL (a, b and c)	-3- (4-chloropyridazinyl)	-OCF	-H
				CNM (a, b and c)	-3- (4-chloropyridazinyl)	-tert-butyl	-H
CNN (a, b and c)	-3- (4-chloropyridazinyl)	-isopropyl group	-H
				CNO (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-CH
CNP (a, b and c)	-3- (4-chloropyridazinyl)	-H	-H
				CNQ (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Cl
CNR (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Br
				CNS (a, b and c)	-3- (4-chloropyridazinyl)	-H	-F
CNT (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CH
				CNU (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CF
CNV (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCH
				CNW (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCHCH
CNX (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCF
				CNY (a, b and c)	-3- (4-chloropyridazinyl)	-H	-tert-butyl
CNZ (a, b and c)	-3- (4-chloropyridazinyl)	-H	-isopropyl group

COA (a, b and c)	-3- (4-methylpyridazinyl)	-Cl	-H
				COB (a, b and c)	-3- (4-methylpyridazinyl)	-Br	-H
COC (a, b and c)	-3- (4-methylpyridazinyl)	-F	-H
				COD (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-H
COE (a, b and c)	-3- (4-methylpyridazinyl)	-CF	-H
				COF (a, b and c)	-3- (4-methylpyridazinyl)	-OCH	-H
COG (a, b and c)	-3- (4-methylpyridazinyl)	-OCHCH	-H
				COH (a, b and c)	-3- (4-methylpyridazinyl)	-OCF	-H
COI (a, b and c)	-3- (4-methylpyridazinyl)	-tert-butyl	-H
				COJ (a, b and c)	-3- (4-methylpyridazinyl)	-isopropyl group	-H
COK (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-CH
				COL (a, b and c)	-3- (4-methylpyridazinyl)	-H	-H
COM (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Cl
				CON (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Br
COO (a, b and c)	-3- (4-methylpyridazinyl)	-H	-F
				COP (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CH
COQ (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CF
				COR (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCH
COS (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCHCH
				COT (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCF
COU (a, b and c)	-3- (4-methylpyridazinyl)	-H	-tert-butyl
				COV (a, b and c)	-3- (4-methylpyridazinyl)	-H	-isopropyl group
COW (a, b and c)	-4-thiazanyl	-Cl	-H
				COX (a, b and c)	-4-thiazanyl	-Br	-H
COY (a, b and c)	-4-thiazanyl	-F	-H
				COZ (a, b and c)	-4-thiazanyl	-CH	-H
CPA (a, b and c)	-4-thiazanyl	-CF	-H

CPB (a, b and c)	-4-thiazanyl	-OCH	-H
				CPC (a, b and c)	-4-thiazanyl	-OCHCH	-H
CPD (a, b and c)	-4-thiazanyl	-OCF	-H
				CPE (a, b and c)	-4-thiazanyl	-tert-butyl	-H
CPF (a, b and c)	-4-thiazanyl	-isopropyl group	-H
				CPG (a, b and c)	-4-thiazanyl	-CH	-CH
CPH (a, b and c)	-4-thiazanyl	-H	-H
				CPI (a, b and c)	-4-thiazanyl	-H	-Cl
CPJ (a, b and c)	-4-thiazanyl	-H	-Br
				CPK (a, b and c)	-4-thiazanyl	-H	-F
CPL (a, b and c)	-4-thiazanyl	-H	-CH
				CPM (a, b and c)	-4-thiazanyl	-H	-CF
CPN (a, b and c)	-4-thiazanyl	-H	-OCH
				CPO (a, b and c)	-4-thiazanyl	-H	-OCHCH
CPP (a, b and c)	-4-thiazanyl	-H	-OCF
				CPQ (a, b and c)	-4-thiazanyl	-H	-tert-butyl
CPR (a, b and c)	-4-thiazanyl	-H	-isopropyl group
				CPS (a, b and c)	-5- (4-chloro-thiazanyl)	-Cl	-H
CPT (a, b and c)	-5- (4-chloro-thiazanyl)	-Br	-H
				CPU (a, b and c)	-5- (4-chloro-thiazanyl)	-F	-H
CPV (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-H
				CPW (a, b and c)	-5- (4-chloro-thiazanyl)	-CF	-H
CPX (a, b and c)	-5- (4-chloro-thiazanyl)	-OCH	-H
				CPY (a, b and c)	-5- (4-chloro-thiazanyl)	-OCHCH	-H
CPZ (a, b and c)	-5- (4-chloro-thiazanyl)	-OCF	-H
				CQA (a, b and c)	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
CQB (a, b and c)	-5- (4-chloro-thiazanyl)	-isopropyl group	-H

CQC (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-CH
				CQD (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-H
CQE (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Cl
				CQF (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Br
CQG (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-F
				CQH (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CH
CQI (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CF
				CQJ (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCH
CQK (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCHCH
				CQL (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCF
CQM (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
				CQN (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-isopropyl group
CQO (a, b and c)	-5- (4-methylthiozanyl)	-Cl	-H
				CQP (a, b and c)	-5- (4-methylthiozanyl)	-Br	-H
CQQ (a, b and c)	-5- (4-methylthiozanyl)	-F	-H
				CQR (a, b and c)	-5- (4-methylthiozanyl)	-CH	-H
CQS (a, b and c)	-5- (4-methylthiozanyl)	-CF	-H
				CQT (a, b and c)	-5- (4-methylthiozanyl)	-OCH	-H
CQU (a, b and c)	-5- (4-methylthiozanyl)	-OCHCH	-H
				CQV (a, b and c)	-5- (4-methylthiozanyl)	-OCF	-H
CQW (a, b and c)	-5- (4-methylthiozanyl)	-tert-butyl	-H
				CQX (a, b and c)	-5- (4-methylthiozanyl)	-isopropyl group	-H
CQY (a, b and c)	-5- (4-methylthiozanyl)	-CH	-CH
				CQZ (a, b and c)	-5- (4-methylthiozanyl)	-H	-H
CRA (a, b and c)	-5- (4-methylthiozanyl)	-H	-Cl
				CRB (a, b and c)	-5- (4-methylthiozanyl)	-H	-Br
CRC (a, b and c)	-5- (4-methylthiozanyl)	-H	-F

CRD (a, b and c)	-5- (4-methylthiozanyl)	-H	-CH
				CRE (a, b and c)	-5- (4-methylthiozanyl)	-H	-CF
CRF (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCH
				CRG (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCHCH
CRH (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCF
				CRI (a, b and c)	-5- (4-methylthiozanyl)	-H	-tert-butyl
CRJ (a, b and c)	-5- (4-methylthiozanyl)	-H	-isopropyl group

"a" indicates that the benzoxazole piperazine compound is racemic.

"b" indicates that the carbon atom of the piperazine attached to the methyl group is in the R configuration.

"c" indicates that the carbon atom of the piperazine attached to the methyl group is in the S configuration.

TABLE VIII

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				CRK (a, b and c)	-2- (3-chloropyridyl)	-Cl	-H
CRL (a, b and c)	-2- (3-chloropyridyl)	-Br	-H
				CRM (a, b, and c)	-2- (3-chloropyridyl)	-F	-H
CRN (a, b and c)	-2- (3-chloropyridyl)	-CH	-H
				CRO (a, b and c)	-2- (3-chloropyridyl)	-CF	-H
CRP (a, b and c)	-2- (3-chloropyridyl)	-OCH	-H
				CRQ (a, b and c)	-2- (3-chloropyridyl)	-OCHCH	-H
CRR (a, b and c)	-2- (3-chloropyridyl)	-OCF	-H
				CRS (a, b and c)	-2- (3-chloropyridyl)	-tert-butyl	-H
CRT (a, b and c)	-2- (3-chloropyridyl)	-isopropyl group	-H
				CRU (a, b and c)	-2- (3-chloropyridyl)	-CH	-CH
CRV (a, b and c)	-2- (3-chloropyridyl)	-H	-H
				CRW (a, b and c)	-2- (3-chloropyridyl)	-H	-Cl
CRX (a, b and c)	-2- (3-chloropyridyl)	-H	-Br
				CRY (a, b and c)	-2- (3-chloropyridyl)	-H	-F
CRZ (a, b and c)	-2- (3-chloropyridyl)	-H	-CH
				CSA (a, b and c)	-2- (3-chloropyridyl)	-H	-CF
CSB (a, b and c)	-2- (3-chloropyridyl)	-H	-OCH
				CSC (a, b and c)	-2- (3-chloropyridyl)	-H	-OCHCH
CSD (a, b and c)	-2- (3-chloropyridyl)	-H	-OCF
				CSE (a, b and c)	-2- (3-chloropyridyl)	-H	-tert-butyl
CSF (a, b and c)	-2- (3-chloropyridyl)	-H	-isopropyl group
				CSG (a, b and c)	-2- (3-methylpyridinyl)	-Cl	-H
CSH (a, b and c)	-2- (3-methylpyridinyl)	-Br	-H
				CSI (a, b and c)	-2- (3-methylpyridinyl)	-F	-H

CSJ (a, b and c)	-2- (3-methylpyridinyl)	-CH	-H
				CSK (a, b and c)	-2- (3-methylpyridinyl)	-CF	-H
CSL (a, b and c)	-2- (3-methylpyridinyl)	-OCH	-H
				CSM (a, b and c)	-2- (3-methylpyridinyl)	-OCHCH	-H
CSN(aB and c)	-2- (3-methylpyridinyl)	-OCF	-H
				CSO (a, b and c)	-2- (3-methylpyridinyl)	-tert-butyl	-H
CSP (a, b and c)	-2- (3-methylpyridinyl)	-isopropyl group	-H
				CSQ (a, b and c)	-2- (3-methylpyridinyl)	-CH	-CH
CSR (a, b and c)	-2- (3-methylpyridinyl)	-H	-H
				CSS (a, b and c)	-2- (3-methylpyridinyl)	-H	-Cl
CST (a, b and c)	-2- (3-methylpyridinyl)	-H	-Br
				CSU (a, b and c)	-2- (3-methylpyridinyl)	-H	-F
CSV (a, b and c)	-2- (3-methylpyridinyl)	-H	-CH
				CSW (a, b and c)	-2- (3-methylpyridinyl)	-H	-CF
CSX (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCH
				CSY (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCHCH
CSZ (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCF
				CTA (a, b and c)	-2- (3-methylpyridinyl)	-H	-tert-butyl
CTB (a, b and c)	-2- (3-methylpyridinyl)	-H	-isopropyl group
				CTC (a, b and c)	-2-(3-CF-pyridyl group)	-Cl	-H
CTD (a, b and c)	-2-(3-CF-pyridyl group)	-Br	-H
				CTE (a, b and c)	-2-(3-CF-pyridyl group)	-F	-H
CTF (a, b and c)	-2-(3-CF-pyridyl group)	-CH	-H
				CTG (a, b and c)	-2-(3-CF-pyridyl group)	-CF	-H
CTH (a, b and c)	-2-(3-CF-pyridyl group)	-OCH	-H
				CTI (a, b and c)	-2-(3-CF-pyridyl group)	-OCHCH	-H
CTJ (a, b and c)	-2-(3-CF-pyridyl group)	-OCF	-H

CTK (a, b and c)	-2-(3-CF-pyridyl group)	-tert-butyl	-H
				CTL (a, b and c)	-2-(3-CF-pyridyl group)	-isopropyl group	-H
CTM (a, b and c)	-2-(3-CF-pyridyl group)	-CH	-CH
				CTN (a, b and c)	-2-(3-CF-pyridyl group)	-H	-H
CTO (a, b and c)	-2-(3-CF-pyridyl group)	-H	-Cl
				CTP (a, b and c)	-2-(3-CF-pyridyl group)	-H	-Br
CTQ (a, b and c)	-2-(3-CF-pyridyl group)	-H	-F
				CTR (a, b and c)	-2-(3-CF-pyridyl group)	-H	-CH
CTS (a, b and c)	-2-(3-CF-pyridyl group)	-H	-CF
				CTT (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCH
CTU (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCHCH
				CTV (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCF
CTW(a，b and c)	-2-(3-CF-pyridyl group)	-H	-tert-butyl
				CTX (a, b and c)	-2-(3-CF-pyridyl group)	-H	-isopropyl group
CTY (a, b and c)	-4- (5-chloropyrimidinyl)	-Cl	-H
				CTZ (a, b and c)	-4- (5-chloropyrimidinyl)	-Br	-H
CUA (a, b and c)	-4- (5-chloropyrimidinyl)	-F	-H
				CUB (a, b and c)	-4- (5-chloropyrimidinyl)	-CH	-H
CUC (a, b and c)	-4- (5-chloropyrimidinyl)	-CF	-H
				CUD (a, b and c)	-4- (5-chloropyrimidinyl)	-OCH	-H
CUE (a, b and c)	-4- (5-chloropyrimidinyl)	-OCHCH	-H
				CUF (a, b and c)	-4- (5-chloropyrimidinyl)	-OCF	-H
CUG (a, b and c)	-4- (5-chloropyrimidinyl)	-tert-butyl	-H
				CUH (a, b and c)	-4- (5-chloropyrimidinyl)	-isopropyl group	-H
CUI (a, b and c)	-4- (5-chloropyrimidinyl)	-CH	-CH
				CUJ (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-H
CUK (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-Cl

CUL (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-Br
				CUM (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-F
CUN (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-CH
				CUO (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-CF
CUP (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCH
				CUQ (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCHCH
CUR (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCF
				CUS (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-tert-butyl
CUT (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-isopropyl group
				CUU (a, b and c)	-4- (5-methylpyrimidinyl)	-Cl	-H
CUV (a, b and c)	-4- (5-methylpyrimidinyl)	-Br	-H
				CUW (a, b and c)	-4- (5-methylpyrimidinyl)	-F	-H
CUX (a, b and c)	-4- (5-methylpyrimidinyl)	-CH	-H
				CUY (a, b and c)	-4- (5-methylpyrimidinyl)	-CF	-H
CUZ (a, b and c)	-4- (5-methylpyrimidinyl)	-OCH	-H
				CVA(a，bAnd c)	-4- (5-methylpyrimidinyl)	-OCHCH	-H
CVB (a, b and c)	-4- (5-methylpyrimidinyl)	-OCF	-H
				CVC (a, b and c)	-4- (5-methylpyrimidinyl)	-tert-butyl	-H
CVD (a, b and c)	-4- (5-methylpyrimidinyl)	-isopropyl group	-H
				CVE (a, b and c)	-4- (5-methylpyrimidinyl)	-CH	-CH
CVF (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-H
				CVG (a, b and c)	-4- (5-methylpyrimidine)Pyridyl radical)	-H	-Cl
CVH (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-Br
				CVI (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-F
CVJ (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-CH
				CVK (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-CF
CVL (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCH

CVM (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCHCH
				CVN (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCF
CVO (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-tert-butyl
				CVP (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-isopropyl group
CVQ (a, b and c)	-2-pyrazinyl radical	-Cl	-H
				CVR (a, b and c)	-2-pyrazinyl radical	-Br	-H
CVS (a, b and c)	-2-pyrazinyl radical	-F	-H
				CVT (a, b and c)	-2-pyrazinyl radical	-CH	-H
CVU (a, b and c)	-2-pyrazinyl radical	-CF	-H
				CVV (a, b and c)	-2-pyrazinyl radical	-OCH	-H
CVW (a, b and c)	-2-pyrazinyl radical	-OCHCH	-H
				CVX (a, b and c)	-2-pyrazinyl radical	-OCF	-H
CVY (a, b and c)	-2-pyrazinyl radical	-tert-butyl	-H
				CVZ (a, b and c)	-2-pyrazinyl radical	-isopropyl group	-H
CWA (a, b and c)	-2-pyrazinyl radical	-CH	-CH
				CWB (a, b and c)	-2-pyrazinyl radical	-H	-H
CWC (a, b and c)	-2-pyrazinyl radical	-H	-Cl
				CWD (a, b and c)	-2-pyrazinyl radical	-H	-Br
CWE (a, b and c)	-2-pyrazinyl radical	-H	-F
				CWF (a, b and c)	-2-pyrazinyl radical	-H	-CH
CWG (a, b and c)	-2-pyrazinyl radical	-H	-CF
				CWH (a, b and c)	-2-pyrazinyl radical	-H	-OCH
CWI (a, b and c)	-2-pyrazinyl radical	-H	-OCHCH
				CWJ (a, b and c)	-2-pyrazinyl radical	-H	-OCF
CWK (a, b and c)	-2-pyrazinyl radical	-H	-tert-butyl
				CWL (a, b and c)	-2-pyrazinyl radical	-H	-isopropyl group
CWM (a, b and c)	-2- (3-chloropyrazinyl)	-Cl	-H

CWN (a, b and c)	-2- (3-chloropyrazinyl)	-Br	-H
				CWO (a, b and c)	-2- (3-chloropyrazinyl)	-F	-H
CWP (a, b and c)	-2- (3-chloropyrazinyl)	-CH	-H
				CWQ (a, b and c)	-2- (3-chloropyrazinyl)	-CF	-H
CWR (a, b and c)	-2- (3-chloropyrazinyl)	-OCH	-H
				CWS (a, b and c)	-2- (3-chloropyrazinyl)	-OCHCH	-H
CWT (a, b and c)	-2- (3-chloropyrazinyl)	-OCF	-H
				CWu (a, b and c)	-2- (3-chloropyrazinyl)	-tert-butyl	-H
CWV (a, b and c)	-2- (3-chloropyrazinyl)	-isopropyl group	-H
				CWW (a, b and c)	-2- (3-chloropyrazinyl)	-CH	-CH
CWX (a, b and c)	-2- (3-chloropyrazinyl)	-H	-H
				CWY (a, b and c)	-2- (3-chloropyrazinyl)	-H	-Cl
CWZ (a, b and c)	-2- (3-chloropyrazinyl)	-H	-Br
				CXA (a, b and c)	-2- (3-chloropyrazinyl)	-H	-F
CXB (a, b and c)	-2- (3-chloropyrazinyl)	-H	-CH
				CXC (a, b and c)	-2- (3-chloropyrazinyl)	-H	-CF
CXD (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCH
				CXE (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCHCH
CXF (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCF
				CXG (a, b and c)	-2- (3-chloropyrazinyl)	-H	-tert-butyl
CXH (a, b and c)	-2- (3-chloropyrazinyl)	-H	-isopropyl group
				CXI (a, b and c)	-2- (3-methylpyrazinyl)	-Cl	-H
CXJ (a, b and c)	-2- (3-methylpyrazinyl)	-Br	-H
				CXK (a, b and c)	-2- (3-methylpyrazinyl)	-F	-H
CXL (a, b and c)	-2- (3-methylpyrazinyl)	-CH	-H
				CXM (a, b and c)	-2- (3-methylpyrazinyl)	-CF	-H
CXN (a, b and c)	-2- (3-methylpyrazinyl)	-OCH	-H

CXO (a, b and c)	-2- (3-methylpyrazinyl)	-OCHCH	-H
				CXP (a, b and c)	-2- (3-methylpyrazinyl)	-OCF	-H
CXQ (a, b and c)	-2- (3-methylpyrazinyl)	-tert-butyl	-H
				CXR (a, b and c)	-2- (3-methylpyrazinyl)	-isopropyl group	-H
CXS (a, b and c)	-2- (3-methylpyrazinyl)	-CH	-CH
				CXT (a, b and c)	-2- (3-methylpyrazinyl)	-H	-H
CXU (a, b and c)	-2- (3-methylpyrazinyl)	-H	-Cl
				CXV (a, b and c)	-2- (3-methylpyrazinyl)	-H	-Br
CXW (a, b and c)	-2- (3-methylpyrazinyl)	-H	-F
				CXX (a, b and c)	-2- (3-methylpyrazinyl)	-H	-CH
CXY (a, b and c)	-2- (3-methylpyrazinyl)	-H	-CF
				CXZ (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCH
CYA (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCHCH
				CYB (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCF
CYC (a, b and c)	-2- (3-methylpyrazinyl)	-H	-tert-butyl
				CYD (a, b and c)	-2- (3-methylpyrazinyl)	-H	-isopropyl group
CYE (a, b and c)	-2-pyridazinyl radical	-Cl	-H
				CYF (a, b and c)	-2-pyridazinyl radical	-Br	-H
CYG (a, b and c)	-2-pyridazinyl radical	-F	-H
				CYH (a, b and c)	-2-pyridazinyl radical	-CH	-H
CYI (a, b and c)	-2-pyridazinyl radical	-CF	-H
				CYJ (a, b and c)	-2-pyridazinyl radical	-OCH	-H
CYK (a, b and c)	-2-pyridazinyl radical	-OCHCH	-H
				CYL (a, b and c)	-2-pyridazinyl radical	-OCF	-H
CYM (a, b and c)	-2-pyridazinyl radical	-tert-butyl	-H
				CYN (a, b and c)	-2-pyridazinyl radical	-isopropyl group	-H
CYO (a, b and c)	-2-pyridazinyl radical	-CH	-CH

CYP (a, b and c)	-2-pyridazinyl radical	-H	-H
				CYQ (a, b and c)	-2-pyridazinyl radical	-H	-Cl
CYR (a, b and c)	-2-pyridazinyl radical	-H	-Br
				CYS (a, b and c)	-2-pyridazinyl radical	-H	-F
CYT (a, b and c)	-2-pyridazinyl radical	-H	-CH
				CYU (a, b and c)	-2-pyridazinyl radical	-H	-CF
CYV (a, b and c)	-2-pyridazinyl radical	-H	-OCH
				CYW (a, b and c)	-2-pyridazinyl radical	-H	-OCHCH
CYX (a, b and c)	-2-pyridazinyl radical	-H	-OCF
				CYY (a, b and c)	-2-DaOxazine radical	-H	-tert-butyl
CYZ (a, b and c)	-2-pyridazinyl radical	-H	-isopropyl group
				CZA (a, b and c)	-3- (4-chloropyridazinyl)	-Cl	-H
CZB (a, b and c)	-3- (4-chloropyridazinyl)	-Br	-H
				CZC (a, b and c)	-3- (4-chloropyridazinyl)	-F	-H
CZD (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-H
				CZE (a, b and c)	-3- (4-chloropyridazinyl)	-CF	-H
CZF (a, b and c)	-3- (4-chloropyridazinyl)	-OCH	-H
				CZG (a, b and c)	-3- (4-chloropyridazinyl)	-OCHCH	-H
CZH (a, b and c)	-3- (4-chloropyridazinyl)	-OCF	-H
				CZI (a, b and c)	-3- (4-chloropyridazinyl)	-tert-butyl	-H
CZJ (a, b and c)	-3- (4-chloropyridazinyl)	-isopropyl group	-H
				CZK (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-CH
CZL (a, b and c)	-3- (4-chloropyridazinyl)	-H	-H
				CZM (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Cl
CZN (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Br
				CZO (a, b and c)	-3- (4-chloropyridazinyl)	-H	-F
CZP (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CH

CZQ (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CF
				CZR (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCH
CZS (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCHCH
				CZT (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCF
CZU (a, b and c)	-3- (4-chloropyridazinyl)	-H	-tert-butyl
				CZV (a, b and c)	-3- (4-chloropyridazinyl)	-H	-isopropyl group
CZW(a，b and c)	-3- (4-methylpyridazinyl)	-Cl	-H
				CZX (a, b and c)	-3- (4-methylpyridazinyl)	-Br	-H
CZY (a, b and c)	-3- (4-methylpyridazinyl)	-F	-H
				CZZ (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-H
DAA (a, b and c)	-3- (4-methylpyridazinyl)	-CF	-H
				DAB (a, b and c)	-3- (4-methylpyridazinyl)	-OCH	-H
DAC (a, b and c)	-3- (4-methylpyridazinyl)	-OCHCH	-H
				DAD (a, b and c)	-3- (4-methylpyridazinyl)	-OCF	-H
DAE (a, b and c)	-3- (4-methylpyridazinyl)	-tert-butyl	-H
				DAF (a, b and c)	-3- (4-methylpyridazinyl)	-isopropyl group	-H
DAG (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-CH
				DAH (a, b and c)	-3- (4-methylpyridazinyl)	-H	-H
DAI (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Cl
				DAJ (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Br
DAK (a, b and c)	-3- (4-methylpyridazinyl)	-H	-F
				DAL (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CH
DAM (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CF
				DAN (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCH
DAO (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCHCH
				DAP(aB and c)	-3- (4-methylpyridazinyl)	-H	-OCF
DAQ (a, b and c)	-3- (4-methylpyridazinyl)	-H	-tert-butyl

DAR (a, b and c)	-3- (4-methylpyridazinyl)	-H	-isopropyl group
				DAS (a, b and c)	-4-thiazanyl	-Cl	-H
DAT (a, b and c)	-4-thiazanyl	-Br	-H
				DAU (a, b and c)	-4-thiazanyl	-F	-H
DAV (a, b and c)	-4-thiazanyl	-CH	-H
				DAW (a, b and c)	-4-thiazanyl	-CF	-H
DAX (a, b and c)	-4-thiazanyl	-OCH	-H
				DAY (a, b and c)	-4-thiazanyl	-OCHCH	-H
DAZ (a, b and c)	-4-thiazanyl	-OCF	-H
				DBA (a, b and c)	-4-thiazanyl	-tert-butyl	-H
DBB (a, b and c)	-4-thiazanyl	-isopropyl group	-H
				DBC (a, b and c)	-4-thiazanyl	-CH	-CH
DBD (a, b and c)	-4-thiazanyl	-H	-H
				DBE (a, b and c)	-4-thiazanyl	-H	-Cl
DBF (a, b and c)	-4-thiazanyl	-H	-Br
				DBG (a, b and c)	-4-thiazanyl	-H	-F
DBH (a, b and c)	-4-thiazanyl	-H	-CH
				DBI (a, b and c)	-4-thiazanyl	-H	-CF
DBJ (a, b and c)	-4-thiazanyl	-H	-OCH
				DBK (a, b and c)	-4-thiazanyl	-H	-OCHCH
DBL (a, b and c)	-4-thiazanyl	-H	-OCF
				DBM (a, b and c)	-4-thiazanyl	-H	-tert-butyl
DBN (a, b and c)	-4-thiazanyl	-H	-isopropyl group
				DBO (a, b and c)	-5- (4-chloro-thiazanyl)	-Cl	-H
DBP (a, b and c)	-5- (4-chloro-thiazanyl)	-Br	-H
				DBQ (a, b and c)	-5- (4-chloro-thiazanyl)	-F	-H
DBR (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-H

DBS (a, b and c)	-5- (4-chloro-thiazanyl)	-CF	-H
				DBT (a, b and c)	-5- (4-chloro-thiazanyl)	-OCH	-H
DBU (a, b and c)	-5- (4-chloro-thiazanyl)	-OCHCH	-H
				DBV (a, b and c)	-5- (4-chloro-thiazanyl)	-OCF	-H
DBW (a, b and c)	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
				DBX (a, b and c)	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
DBY (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-CH
				DBZ (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-H
DCA (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Cl
				DCB (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Br
DCC (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-F
				DCD (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CH
DCE (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CF
				DCF (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCH
DCG (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCHCH
				DCH (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCF
DCI (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
				DCJ (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-isopropyl group
DCK (a, b and c)	-5- (4-methylthiozanyl)	-Cl	-H
				DCL (a, b and c)	-5- (4-methylthiozanyl)	-Br	-H
DCM (a, b and c)	-5- (4-methylthiozanyl)	-F	-H
				DCN (a, b and c)	-5- (4-methylthiozanyl)	-CH	-H
DCO (a, b and c)	-5- (4-methylthiozanyl)	-CF	-H
				DCP (a, b and c)	-5- (4-methylthiozanyl)	-OCH	-H
DCQ (a, b and c)	-5- (4-methylthiozanyl)	-OCHCH	-H
				DCR (a, b and c)	-5- (4-methylthiozanyl)	-OCF	-H
DCS (a, b and c)	-5- (4-methylthiozanyl)	-tert-butyl	-H

DCT (a, b and c)	-5- (4-methylthiozanyl)	-isopropyl group	-H
				DCU (a, b and c)	-5- (4-methylthiozanyl)	-CH	-CH
DCV (a, b and c)	-5- (4-methylthiozanyl)	-H	-H
				DCW (a, b and c))	-5- (4-methylthiozanyl)	-H	-Cl
DCX (a, b and c)	-5- (4-methylthiozanyl)	-H	-Br
				DCY (a, b and c)	-5- (4-methylthiozanyl)	-H	-F
DCZ (a, b and c)	-5- (4-methylthiozanyl)	-H	-CH
				DDA (a, b and c)	-5- (4-methylthiozanyl)	-H	-CF
DDB (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCH
				DDC (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCHCH
DDD (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCF
				DDE (a, b and c)	-5- (4-methylthiozanyl)	-H	-tert-butyl
DDF (a, b and c)	-5- (4-methylthiozanyl)	-H	-isopropyl group

"a" indicates that the benzoxazole piperazine compound is racemic.

"b" indicates that the carbon atom of the piperazine attached to the methyl group is in the R configuration.

"c" indicates that the carbon atom of the piperazine attached to the methyl group is in the S configuration.

TABLE IX

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				DDG	-2-pyridazinyl radical	-Cl	-H
DDH	-2-pyridazinyl radical	-Br	-H
				DDI	-2-pyridazinyl radical	-F	-H
DDJ	-2-pyridazinyl radical	-CH	-H
				DDK	-2-pyridazinyl radical	-CF	-H
DDL	-2-pyridazinyl radical	-OCH	-H
				DDM	-2-pyridazinyl radical	-OCHCH	-H
DDN	-2-pyridazinyl radical	-OCF	-H
				DDO	-2-pyridazinyl radical	-tert-butyl	-H
DDP	-2-pyridazinyl radical	-isopropyl group	-H
				DDQ	-2-pyridazinyl radical	-CH	-CH
DDR	-2-pyridazinyl radical	-H	-H
				DDS	-2-pyridazinyl radical	-H	-Cl
DDT	-2-pyridazinyl radical	-H	-Br
				DDU	-2-pyridazinyl radical	-H	-F
DDV	-2-pyridazinyl radical	-H	-CH
				DDW	-2-pyridazinyl radical	-H	-CF
DDX	-2-pyridazinyl radical	-H	-OCH
				DDY	-2-pyridazinyl radical	-H	-OCHCH
DDZ	-2-pyridazinyl radical	-H	-OCF
				DEA	-2-pyridazinyl radical	-H	-tert-butyl
DEB	-2-pyridazinyl radical	-H	-isopropyl group
				DEC	-3- (4-chloropyridazinyl)	-Cl	-H
DED	-3- (4-chloropyridazinyl)	-Br	-H
				DEE	-3- (4-chloropyridazinyl)	-F	-H
DEF	-3- (4-chloropyridazinyl)	-CH	-H

DEG	-3- (4-chloropyridazinyl)	-CF	-H
				DEH	-3- (4-chloropyridazinyl)	-OCH	-H
DEI	-3- (4-chloropyridazinyl)	-OCHCH	-H
				DEJ	-3- (4-chloropyridazinyl)	-OCF	-H
DEK	-3- (4-chloropyridazinyl)	-tert-butyl	-H
				DEL	-3- (4-chloropyridazinyl)	-isopropyl group	-H
DEM	-3- (4-chloropyridazinyl)	-CH	-CH
				DEN	-3- (4-chloropyridazinyl)	-H	-H
DEO	-3- (4-chloropyridazinyl)	-H	-Cl
				DEP	-3- (4-chloropyridazinyl)	-H	-Br
DEQ	-3- (4-chloropyridazinyl)	-H	-F
				DER	-3- (4-chloropyridazinyl)	-H	-CH
DES	-3- (4-chloropyridazinyl)	-H	-CF
				DET	-3- (4-chloropyridazinyl)	-H	-OCH
DEU	-3- (4-chloropyridazinyl)	-H	-OCHCH
				DEV	-3- (4-chloropyridazinyl)	-H	-OCF
DEW	-3- (4-chloropyridazinyl)	-H	-tert-butyl
				DEX	-3- (4-chloropyridazinyl)	-H	-isopropyl group
DEY	-3- (4-methylpyridazinyl)	-Cl	-H
				DEZ	-3- (4-methylpyridazinyl)	-Br	-H
DFA	-3- (4-methylpyridazinyl)	-F	-H
				DFB	-3- (4-methylpyridazinyl)	-CH	-H
DFC	-3- (4-methylpyridazinyl)	-CF	-H
				DFD	-3- (4-methyl pyridazinyl)	-OCH	-H
DFE	-3- (4-methylpyridazinyl)	-OCHCH	-H
				DFF	-3- (4-methylpyridazinyl)	-OCF	-H
DFG	-3- (4-methylpyridazinyl)	-tert-butyl	-H

DFH	-3- (4-methylpyridazinyl)	-isopropyl group	-H
				DFI	-3- (4-methylpyridazinyl)	-CH	-CH
DFJ	-3- (4-methylpyridazinyl)	-H	-H
				DFK	-3- (4-methylpyridazinyl)	-H	-Cl
DFL	-3- (4-methylpyridazinyl)	-H	-Br
				DFM	-3- (4-methylpyridazinyl)	-H	-F
DFN	-3- (4-methylpyridazinyl)	-H	-CH
				DFO	-3- (4-methylpyridazinyl)	-H	-CF
DFP	-3- (4-methylpyridazinyl)	-H	-OCH
				DFQ	-3- (4-methylpyridazinyl)	-H	-OCHCH
DFR	-3- (4-methylpyridazinyl)	-H	-OCF
				DFS	-3- (4-methylpyridazinyl)	-H	-tert-butyl
DFT	-3- (4-methylpyridazinyl)	-H	-isopropyl group
				DFU	-4-thiazanyl	-Cl	-H
DFV	-4-thiazanyl	-Br	-H
				DFW	-4-thiazanyl	-F	-H
DFX	-4-thiazanyl	-CH	-H
				DFY	-4-thiazanyl	-CF	-H
DFZ	-4-thiazanyl	-OCH	-H
				DGA	-4-thiazanyl	-OCHCH	-H
DGB	-4-thiazanyl	-OCF	-H
				DGC	-4-thiazanyl	-tert-butyl	-H
DGD	-4-thiazanyl	-isopropyl group	-H
				DGE	-4-thiazanyl	-CH	-CH
DGF	-4-thiazanyl	-H	-H
				DGG	-4-thiazanyl	-H	-Cl
DGH	-4-thiazanyl	-H	-Br
				DGI	-4-thiazanyl	-H	-F
DGJ	-4-thiazanyl	-H	-CH

DGK	-4-thiazanyl	-H	-CF
				DGL	-4-thiazanyl	-H	-OCH
DGM	-4-thiazanyl	-H	-OCHCH
				DGN	-4-thiazanyl	-H	-OCF
DGO	-4-thiazanyl	-H	-tert-butyl
				DGP	-4-thiazanyl	-H	-isopropyl group
DGQ	-5- (4-chloro-thiazanyl)	-Cl	-H
				DGR	-5- (4-chloro-thiazanyl)	-Br	-H
DGS	-5- (4-chloro-thiazanyl)	-F	-H
				DGT	-5- (4-chloro-thiazanyl)	-CH	-H
DGU	-5- (4-chloro-thiazanyl)	-CF	-H
				DGV	-5- (4-chloro-thiazanyl)	-OCH	-H
DGW	-5- (4-chloro-thiazanyl)	-OCHCH	-H
				DGX	-5- (4-chloro-thiazanyl)	-OCF	-H
DGY	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
				DGZ	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
DHA	-5- (4-chloro-thiazanyl)	-CH	-CH
				DHB	-5- (4-chloro-thiazanyl)	-H	-H
DHC	-5- (4-chloro-thiazanyl)	-H	-Cl
				DHD	-5- (4-chloro-thiazanyl)	-H	-Br
DHE	-5- (4-chloro-thiazanyl)	-H	-F
				DHF	-5- (4-chloro-thiazanyl)	-H	-CH
DHG	-5- (4-chloro-thiazanyl)	-H	-CF
				DHH	-5- (4-chloro-thiazanyl)	-H	-OCH
DHI	-5- (4-chloro-thiazanyl)	-H	-OCHCH
				DHJ	-5- (4-chloro-thiazanyl)	-H	-OCF
DHK	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
				DHL	-5- (4-chloro-thiazanyl)	-H	-isopropyl group

DHM	-5- (4-methylthiozanyl)	-Cl	-H
				DHN	-5- (4-methylthiozanyl)	-Br	-H
DHO	-5- (4-methylthiozanyl)	-F	-H
				DHP	-5- (4-methylthiozanyl)	-CH	-H
DHQ	-5- (4-methylthiozanyl)	-CF	-H
				DHR	-5- (4-methylthiozanyl)	-OCH	-H
DHS	-5- (4-methylthiozanyl)	-OCHCH	-H
				DHT	-5- (4-methylthiozanyl)	-OCF	-H
DHU	-5- (4-methylthiozanyl)	-tert-butyl	-H
				DHV	-5- (4-methylthiozanyl)	-isopropyl group	-H
DHW	-5- (4-methylthiozanyl)	-CH	-CH
				DHX	-5- (4-methylthiozanyl)	-H	-H
DHY	-5- (4-methylthiozanyl)	-H	-Cl
				DHZ	-5- (4-methylthiozanyl)	-H	-Br
DIA	-5- (4-methylthiozanyl)	-H	-F
				DIB	-5- (4-methylthiozanyl)	-H	-CH
DIC	-5- (4-methylthiozanyl)	-H	-CF
				DID	-5- (4-methylthiozanyl)	-H	-OCH
DIE	-5- (4-methylthiozanyl)	-H	-OCHCH
				DIF	-5- (4-methylthiozanyl)	-H	-OCF
DIG	-5- (4-methylthiozanyl)	-H	-tert-butyl
				DIH	-5- (4-methylthiozanyl)	-H	-isopropyl group

Table X

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				DII	-2- (3-chloropyridyl)	-Cl	-H
DIJ	-2- (3-chloropyridyl)	-Br	-H
				DIK	-2- (3-chloropyridyl)	-F	-H
DIL	-2- (3-chloropyridyl)	-CH	-H
				DIM	-2- (3-chloropyridyl)	-CF	-H
DIN	-2- (3-chloropyridyl)	-OCH	-H
				DIO	-2- (3-chloropyridyl)	-OCHCH	-H
DIP	-2- (3-chloropyridyl)	-OCF	-H
				DIQ	-2- (3-chloropyridyl)	-tert-butyl	-H
DIR	-2- (3-chloropyridyl)	-isopropyl group	-H
				DIS	-2- (3-chloropyridyl)	-CH	-CH
DIT	-2- (3-chloropyridyl)	-H	-H
				DIU	-2- (3-chloropyridyl)	-H	-Cl
DIV	-2- (3-chloropyridyl)	-H	-Br
				DIW	-2- (3-chloropyridyl)	-H	-F
DIX	-2- (3-chloropyridyl)	-H	-CH
				DIY	-2- (3-chloropyridyl)	-H	-CF

DIZ	-2- (3-chloropyridyl)	-H	-OCH
				DJA	-2- (3-chloropyridyl)	-H	-OCHCH
DJB	-2- (3-chloropyridyl)	-H	-OCF
				DJC	-2- (3-chloropyridyl)	-H	-tert-butyl
DJD	-2- (3-chloropyridyl)	-H	-isopropyl group
				DJE	-2- (3-methylpyridinyl)	-Cl	-H
DJF	-2- (3-methylpyridinyl)	-Br	-H
				DJG	-2- (3-methylpyridinyl)	-F	-H
DJH	-2- (3-methylpyridinyl)	-CH	-H
				DJI	-2- (3-methylpyridinyl)	-CF	-H
DJJ	-2- (3-methylpyridinyl)	-OCH	-H
				DJK	-2- (3-methylpyridinyl)	-OCHCH	-H
DJL	-2- (3-methylpyridinyl)	-OCF	-H
				DJM	-2- (3-methylpyridinyl)	-tert-butyl	-H
DJN	-2- (3-methylpyridinyl)	-isopropyl group	-H
				DJO	-2- (3-methylpyridinyl)	-CH	-CH
DJP	-2- (3-methylpyridinyl)	-H	-H
				DJQ	-2- (3-methylpyridinyl)	-H	-Cl
DJR	-2- (3-methylpyridinyl)	-H	-Br
				DJS	-2- (3-methylpyridinyl)	-H	-F
DJT	-2- (3-methylpyridinyl)	-H	-CH
				DJU	-2- (3-methylpyridinyl)	-H	-CF
DJV	-2- (3-methylpyridinyl)	-H	-OCH
				DJW	-2- (3-methylpyridinyl)	-H	-OCHCH
DJX	-2- (3-methylpyridinyl)	-H	-OCF
				DJY	-2- (3-methylpyridinyl)	-H	-tert-butyl
DJZ	-2- (3-methylpyridinyl)	-H	-isopropyl group

DKA	-2-(3-CF-pyridyl group)	-Cl	-H
				DKB	-2-(3-CF-pyridyl group)	-Br	-H
DKC	-2-(3-CF-pyridyl group)	-F	-H
				DKD	-2-(3-CF-pyridyl group)	-CH	-H
DKE	-2-(3-CF-pyridyl group)	-CF	-H
				DKF	-2-(3-CF-pyridyl group)	-OCH	-H
DKG	-2-(3-CF-pyridyl group)	-OCHCH	-H
				DKH	-2-(3-CF-pyridyl group)	-OCF	-H
DKI	-2-(3-CF-pyridyl group)	-tert-butyl	-H
				DKJ	-2-(3-CF-pyridyl group)	-isopropyl group	-H
DKK	-2-(3-CF-pyridyl group)	-CH	-CH
				DKL	-2-(3-CF-pyridyl group)	-H	-H
DKM	-2-(3-CF-pyridyl group)	-H	-Cl
				DKN	-2-(3-CF-pyridyl group)	-H	-Br
DKO	-2-(3-CF-pyridyl group)	-H	-F
				DKP	-2-(3-CF-pyridyl group)	-H	-CH
DKQ	-2-(3-CF-pyridyl group)	-H	-CF
				DkR	-2-(3-CF-pyridyl group)	-H	-OCH
DKS	-2-(3-CF-pyridyl group)	-H	-OCHCH
				DKT	-2-(3-CF-pyridyl group)	-H	-OCF
DKU	-2-(3-CF-pyridyl group)	-H	-tert-butyl
				DKV	-2-(3-CF-pyridyl group)	-H	-isopropyl group
DKW	-4- (5-chloropyrimidinyl)	-Cl	-H
				DKX	-4- (5-chloropyrimidinyl)	-Br	-H
DKY	-4- (5-chloropyrimidinyl)	-F	-H
				DKZ	-4- (5-chloropyrimidinyl)	-CH	-H
DLA	-4- (5-chloropyrimidinyl)	-CF	-H

DLB	-4- (5-chloropyrimidinyl)	-OCH	-H
				DLC	-4- (5-chloropyrimidinyl)	-OCHCH	-H
DLD	-4- (5-chloropyrimidinyl)	-OCF	-H
				DLE	-4- (5-chloropyrimidinyl)	-tert-butyl	-H
DLF	-4- (5-chloropyrimidinyl)	-isopropyl group	-H
				DLG	-4- (5-chloropyrimidinyl)	-CH	-CH
DLH	-4- (5-chloropyrimidinyl)	-H	-H
				DLI	-4- (5-chloropyrimidinyl)	-H	-Cl
DLJ	-4- (5-chloropyrimidinyl)	-H	-Br
				DLK	-4- (5-chloropyrimidinyl)	-H	-F
DLL	-4- (5-chloropyrimidinyl)	-H	-CH
				DLM	-4- (5-chloropyrimidinyl)	-H	-CF
DLN	-4- (5-chloropyrimidinyl)	-H	-OCH
				DLO	-4- (5-chloropyrimidinyl)	-H	-OCHCH
DLP	-4- (5-chloropyrimidinyl)	-H	-OCF
				DLQ	-4- (5-chloropyrimidinyl)	-H	-tert-butyl
DLR	-4- (5-chloropyrimidinyl)	-H	-isopropyl group
				DLS	-4- (5-methylpyrimidinyl)	-Cl	-H
DLT	-4- (5-methylpyrimidinyl)	-Br	-H
				DLU	-4- (5-methylpyrimidinyl)	-F	-H
DLV	-4- (5-methylpyrimidinyl)	-CH	-H
				DLW	-4- (5-methylpyrimidinyl)	-CF	-H
DLX	-4- (5-methylpyrimidinyl)	-OCH	-H
				DLY	-4- (5-methylpyrimidinyl)	-OCHCH	-H
DLZ	-4- (5-methylpyrimidinyl)	-OCF	-H
				DMA	-4- (5-methylpyrimidinyl)	-tert-butyl	-H
DMB	-4- (5-methylpyrimidinyl)	-isopropyl group	-H

DMC	-4- (5-methylpyrimidinyl)	-CH	-CH
				DMD	-4- (5-methylpyrimidinyl)	-H	-H
DME	-4- (5-methylpyrimidinyl)	-H	-Cl
				DMF	-4- (5-methylpyrimidinyl)	-H	-Br
DMG	-4- (5-methylpyrimidinyl)	-H	-F
				DMH	-4- (5-methylpyrimidinyl)	-H	-CH
DMI	-4- (5-methylpyrimidinyl)	-H	-CF
				DMJ	-4- (5-methylpyrimidinyl)	-H	-OCH
DMK	-4- (5-methylpyrimidinyl)	-H	-OCHCH
				DML	-4- (5-methylpyrimidinyl)	-H	-OCF
DMM	-4- (5-methylpyrimidinyl)	-H	-tert-butyl
				DMN	-4- (5-methylpyrimidinyl)	-H	-isopropyl group
DMO	-2-pyrazinyl radical	-Cl	-H
				DMP	-2-pyrazinyl radical	-Br	-H
DMQ	-2-pyrazinyl radical	-F	-H
				DMR	-2-pyrazinyl radical	-CH	-H
DMS	-2-pyrazinyl radical	-CF	-H
				DMT	-2-pyrazinyl radical	-OCH	-H
DMU	-2-pyrazinyl radical	-OCHCH	-H
				DMV	-2-pyrazinyl radical	-OCF	-H
DMW	-2-pyrazinyl radical	-tert-butyl	-H
				DMX	-2-pyrazinyl radical	-isopropyl group	-H
DMY	-2-pyrazinyl radical	-CH	-CH
				DMZ	-2-pyrazinyl radical	-H	-H
DNA	-2-pyrazinyl radical	-H	-Cl
				DNB	-2-pyrazinyl radical	-H	-Br
DNC	-2-pyrazinyl radical	-H	-F

DND	-2-pyrazinyl radical	-H	-CH
				DNE	-2-pyrazinyl radical	-H	-CF
DNF	-2-pyrazinyl radical	-H	-OCH
				DNG	-2-pyrazinyl radical	-H	-OCHCH
DNH	-2-pyrazinyl radical	-H	-OCF
				DNI	-2-pyrazinyl radical	-H	-tert-butyl
DNJ	-2-pyrazinyl radical	-H	-isopropyl group
				DNK	-2- (3-chloropyrazinyl)	-Cl	-H
DNL	-2- (3-chloropyrazinyl)	-Br	-H
				DNM	-2- (3-chloropyrazinyl)	-F	-H
DNN	-2- (3-chloropyrazinyl)	-CH	-H
				DNO	-2- (3-chloropyrazinyl)	-CF	-H
DNP	-2- (3-chloropyrazinyl)	-OCH	-H
				DNQ	-2- (3-chloropyrazinyl)	-OCHCH	-H
DNR	-2- (3-chloropyrazinyl)	-OCF	-H
				DNS	-2- (3-chloropyrazinyl)	-tert-butyl	-H
DNT	-2- (3-chloropyrazinyl)	-isopropyl group	-H
				DNU	-2- (3-chloropyrazinyl)	-CH	-CH
DNV	-2- (3-chloropyrazinyl)	-H	-H
				DNW	-2- (3-chloropyrazinyl)	-H	-Cl
DNX	-2- (3-chloropyrazinyl)	-H	-Br
				DNY	-2- (3-chloropyrazinyl)	-H	-F
DNZ	-2- (3-chloropyrazinyl)	-H	-CH
				DOA	-2- (3-chloropyrazinyl)	-H	-CF
DOB	-2- (3-chloropyrazinyl)	-H	-OCH
				DOC	-2- (3-chloropyrazinyl)	-H	-OCHCH
DOD	-2- (3-chloropyrazinyl)	-H	-OCF

DOE	-2- (3-chloropyrazinyl)	-H	-tert-butyl
				DOF	-2- (3-chloropyrazinyl)	-H	-isopropyl group
DOG	-2- (3-methylpyrazinyl)	-Cl	-H
				DOH	-2- (3-methylpyrazinyl)	-Br	-H
DOI	-2- (3-methylpyrazinyl)	-F	-H
				DOJ	-2- (3-methylpyrazinyl)	-CH	-H
DOK	-2- (3-methylpyrazinyl)	-CF	-H
				DOL	-2- (3-methylpyrazinyl)	-OCH	-H
DOM	-2- (3-methylpyrazinyl)	-OCHCH	-H
				DON	-2- (3-methylpyrazinyl)	-OCF	-H
DOO	-2- (3-methylpyrazinyl)	-tert-butyl	-H
				DOP	-2- (3-methylpyrazinyl)	-isopropyl group	-H
DOQ	-2- (3-methylpyrazinyl)	-CH	-CH
				DOR	-2- (3-methylpyrazinyl)	-H	-H
DOS	-2- (3-methylpyrazinyl))	-H	-Cl
				DOT	-2- (3-methylpyrazinyl)	-H	-Br
DOU	-2- (3-methylpyrazinyl)	-H	-F
				DOV	-2- (3-methylpyrazinyl)	-H	-CH
DOW	-2- (3-methylpyrazinyl)	-H	-CF
				DOX	-2- (3-methylpyrazinyl)	-H	-OCH
DOY	-2- (3-methylpyrazinyl)	-H	-OCHCH
				DOZ	-2- (3-methylpyrazinyl)	-H	-OCF
DPA	-2- (3-methylpyrazinyl)	-H	-tert-butyl
				DPB	-2- (3-methylpyrazinyl)	-H	-isopropyl group
DPC	-2-pyridazinyl radical	-Cl	-H
				DPD	-2-pyridazinyl radical	-Br	-H
DPE	-2-pyridazinyl radical	-F	-H

DPF	-2-pyridazinyl radical	-CH	-H
				DPG	-2-pyridazinyl radical	-CF	-H
DPH	-2-pyridazinyl radical	-OCH	-H
				DPI	-2-pyridazinyl radical	-OCHCH	-H
DPJ	-2-pyridazinyl radical	-OCF	-H
				DPK	-2-pyridazinyl radical	-tert-butyl	-H
DPL	-2-pyridazinyl radical	-isopropyl group	-H
				DPM	-2-pyridazinyl radical	-CH	-CH
DPN	-2-pyridazinyl radical	-H	-H
				DPO	-2-pyridazinyl radical	-H	-Cl
DPP	-2-pyridazinyl radical	-H	-Br
				DPQ	-2-pyridazinyl radical	-H	-F
DPR	-2-pyridazinyl radical	-H	-CH
				DPS	-2-pyridazinyl radical	-H	-CF
DPT	-2-pyridazinyl radical	-H	-OCH
				DPU	-2-pyridazinyl radical	-H	-OCHCH
DPV	-2-pyridazinyl radical	-H	-OCF
				DPW	-2-pyridazinyl radical	-H	-tert-butyl
DPX	-2-pyridazinyl radical	-H	-isopropyl group
				DPY	-3- (4-chloropyridazinyl)	-Cl	-H
DPZ	-3- (4-chloropyridazinyl)	-Br	-H
				DQA	-3- (4-chloropyridazinyl)	-F	-H
DQB	-3- (4-chloropyridazinyl)	-CH	-H
				DQC	-3- (4-chloropyridazinyl)	-CF	-H
DQD	-3- (4-chloropyridazinyl)	-OCH	-H
				DQE	-3- (4-chloropyridazinyl)	-OCHCH	-H
DQF	-3- (4-chloropyridazinyl)	-OCF	-H

DQG	-3- (4-chloropyridazinyl)	-tert-butyl	-H
				DQH	-3- (4-chloropyridazinyl)	-isopropyl group	-H
DQI	-3- (4-chloropyridazinyl)	-CH	-CH
				DQJ	-3- (4-chloropyridazinyl)	-H	-H
DQK	-3- (4-chloropyridazinyl)	-H	-Cl
				DQL	-3- (4-chloropyridazinyl)	-H	-Br
DQM	-3- (4-chloropyridazinyl)	-H	-F
				DQN	-3- (4-chloropyridazinyl)	-H	-CH
DQO	-3- (4-chloropyridazinyl)	-H	-CF
				DQP	-3- (4-chloropyridazinyl)	-H	-OCH
DQQ	-3- (4-chloropyridazinyl)	-H	-OCHCH
				DQR	-3- (4-chloropyridazinyl)	-H	-OCF
DQS	-3- (4-chloropyridazinyl)	-H	-tert-butyl
				DQT	-3- (4-chloropyridazinyl)	-H	-isopropyl group
DQU	-3- (4-methylpyridazinyl)	-Cl	-H
				DQV	-3- (4-methylpyridazinyl)	-Br	-H
DQW	-3- (4-methylpyridazinyl)	-F	-H
				DQX	-3- (4-methylpyridazinyl)	-CH	-H
DQY	-3- (4-methylpyridazinyl)	-CF	-H
				DQZ	-3- (4-methylpyridazinyl)	-OCH	-H
DRA	-3- (4-methylpyridazinyl)	-OCHCH	-H
				DRB	-3- (4-methylpyridazinyl)	-OCF	-H
DRC	-3- (4-methylpyridazinyl)	-tert-butyl	-H
				DRD	-3- (4-methylpyridazinyl)	-isopropyl group	-H
DRE	-3- (4-methylpyridazinyl)	-CH	-CH
				DRF	-3- (4-methylpyridazinyl)	-H	-H
DRG	-3- (4-methylpyridazinyl)	-H	-Cl

DRH	-3- (4-methylpyridazinyl)	-H	-Br
				DRI	-3- (4-methylpyridazinyl)	-H	-F
DRJ	-3- (4-methylpyridazinyl)	-H	-CH
				DRK	-3- (4-methylpyridazinyl)	-H	-CF
DRL	-3- (4-methylpyridazinyl)	-H	-OCH
				DRM	-3- (4-methylpyridazinyl)	-H	-OCHCH
DRN	-3- (4-methylpyridazinyl)	-H	-OCF
				DRO	-3- (4-methylpyridazinyl)	-H	-tert-butyl
DRP	-3- (4-methylpyridazinyl)	-H	-isopropyl group
				DRQ	-4-thiazanyl	-Cl	-H
DRR	-4-thiazanyl	-Br	-H
				DRS	-4-thiazanyl	-F	-H
DRT	-4-thiazanyl	-CH	-H
				DRU	-4-thiazanyl	-CF	-H
DRV	-4-thiazanyl	-OCH	-H
				DRW	-4-thiazanyl	-OCHCH	-H
DRX	-4-thiazanyl	-OCF	-H
				DRY	-4-thiazanyl	-tert-butyl	-H
DRZ	-4-thiazanyl	-isopropyl group	-H
				DSA	-4-thiazanyl	-CH	-CH
DSB	-4-thiazanyl	-H	-H
				DSC	-4-thiazanyl	-H	-Cl
DSD	-4-thiazanyl	-H	-Br
				DSE	-4-thiazanyl	-H	-F
DSF	-4-thiazanyl	-H	-CH
				DSG	-4-thiazanyl	-H	-CF
DSH	-4-thiazanyl	-H	-OCH
				DSI	-4-thiazanyl	-H	-OCHCH
DSJ	-4-thiazanyl	-H	-OCF

DSK	-4-thiazanyl	-H	-tert-butyl
				DSL	-4-thiazanyl	-H	-isopropyl group
DSM	-5- (4-chloro-thiazanyl)	-Cl	-H
				DSN	-5- (4-chloro-thiazanyl)	-Br	-H
DSO	-5- (4-chloro-thiazanyl)	-F	-H
				DSP	-5- (4-chloro-thiazanyl)	-CH	-H
DSQ	-5- (4-chloro-thiazanyl)	-CF	-H
				DSR	-5- (4-chloro-thiazanyl)	-OCH	-H
DSS	-5- (4-chloro-thiazanyl)	-OCHCH	-H
				DST	-5- (4-chloro-thiazanyl)	-OCF	-H
DSU	-5- (4-chloro-thiaza)nyl)	-tert-butyl	-H
				DSV	-5- (4-chloro-thiazanyl)	Isopropyl group	-H
DSW	-5- (4-chloro-thiazanyl)	-CH	-CH
				DSX	-5- (4-chloro-thiazanyl)	-H	-H
DSY	-5- (4-chloro-thiazanyl)	-H	-Cl
				DSZ	-5- (4-chloro-thiazanyl)	-H	-Br
DTA	-5- (4-chloro-thiazanyl)	-H	-F
				DTB	-5- (4-chloro-thiazanyl)	-H	-CH
DTC	-5- (4-chloro-thiazanyl)	-H	-CF
				DTD	-5- (4-chloro-thiazanyl)	-H	-OCH
DTE	-5- (4-chloro-thiazanyl)	-H	-OCHCH
				DTF	-5- (4-chloro-thiazanyl)	-H	-OCF
DTG	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
				DTH	-5- (4-chloro-thiazanyl)	-H	-isopropyl group
DTI	-5- (4-methylthiozanyl)	-Cl	-H
				DTJ	-5- (4-methylthiozanyl)	-Br	-H
DTK	-5- (4-methylthiozanyl)	-F	-H

DTL	-5- (4-methylthiozanyl)	-CH	-H
				DTM	-5- (4-methylthiozanyl)	-CF	-H
DTN	-5- (4-methylthiozanyl)	-OCH	-H
				DTO	-5- (4-methylthiozanyl)	-OCHCH	-H
DTP	-5- (4-methylthiozanyl)	-OCF	-H
				DTQ	-5- (4-methylthiozanyl)	-tert-butyl	-H
DTR	-5- (4-methylthiozanyl)	-isopropyl group	-H
				DTS	-5- (4-methylthiozanyl)	-CH	-CH
DTT	-5- (4-methylthiozanyl)	-H	-H
				DTU	-5- (4-methylthiozanyl)	-H	-Cl
DTV	-5- (4-methylthiozanyl)	-H	-Br
				DTW	-5- (4-methylthiozanyl)	-H	-F
DTX	-5- (4-methylthiozanyl)	-H	-CH
				DTY	-5- (4-methylthiozanyl)	-H	-CF
DTZ	-5- (4-methylthiozanyl)	-H	-OCH
				DUA	-5- (4-methylthiozanyl)	-H	-OCHCH
DUB	-5- (4-methylthiozanyl)	-H	-OCF
				DUC	-5- (4-methylthiozanyl)	-H	-tert-butyl
DUD	-5- (4-methylthiozanyl)	-H	-isopropyl group

TABLE XI

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				DUE (a, b and c)	-2-pyridazinyl radical	-Cl	-H
DUF (a, b and c)	-2-pyridazinyl radical	-Br	-H
				DUG (a, b and c)	-2-pyridazinyl radical	-F	-H
DUH (a, b and c)	-2-pyridazinyl radical	-CH	-H
				DUI (a, b and c)	-2-pyridazinyl radical	-CF	-H
DUJ (a, b and c)	-2-pyridazinyl radical	-OCH	-H
				DUK (a, b and c)	-2-pyridazinyl radical	-OCHCH	-H
DUL (a, b and c)	-2-pyridazinyl radical	-OCF	-H
				DUM (a, b and c)	-2-pyridazinyl radical	-tert-butyl	-H
DUN (a, b and c)	-2-pyridazinyl radical	-isopropyl group	-H
				DUO (a, b and c)	-2-pyridazinyl radical	-CH	-CH
DUP (a, b and c)	-2-pyridazinyl radical	-H	-H
				DUQ (a, b and c)	-2-pyridazinyl radical	-H	-Cl
DUR (a, b and c)	-2-pyridazinyl radical	-H	-Br
				DUS (a, b and c)	-2-pyridazinyl radical	-H	-F

DUT (a, b and c)	-2-pyridazinyl radical	-H	-CH
				DUU (a, b and c)	-2-pyridazinyl radical	-H	-CF
DUV (a, b and c)	-2-pyridazinyl radical	-H	-OCH
				DUW (a, b and c)	-2-pyridazinyl radical	-H	-OCHCH
DUX (a, b and c)	-2-pyridazinyl radical	-H	-OCF
				DUY (a, b and c)	-2-pyridazinyl radical	-H	-tert-butyl
DUZ (a, b and c)	-2-pyridazinyl radical	-H	-isopropyl group
				DVA (a, b and c)	-3- (4-chloro pyridazinyl)	-Cl	-H
DVB (a, b and c)	-3- (4-chloropyridazinyl)	-Br	-H
				DVC (a, b and c)	-3- (4-chloropyridazinyl)	-F	-H
DVD (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-H
				DVE (a, b and c)	-3- (4-chloropyridazinyl)	-CF	-H
DVF (a, b and c)	-3- (4-chloropyridazinyl)	-OCH	-H
				DVG (a, b and c)	-3- (4-chloropyridazinyl)	-OCHCH	-H
DVH (a, b and c)	-3- (4-chloropyridazinyl)	-OCF	-H
				DVI (a, b and c)	-3- (4-chloropyridazinyl)	-tert-butyl	-H
DVJ (a, b and c)	-3- (4-chloropyridazinyl)	-isopropyl group	-H
				DVK (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-CH
DVL (a, b and c)	-3- (4-chloropyridazinyl)	-H	-H
				DVM (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Cl
DVN (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Br
				DVO (a, b and c)	-3- (4-chloropyridazinyl)	-H	-F
DVP (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CH
				DVQ (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CF
DVR (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCH
				DVS (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCHCH
DVT (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCF

DVU (a, b and c)	-3- (4-chloropyridazinyl)	-H	-tert-butyl
				DVV (a, b and c)	-3- (4-chloropyridazinyl)	-H	-isopropyl group
DVW (a, b and c)	-3- (4-methylpyridazinyl)	-Cl	-H
				DVX (a, b and c)	-3- (4-methylpyridazinyl)	-Br	-H
DVY (a, b and c)	-3- (4-methylpyridazinyl)	-F	-H
				DVZ (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-H
DWA (a, b and c)	-3- (4-methylpyridazinyl)	-CF	-H
				DWB (a, b and c)	-3- (4-methylpyridazinyl)	-OCH	-H
DWC (a, b and c)	-3- (4-methylpyridazinyl)	-OCHCH	-H
				DWD (a, b and c)	-3- (4-methylpyridazinyl)	-OCF	-H
DWE (a, b and c)	-3- (4-methylpyridazinyl)	-tert-butyl	-H
				DWF (a, b and c)	-3- (4-methylpyridazinyl)	-isopropyl group	-H
DWG (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-CH
				DWH (a, b and c)	-3- (4-methylpyridazinyl)	-H	-H
DWI (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Cl
				DWJ (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Br
DWK (a, b and c)	-3- (4-methylpyridazinyl)	-H	-F
				DWL (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CH
DWM (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CF
				DWN (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCH
DWO (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCHCH
				DWP (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCF
DWQ (a, b and c)	-3- (4-methylpyridazinyl)	-H	-tert-butyl
				DWR (a, b and c)	-3- (4-methylpyridazinyl)	-H	-isopropyl group
DWS (a, b and c)	-4-thiazanyl	-Cl	-H
				DWT (a, b and c)	-4-thiazanyl	-Br	-H
DWU (a, b and c)	-4-thiazanyl	-F	-H

DWV (a, b and c)	-4-thiazanyl	-CH	-H
				DWW (a, b and c)	-4-thiazanyl	-CF	-H
DWX (a, b and c)	-4-thiazanyl	-OCH	-H
				DWY (a, b and c)	-4-thiazanyl	-OCHCH	-H
DWZ (a, b and c)	-4-thiazanyl	-OCF	-H
				DXA (a, b and c)	-4-thiazanyl	-tert-butyl	-H
DXB (a, b and c)	-4-thiazanyl	-isopropyl group	-H
				DXC (a, b and c)	-4-thiazanyl	-CH	-CH
DXD (a, b and c)	-4-thiazanyl	-H	-H
				DXE (a, b and c)	-4-thiazanyl	-H	-Cl
DXF (a, b and c)	-4-thiazanyl	-H	-Br
				DXG (a, b and c)	-4-thiazanyl	-H	-F
DXH (a, b and c)	-4-thiazanyl	-H	-CH
				DXI (a, b and c)	-4-thiazanyl	-H	-CF
DXJ (a, b and c)	-4-thiazanyl	-H	-OCH
				DXK (a, b and c)	-4-thiazanyl	-H	-OCHCH
DXL (a, b and c)	-4-thiazanyl	-H	-OCF
				DXM (a, b and c)	-4-thiazanyl	-H	-tert-butyl
DXN (a, b and c)	-4-thiazanyl	-H	-isopropyl group
				DXO (a, b and c)	-5- (4-chloro-thiazanyl)	-Cl	-H
DXP (a, b and c)	-5- (4-chloro-thiazanyl)	-Br	-H
				DXQ (a, b and c)	-5- (4-chloro-thiazanyl)	-F	-H
DXR (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-H
				DXS (a, b and c)	-5- (4-chloro-thiazanyl)	-CF	-H
DXT (a, b and c)	-5- (4-chloro-thiazanyl)	-OCH	-H
				DXU (a, b and c)	-5- (4-chloro-thiazanyl)	-OCHCH	-H
DXV (a, b and c)	-5- (4-chloro-thiazanyl)	-OCF	-H

DXW (a, b and c)	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
				DXX (a, b and c)	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
DXY (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-CH
				DXZ (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-H
DYA (a, b and c)	-5- (4-chlorothiaz)anyl)	-H	-Cl
				DYB (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Br
DYC (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-F
				DYD (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CH
DYE (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CF
				DYF (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCH
DYG (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCHCH
				DYH (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCF
DYI (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
				DYJ (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-isopropyl group
DYK (a, b and c)	-5- (4-methylthiozanyl)	-Cl	-H
				DYL (a, b and c)	-5- (4-methylthiozanyl)	-Br	-H
DYM (a, b and c)	-5- (4-methylthiozanyl)	-F	-H
				DYN (a, b and c)	-5- (4-methylthiozanyl)	-CH	-H
DYO (a, b and c)	-5- (4-methylthiozanyl)	-CF	-H
				DYP (a, b and c)	-5- (4-methylthiozanyl)	-OCH	-H
DYQ (a, b and c)	-5- (4-methylthiozanyl)	-OCHCH	-H
				DYR (a, b and c)	-5- (4-methylthiozanyl)	-OCF	-H
DYS (a, b and c)	-5- (4-methylthiozanyl)	-tert-butyl	-H
				DYT (a, b and c)	-5- (4-methylthiozanyl)	-isopropyl group	-H
DYU (a, b and c)	-5- (4-methylthiozanyl)	-CH	-CH
				DYV (a, b and c)	-5- (4-methylthiozanyl)	-H	-H
DYW (a, b and c)	-5- (4-methylthiozanyl)	-H	-Cl

DYX (a, b and c)	-5- (4-methylthiozanyl)	-H	-Br
				DYY (a, b and c)	-5- (4-methylthiozanyl)	-H	-F
DYZ (a, b and c)	-5- (4-methylthiozanyl)	-H	-CH
				DZA (a, b and c)	-5- (4-methylthiozanyl)	-H	-CF
DZB (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCH
				DZC (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCHCH
DZD (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCF
				DZE (a, b and c)	-5- (4-methyl)thiazanyl)	-H	-tert-butyl
DZF (a, b and c)	-5- (4-methylthiozanyl)	-H	-isopropyl group

"a" indicates that the benzoxazole piperazine compound is racemic.

"b" indicates that the carbon atom of the piperazine attached to the methyl group is in the R configuration.

"c" indicates that the carbon atom of the piperazine attached to the methyl group is in the S configuration.

TABLE XII

And pharmaceutically acceptable salts thereof, wherein:

Compound (I)	Ar	R	R
				DZG (a, b and c)	-2- (3-chloropyridyl)	-Cl	-H
DZH (a, b and c)	-2- (3-chloropyridyl)	-Br	-H
				DZI (a, b and c)	-2- (3-chloropyridyl)	-F	-H
DZJ (a, b and c)	-2- (3-chloropyridyl)	-CH	-H

DZK (a, b and c)	-2- (3-chloropyridyl)	-CF	-H
				DZL (a, b and c)	-2- (3-chloropyridyl)	-OCH	-H
DZM (a, b and c)	-2- (3-chloropyridyl)	-OCHCH	-H
				DZN (a, b and c)	-2- (3-chloropyridyl)	-OCF	-H
DZO (a, b and c)	-2- (3-chloropyridyl)	-tert-butyl	-H
				DZP (a, b and c)	-2- (3-chloropyridyl)	-isopropyl group	-H
DZQ (a, b and c)	-2- (3-chloropyridyl)	-CH	-CH
				DZR (a, b and c)	-2- (3-chloropyridyl)	-H	-H
DZS (a, b and c)	-2- (3-chloropyridyl)	-H	-Cl
				DZT (a, b and c)	-2- (3-chloropyridyl)	-H	-Br
DZU (a, b and c)	-2- (3-chloropyridyl)	-H	-F
				DZV (a, b and c)	-2- (3-chloropyridyl)	-H	-CH
DZW (a, b and c)	-2- (3-chloropyridyl)	-H	-CF
				DZX(a，b and c)	-2- (3-chloropyridyl)	-H	-OCH
DZY (a, b and c)	-2- (3-chloropyridyl)	-H	-OCHCH
				DZZ (a, b and c)	-2- (3-chloropyridyl)	-H	-OCF
EAA (a, b and c)	-2- (3-chloropyridyl)	-H	-tert-butyl
				EAB (a, b and c)	-2- (3-chloropyridyl)	-H	-isopropyl group
EAC (a, b and c)	-2- (3-methylpyridinyl)	-Cl	-H
				BAD (a, b and c)	-2- (3-methylpyridinyl)	-Br	-H
EAE (a, b and c)	-2- (3-methylpyridinyl)	-F	-H
				EAF (a, b and c)	-2- (3-methylpyridinyl)	-CH	-H
EAG (a, b and c)	-2- (3-methylpyridinyl)	-CF	-H
				EAH (a, b and c)	-2- (3-methylpyridinyl)	-OCH	-H
EAI (a, b and c)	-2- (3-methylpyridinyl)	-OCHCH	-H
				EAJ (a, b and c)	-2- (3-methylpyridinyl)	-OCF	-H
EAK (a, b and c)	-2- (3-methylpyridinyl)	-tert-butyl	-H

EAL (a, b and c)	-2- (3-methylpyridinyl)	-isopropyl group	-H
				EAM (a, b and c)	-2- (3-methylpyridinyl)	-CH	-CH
EAN (a, b and c)	-2- (3-methylpyridinyl)	-H	-H
				EAO (a, b and c)	-2- (3-methylpyridine)Pyridyl radical)	-H	-Cl
EAP (a, b and c)	-2- (3-methylpyridinyl)	-H	-Br
				EAQ (a, b and c)	-2- (3-methylpyridinyl)	-H	-F
EAR (a, b and c)	-2- (3-methylpyridinyl)	-H	-CH
				EAS (a, b and c)	-2- (3-methylpyridinyl)	-H	-CF
EAT (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCH
				EAU (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCHCH
EAV (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCF
				EAW (a, b and c)	-2- (3-methylpyridinyl)	-H	-tert-butyl
EAX (a, b and c)	-2- (3-methylpyridinyl)	-H	-isopropyl group
				EAY (a, b and c)	-2-(3-CF-pyridyl group)	-Cl	-H
EAZ (a, b and c)	-2-(3-CF-pyridyl group)	-Br	-H
				EBA (a, b and c)	-2-(3-CF-pyridyl group)	-F	-H
EBB (a, b and c)	-2-(3-CF-pyridyl group)	-CH	-H
				EBC (a, b and c)	-2-(3-CF-pyridyl group)	-CF	-H
EBD (a, b and c)	-2-(3-CF-pyridyl group)	-OCH	-H
				EBE (a, b and c)	-2-(3-CF-pyridyl group)	-OCHCH	-H
EBF (a, b and c)	-2-(3-CF-pyridyl group)	-OCF	-H
				EBG (a, b and c)	-2-(3-CF-pyridyl group)	-tert-butyl	-H
EBH (a, b and c)	-2-(3-CF-pyridyl group)	-isopropyl group	-H
				EBI (a, b and c)	-2-(3-CF-pyridyl group)	-CH	-CH
EBJ (a, b and c)	-2-(3-CF-pyridyl group)	-H	-H
				EBK (a, b and c)	-2-(3-CF-pyridyl group)	-H	-Cl
EBL (a, b and c)	-2-(3-CF-pyridyl group)	-H	-Br

EBM (a, b and c)	-2-(3-CF-pyridyl group)	-H	-F
				EBN (a, b and c)	-2-(3-CF-pyridyl group)	-H	-CH
EBO (a, b and c)	-2-(3-CF-pyridyl group)	-H	-CF
				EBP (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCH
EBQ (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCHCH
				EBR (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCF
EBS (a, b and c)	-2-(3-CF-pyridyl group)	-H	-tert-butyl
				EBT (a, b and c)	-2-(3-CF-pyridyl group)	-H	-isopropyl group
EBU (a, b and c)	-4- (5-chloropyrimidinyl)	-Cl	-H
				EBV (a, b and c)	-4- (5-chloropyrimidinyl)	-Br	-H
EBW (a, b and c)	-4- (5-chloropyrimidinyl)	-F	-H
				EBX (a, b and c)	-4- (5-chloropyrimidinyl)	-CH	-H
EBY (a, b and c)	-4- (5-chloropyrimidinyl)	-CF	-H
				EBZ (a, b and c)	-4- (5-chloropyrimidinyl)	-OCH	-H
ECA (a, b and c)	-4- (5-chloropyrimidinyl)	-OCHCH	-H
				ECB (a, b and c)	-4- (5-chloropyrimidinyl)	-OCF	-H
ECC (a, b and c)	-4- (5-chloropyrimidinyl)	-tert-butyl	-H
				ECD (a, b and c)	-4- (5-chloropyrimidinyl)	-isopropyl group	-H
ECE (a, b and c)	-4- (5-chloropyrimidinyl)	-CH	-CH
				ECF (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-H
ECG (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-Cl
				ECH (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-Br
ECI (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-F
				ECJ (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-CH
ECK (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-CF
				ECL (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCH
ECM (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCHCH

ECN (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCF
				ECO (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-tert-butyl
ECP (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-isopropyl group
				ECQ (a, b and c)	-4- (5-methylpyrimidinyl)	-Cl	-H
ECR (a, b and c)	-4- (5-methylpyrimidinyl)	-Br	-H
				ECS (a, b and c)	-4- (5-methylpyrimidinyl)	-F	-H
ECT (a, b and c)	-4- (5-methylpyrimidinyl)	-CH	-H
				ECU (a, b and c)	-4- (5-methylpyrimidinyl)	-CF	-H
ECV (a, b and c)	-4- (5-methylpyrimidinyl)	-OCH	-H
				ECW (a, b and c)	-4- (5-methylpyrimidinyl)	-OCHCH	-H
ECX (a, b and c)	-4- (5-methylpyrimidinyl)	-OCF	-H
				ECY (a, b and c)	-4- (5-methylpyrimidinyl)	-tert-butyl	-H
ECZ (a, b and c)	-4- (5-methylpyrimidinyl)	-isopropyl group	-H
				EDA (a, b and c)	-4- (5-methylpyrimidinyl)	-CH	-CH
EDB (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-H
				EDC (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-Cl
EDD (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-Br
				EDE (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-F
EDF (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-CH
				EDG (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-CF
EDH (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCH
				EDI (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCHCH
EDJ (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCF
				EDK (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-tert-butyl
EDL (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-isopropyl group
				EDM (a, b and c)	-2-pyrazinyl radical	-Cl	-H
EDN (a, b and c)	-2-pyrazinyl radical	-Br	-H

EDO (a, b and c)	-2-pyrazinyl radical	-F	-H
				EDP (a, b and c)	-2-pyrazinyl radical	-CH	-H
EDQ (a, b and c)	-2-pyrazinyl radical	-CF	-H
				EDR (a, b and c)	-2-pyrazinyl radical	-OCH	-H
EDS (a, b and c)	-2-pyrazinyl radical	-OCHCH	-H
				EDT (a, b and c)	-2-pyrazinyl radical	-OCF	-H
EDU (a, b and c)	-2-pyrazinyl radical	-tert-butyl	-H
				EDV (a, b and c)	-2-pyrazinyl radical	-isopropyl group	-H
EDW (a, b and c)	-2-pyrazinyl radical	-CH	-CH
				EDX (a, b and c)	-2-pyrazinyl radical	-H	-H
EDY (a, b and c)	-2-pyrazinyl radical	-H	-Cl
				EDZ (a, b and c)	-2-pyrazinyl radical	-H	-Br
EEA (a, b and c)	-2-pyrazinyl radical	-H	-F
				EEB (a, b and c)	-2-pyrazinyl radical	-H	-CH
EEC (a, b and c)	-2-pyrazinyl radical	-H	-CF
				EED (a, b and c)	-2-pyrazinyl radical	-H	-OCH
EEE (a, b and c)	-2-pyrazinyl radical	-H	-OCHCH
				EEF (a, b and c)	-2-pyrazinyl radical	-H	-OCF
EEG (a, b and c)	-2-pyrazinyl radical	-H	-tert-butyl
				EEH (a, b and c)	-2-pyrazinyl radical	-H	-isopropyl group
EEI (a, b and c)	-2- (3-chloropyrazinyl)	-Cl	-H
				EEJ (a, b and c)	-2- (3-chloropyrazinyl)	-Br	-H
EEK (a, b and c)	-2- (3-chloropyrazinyl)	-F	-H
				EEL (a, b and c)	-2- (3-chloropyrazinyl)	-CH	-H
EEM (a, b and c)	-2- (3-chloropyrazinyl)	-CF	-H
				EEN (a, b and c)	-2- (3-chloropyrazinyl)	-OCH	-H
EEO (a, b and c)	-2- (3-chloropyrazinyl)	-OCHCH	-H

EEP (a, b and c)	-2- (3-chloropyrazinyl)	-OCF	-H
				EEQ (a, b and c)	-2- (3-chloropyrazinyl)	-tert-butyl	-H
EER (a, b and c)	-2- (3-chloropyrazinyl)	-isopropyl group	-H
				EES (a, b and c)	-2- (3-chloropyrazinyl)	-CH	-CH
EET (a, b and c)	-2- (3-chloropyrazinyl)	-H	-H
				EEU (a, b and c)	-2- (3-chloropyrazinyl)	-H	-Cl
EEV (a, b and c)	-2- (3-chloropyrazinyl)	-H	-Br
				EEW (a, b and c)	-2- (3-chloropyrazinyl)	-H	-F
EEX (a, b and c)	-2- (3-chloropyrazinyl)	-H	-CH
				EEY (a, b and c)	-2- (3-chloropyrazinyl)	-H	-CF
EEZ (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCH
				EFA (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCHCH
EFB (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCF
				EFC (a, b and c)	-2- (3-chloropyrazinyl)	-H	-tert-butyl
EFD (a, b and c)	-2- (3-chloropyrazinyl)	-H	-isopropyl group
				EFE (a, b and c)	-2- (3-methylpyrazinyl)	-Cl	-H
EFF (a, b and c)	-2- (3-methylpyrazinyl)	-Br	-H
				EFG (a, b and c)	-2- (3-methylpyrazinyl)	-F	-H
EFH (a, b and c)	-2- (3-methylpyrazinyl)	-CH	-H
				EFI (a, b and c)	-2- (3-methylpyrazinyl)	-CF	-H
EFJ (a, b and c)	-2- (3-methylpyrazinyl)	-OCH	-H
				EFK(a, b and c)	-2- (3-methylpyrazinyl)	-OCHCH	-H
EFL (a, b and c)	-2- (3-methylpyrazinyl)	-OCF	-H
				EFM (a, b and c)	-2- (3-methylpyrazinyl)	-tert-butyl	-H
EFN (a, b and c)	-2- (3-methylpyrazinyl)	-isopropyl group	-H
				EFO (a, b and c)	-2- (3-methylpyrazinyl)	-CH	-CH
EFP (a, b and c)	-2- (3-methylpyrazinyl)	-H	-H

EFQ (a, b and c)	-2- (3-methylpyrazinyl)	-H	-Cl
				EFR (a, b and c)	-2- (3-methylpyrazinyl)	-H	-Br
EFS (a, b and c)	-2- (3-methylpyrazinyl)	-H	-F
				EFT (a, b and c)	-2- (3-methylpyrazinyl)	-H	-CH
EFU (a, b and c)	-2- (3-methylpyrazinyl)	-H	-CF
				EFV (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCH
EFW (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCHCH
				EFX (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCF
EFY (a, b and c)	-2- (3-methylpyrazinyl)	-H	-tert-butyl
				EFZ (a, b and c)	-2- (3-methylpyrazinyl)	-H	-isopropyl group
EGA (a, b and c)	-2-pyridazinyl radical	-Cl	-H
				EGB (a, b and c)	-2-pyridazinyl radical	-Br	-H
EGC (a, b and c)	-2-pyridazinyl radical	-F	-H
				EGD (a, b and c)	-2-pyridazinyl radical	-CH	-H
EGE (a, b and c)	-2-pyridazinyl radical	-CF	-H
				EGF (a, b and c)	-2-pyridazinyl radical	-OCH	-H
EGG (a, b and c)	-2-pyridazinyl radical	-OCHCH	-H
				EGH (a, b and c)	-2-pyridazinyl radical	-OCF	-H
EGI (a, b and c)	-2-pyridazinyl radical	-tert-butyl	-H
				EGJ (a, b and c)	-2-pyridazinyl radical	-isopropyl group	-H
EGK (a, b and c)	-2-pyridazinyl radical	-CH	-CH
				EGL (a, b and c)	-2-pyridazinyl radical	-H	-H
EGM (a, b and c)	-2-pyridazinyl radical	-H	-Cl
				EGN (a, b and c)	-2-pyridazinyl radical	-H	-Br
EGO (a, b and c)	-2-pyridazinyl radical	-H	-F
				EGP (a, b and c)	-2-pyridazinyl radical	-H	-CH
EGQ (a, b and c)	-2-pyridazinyl radical	-H	-CF

EGR (a, b and c)	-2-pyridazinyl radical	-H	-OCH
				EGS (a, b and c)	-2-pyridazinyl radical	-H	-OCHCH
EGT (a, b and c)	-2-pyridazinyl radical	-H	-OCF
				EGU (a, b and c)	-2-pyridazinyl radical	-H	-tert-butyl
EGV (a, b and c)	-2-pyridazinyl radical	-H	-isopropyl group
				EGW (a, b and c)	-3- (4-chloropyridazinyl)	-Cl	-H
EGX (a, b and c)	-3- (4-chloropyridazinyl)	-Br	-H
				EGY (a, b and c)	-3- (4-chloropyridazinyl)	-F	-H
EGZ (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-H
				EHA (a, b and c)	-3- (4-chloropyridazinyl)	-CF	-H
EHB (a, b and c)	-3- (4-chloropyridazinyl)	-OCH	-H
				EHC (a, b and c)	-3- (4-chloropyridazinyl)	-OCHCH	-H
EHD (a, b and c)	-3- (4-chloropyridazinyl)	-OCF	-H
				EHE (a, b and c)	-3- (4-chloropyridazinyl)	-tert-butyl	-H
EHF (a, b and c)	-3- (4-chloropyridazinyl)	-isopropyl group	-H
				EHG (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-CH
EHH (a, b and c)	-3- (4-chloropyridazinyl)	-H	-H
				EHI (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Cl
EHJ (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Br
				EHK (a, b and c)	-3- (4-chloropyridazinyl)	-H	-F
EHL (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CH
				EHM (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CF
EHN (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCH
				EHO (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCHCH
EHP (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCF
				EHQ (a, b and c)	-3- (4-chloropyridazinyl)	-H	-tert-butyl
EHR (a, b and c)	-3- (4-chloropyridazinyl)	-H	-isopropyl group

EHS (a, b and c)	-3- (4-methylpyridazinyl)	-Cl	-H
				EHT (a, b and c)	-3- (4-methylpyridazinyl)	-Br	-H
EHU (a, b and c)	-3- (4-methylpyridazinyl)	-F	-H
				EHV (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-H
EHW (a, b and c)	-3- (4-methylpyridazinyl)	-CF	-H
				EHX (a, b and c)	-3- (4-methylpyridazinyl)	-OCH	-H
EHY (a, b and c)	-3- (4-methylpyridazinyl)	-OCHCH	-H
				EHZ (a, b and c)	-3- (4-methylpyridazinyl)	-OCF	-H
EIA (a, b and c)	-3- (4-methylpyridazinyl)	-tert-butyl	-H
				EIB (a, b and c)	-3- (4-methylpyridazinyl)	-isopropyl group	-H
EIC (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-CH
				EID (a, b and c)	-3- (4-methylpyridazinyl)	-H	-H
EIE (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Cl
				EIF (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Br
EIG (a, b and c)	-3- (4-methylpyridazinyl)	-H	-F
				EIH (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CH
EII (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CF
				EIJ (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCH
EIK (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCHCH
				EIL (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCF
EIM (a, b and c)	-3- (4-methylpyridazinyl)	-H	-tert-butyl
				EIN (a, b and c)	-3- (4-methylpyridazinyl)	-H	-isopropyl group
EIO (a, b and c)	-4-thiazanyl	-Cl	-H
				EIP (a, b and c)	-4-thiazanyl	-Br	-H
EIQ (a, b and c)	-4-thiazanyl	-F	-H
				EIR (a, b and c)	-4-thiazanyl	-CH	-H
EIS (a, b and c)	-4-thiazanyl	-CF	-H

EIT (a, b and c)	-4-thiazanyl	-OCH	-H
				EIU (a, b and c)	-4-thiazanyl	-OCHCH	-H
EIV (a, b and c)	-4-thiazanyl	-OCF	-H
				EIW (a, b and c)	-4-thiazanyl	-tert-butyl	-H
EIX (a, b and c)	-4-thiazanyl	-isopropyl group	-H
				EIY (a, b and c)	-4-thiazanyl	-CH	-CH
EIZ (a, b and c)	-4-thiazanyl	-H	-H
				EJA (a, b and c) -	4-thiazanyl	-H	-Cl
EJB (a, b and c)	-4-thiazanyl	-H	-Br
				EJC (a, b and c)	-4-thiazanyl	-H	-F
EJD (a, b and c)	-4-thiazanyl	-H	-CH
				EJE (a, b and c)	-4-thiazanyl	-H	-CF
EJF (a, b and c)	-4-thiazanyl	-H	-OCH
				EJG (a, b and c)	-4-thiazanyl	-H	-OCHCH
EJH (a, b and c)	-4-thiazanyl	-H	-OCF
				EJI (a, b and c)	-4-thiazanyl	-H	-tert-butyl
EJJ (a, b and c)	-4-thiazanyl	-H	-isopropyl group
				EJK (a, b and c)	-5- (4-chloro-thiazanyl)	-Cl	-H
EJL (a, b and c)	-5- (4-chloro-thiazanyl)	-Br	-H
				EJM (a, b and c)	-5- (4-chloro-thiazanyl)	-F	-H
EJN (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-H
				EJO (a, b and c)	-5- (4-chloro-thiazanyl)	-CF	-H
EJP (a, b and c)	-5- (4-chloro-thiazanyl)	-OCH	-H
				EJQ (a, b and c)	-5- (4-chloro-thiazanyl)	-OCHCH	-H
EJR (a, b and c)	-5- (4-chloro-thiazanyl)	-OCF	-H
				EJS (a, b and c)	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
EJT (a, b and c)	-5- (4-chloro-thiazanyl)	-isopropyl group	-H

EJU (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-CH
				EJV (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-H
EJW (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Cl
				EJX (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Br
EJY (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-F
				EJZ (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CH
EKA (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CF
				EKB (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCH
EKC (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCHCH
				EKD (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCF
EKE (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
				EKF (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-isopropyl group
EKG (a, b and c)	-5- (4-methylthiozanyl)	-Cl	-H
				EKH (a, b and c)	-5- (4-methylthiozanyl)	-Br	-H
EKI (a, b and c)	-5- (4-methylthiozanyl)	-F	-H
				EKJ (a, b and c)	-5- (4-methylthiozanyl)	-CH	-H
EKK (a, b and c)	-5- (4-methylthiozanyl)	-CF	-H
				EKL (a, b and c)	-5- (4-methylthiozanyl)	-OCH	-H
EKM (a, b and c)	-5- (4-methylthiozanyl)	-OCHCH	-H
				EKN (a, b and c)	-5- (4-methylthiozanyl)	-OCF	-H
EKO (a, b and c)	-5- (4-methylthiozanyl)	-tert-butyl	-H
				EKP (a, b and c)	-5- (4-methylthiozanyl)	-isopropyl group	-H
EKQ (a, b and c)	-5- (4-methylthiozanyl)	-CH	-CH
				EKR (a, b and c)	-5- (4-methylthiozanyl)	-H	-H
EKS (a, b and c)	-5- (4-methylthiozanyl)	-H	-Cl
				EKT (a, b and c)	-5- (4-methylthiozanyl)	-H	-Br
EKU (a, b and c)	-5- (4-methylthiozanyl)	-H	-F

EKV (a, b and c)	-5- (4-methylthiozanyl)	-H	-CH
				EKW (a, b and c)	-5- (4-methylthiozanyl)	-H	-CF
EKX (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCH
				EKY (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCHCH
EKZ (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCF
				ELA (a, b and c)	-5- (4-methylthiozanyl)	-H	-tert-butyl
ELB (a, b and c)	-5- (4-methylthiozanyl)	-H	-isopropyl group

"a" indicates that the benzoxazole piperazine compound is racemic.

"b" indicates that the carbon atom of the piperazine ring to which the methyl group is attached is in the R configuration.

"c" indicates that the carbon atom of the piperazine ring to which the methyl group is attached is in the S configuration.

TABLE XIII

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				ELC	-2- (3-chloropyridyl)	-Cl	-H
ELD	-2- (3-chloropyridyl)	-Br	-H
				ELE	-2- (3-chloropyridyl)	-F	-H
ELF	-2- (3-chloropyridyl)	-CH	-H
				ELG	-2- (3-chloropyridyl)	-CF	-H

ELH	-2- (3-chloropyridyl)	-OCH	-H
				ELI	-2- (3-chloropyridyl)	-OCHCH	-H
ELJ	-2- (3-chloropyridyl)	-OCF	-H
				ELK	-2- (3-chloropyridyl)	-tert-butyl	-H
ELL	-2- (3-chloropyridyl)	-isopropyl group	-H
				ELM	-2- (3-chloropyridyl)	-CH	-CH
ELN	-2- (3-chloropyridyl)	-H	-H
				ELO	-2- (3-chloropyridyl)	-H	-Cl
ELP	-2- (3-chloropyridyl)	-H	-Br
				ELQ	-2- (3-chloropyridyl)	-H	-F
ELR	-2- (3-chloropyridyl)	-H	-CH
				ELS	-2- (3-chloropyridyl)	-H	-CF
ELT	-2- (3-chloropyridyl)	-H	-OCH
				ELU	-2- (3-chloropyridyl)	-H	-OCHCH
ELV	-2- (3-chloropyridyl)	-H	-OCF
				ELW	-2- (3-chloropyridyl)	-H	-tert-butyl
ELX	-2- (3-chloropyridyl)	-H	-isopropyl group
				ELY	-2- (3-methylpyridinyl)	-Cl	-H
ELZ	-2- (3-methylpyridinyl)	-Br	-H
				EMA	-2- (3-methylpyridinyl)	-F	-H
EMB	-2- (3-methylpyridinyl)	-CH	-H
				EMC	-2- (3-methylpyridinyl)	-CF	-H
EMD	-2- (3-methylpyridinyl)	-OCH	-H
				EME	-2- (3-methylpyridinyl)	-OCHCH	-H
EMF	-2- (3-methylpyridinyl)	-OCF	-H
				EMG	-2- (3-methylpyridinyl)	-tert-butyl	-H
EMH	-2- (3-methylpyridinyl)	-isopropyl group	-H

EMI	-2- (3-methylpyridinyl)	-CH	-CH
				EMJ	-2- (3-methylpyridinyl)	-H	-H
EMK	-2- (3-methylpyridinyl)	-H	-Cl
				EML	-2- (3-methylpyridinyl)	-H	-Br
EMM	-2- (3-methylpyridinyl)	-H	-F
				EMN	-2- (3-methylpyridinyl)	-H	-CH
EMO	-2- (3-methylpyridinyl)	-H	-CF
				EMP	-2- (3-methylpyridinyl)	-H	-OCH
EMQ	-2- (3-methylpyridinyl)	-H	-OCHCH
				EMR	-2- (3-methylpyridinyl)	-H	-OCF
EMS	-2- (3-methylpyridinyl)	-H	-tert-butyl
				EMT	-2- (3-methylpyridinyl)	-H	Isopropyl group
EMU	-2-(3-CF-pyridyl group)	-Cl	-H
				EMV	-2-(3-CF-pyridyl group)	-Br	-H
EMW	-2-(3-CF-pyridyl group)	-F	-H
				EMX	-2-(3-CF-pyridyl group)	-CH	-H
EMY	-2-(3-CF-pyridyl group)	-CF	-H
				EMZ	-2-(3-CF-pyridyl group)	-OCH	-H
ENA	-2-(3-CF-pyridyl group)	-OCHCH	-H
				ENB	-2-(3-CF-pyridyl group)	-OCF	-H
ENC	-2-(3-CF-pyridyl group)	-tert-butyl	-H
				END	-2-(3-CF-pyridyl group)	-isopropyl group	-H
ENE	-2-(3-CF-pyridyl group)	-CH	-CH
				ENF	-2-(3-CF-pyridyl group)	-H	-H
ENG	-2-(3-CF-pyridyl group)	-H	-Cl
				ENH	-2-(3-CF-pyridyl group)	-H	-Br
ENI	-2-(3-CF-pyridyl group)	-H	-F

ENJ	-2-(3-CF-pyridyl group)	-H	-CH
				ENK	-2-(3-CF-pyridyl group)	-H	-CF
ENL	-2-(3-CF-pyridyl group)	-H	-OCH
				ENM	-2-(3-CF-pyridyl group)	-H	-OCHCH
ENN	-2-(3-CF-pyridyl group)	-H	-OCF
				ENO	-2-(3-CF-pyridyl group)	-H	-tert-butyl
ENP	-2-(3-CF-pyridyl group)	-H	-isopropyl group
				ENQ	-4- (5-chloropyrimidinyl)	-Cl	-H
ENR	-4- (5-chloropyrimidinyl)	-Br	-H
				ENS	-4- (5-chloropyrimidinyl)	-F	-H
ENT	-4- (5-chloropyrimidinyl)	-CH	-H
				ENU	-4- (5-chloropyrimidinyl)	-CF	-H
ENV	-4- (5-chloropyrimidinyl)	-OCH	-H
				ENW	-4- (5-chloropyrimidinyl)	-OCHCH	-H
ENX	-4- (5-chloropyrimidinyl)	-OCF	-H
				ENY	-4- (5-chloropyrimidinyl)	-tert-butyl	-H
ENZ	-4- (5-chloropyrimidinyl)	-isopropyl group	-H
				EOA	-4- (5-chloropyrimidinyl)	-CH	-CH
EOB	-4- (5-chloropyrimidinyl)	-H	-H
				EOC	-4- (5-chloropyrimidinyl)	-H	-Cl
EOD	-4- (5-chloropyrimidinyl)	-H	-Br
				EOE	-4- (5-chloropyrimidinyl)	-H	-F
EOF	-4- (5-chloropyrimidinyl)	-H	-CH
				EOG	-4- (5-chloropyrimidinyl)	-H	-CF
EOH	-4- (5-chloropyrimidinyl)	-H	-OCH
				EOI	-4- (5-chloropyrimidinyl)	-H	-OCHCH
EOJ	-4- (5-chloropyrimidinyl)	-H	-OCF

EOK	-4- (5-chloropyrimidinyl)	-H	-tert-butyl
				EOL	-4- (5-chloropyrimidinyl)	-H	-isopropyl group
EOM	-4- (5-methylpyrimidinyl)	-Cl	-H
				EON	-4- (5-methylpyrimidinyl)	-Br	-H
EOO	-4- (5-methylpyrimidinyl)	-F	-H
				EOP	-4- (5-methylpyrimidinyl)	-CH	-H
EOQ	-4- (5-methylpyrimidinyl)	-CF	-H
				EOR	-4- (5-methylpyrimidinyl)	-OCH	-H
EOS	-4- (5-methylpyrimidinyl)	-OCHCH	-H
				EOT	-4- (5-methylpyrimidinyl)	-OCF	-H
EOU	-4- (5-methylpyrimidinyl)	-tert-butyl	-H
				EOV	-4- (5-methylpyrimidinyl)	-isopropyl group	-H
EOW	-4- (5-methylpyrimidinyl)	-CH	-CH
				EOX	-4- (5-methylpyrimidinyl)	-H	-H
EOY	-4- (5-methylpyrimidinyl)	-H	-Cl
				EOZ	-4- (5-methylpyrimidinyl)	-H	-Br
EPA	-4- (5-methylpyrimidinyl)	-H	-F
				EPB	-4- (5-methylpyrimidinyl)	-H	-CH
EPC	-4- (5-methylpyrimidinyl)	-H	-CF
				EPD	-4- (5-methylpyrimidinyl)	-H	-OCH
EPE	-4- (5-methylpyrimidinyl)	-H	-OCHCH
				EPF	-4- (5-methylpyrimidinyl)	-H	-OCF
EPG	-4- (5-methylpyrimidinyl)	-H	-tert-butyl
				EPH	-4- (5-methylpyrimidinyl)	-H	-isopropyl group
EPI	-2-pyrazinyl radical	-Cl	-H
				EPJ	-2-pyrazinyl radical	-Br	-H
EPK	-2-pyrazinyl radical	-F	-H

EPL	-2-pyrazinyl radical	-CH	-H
				EPM	-2-pyrazinyl radical	-CF	-H
EPN	-2-pyrazinyl radical	-OCH	-H
				EPO	-2-pyrazinyl radical	-OCHCH	-H
EPP	-2-pyrazinyl radical	-OCF	-H
				EPQ	-2-pyrazinyl radical	-tert-butyl	-H
EPR	-2-pyrazinyl radical	-isopropyl group	-H
				EPS	-2-pyrazinyl radical	-CH	-CH
EPT	-2-pyrazinyl radical	-H	-H
				EPU	-2-pyrazinyl radical	-H	-Cl
EPV	-2-pyrazinyl radical	-H	-Br
				EPW	-2-pyrazinyl radical	-H	-F
EPX	-2-pyrazinyl radical	-H	-CH
				EPY	-2-pyrazinyl radical	-H	-CF
EPZ	-2-pyrazinyl radical	-H	-OCH
				EQA	-2-pyrazinyl radical	-H	-OCHCH
EQB	-2-pyrazinyl radical	-H	-OCF
				EQC	-2-pyrazinyl radical	-H	-tert-butyl
EQD	-2-pyrazinyl radical	-H	-isopropyl group
				EQE	-2- (3-chloropyrazinyl)	-Cl	-H
EQF	-2- (3-chloropyrazinyl)	-Br	-H
				EQG	-2- (3-chloropyrazinyl)	-F	-H
EQH	-2- (3-chloropyrazinyl)	-CH	-H
				EQI	-2- (3-chloropyrazinyl)	-CF	-H
EQJ	-2- (3-chloropyrazinyl)	-OCH	-H
				EQK	-2- (3-chloropyrazinyl)	-OCHCH	-H
EQL	-2- (3-chloropyrazinyl)	-OCF	H

EQM	-2- (3-chloropyrazinyl)	-tert-butyl	-H
				EQN	-2- (3-chloropyrazinyl)	-isopropyl group	-H
EQO	-2- (3-chloropyrazinyl)	-CH	-CH
				EQP	-2- (3-chloropyrazinyl)	-H	-H
EQQ	-2- (3-chloropyrazinyl)	-H	-Cl
				EQR	-2- (3-chloropyrazinyl)	-H	-Br
EQS	-2- (3-chloropyrazinyl)	-H	-F
				EQT	-2- (3-chloropyrazinyl)	-H	-CH
EQU	-2- (3-chloropyrazinyl)	-H	-CF
				EQV	-2- (3-chloropyrazinyl)	-H	-OCH
EQW	-2- (3-chloropyrazinyl)	-H	-OCHCH
				EQX	-2- (3-chloropyrazinyl)	-H	-OCF
EQY	-2- (3-chloropyrazinyl)	-H	-tert-butyl
				EQZ	-2- (3-chloropyrazinyl)	-H	-isopropyl group
ERA	-2- (3-methylpyrazinyl)	-Cl	-H
				ERB	-2- (3-methylpyrazinyl)	-Br	-H
ERC	-2- (3-methylpyrazinyl)	-F	-H
				ERD	-2- (3-methylpyrazinyl)	-CH	-H
ERE	-2- (3-methylpyrazinyl)	-CF	-H
				ERF	-2- (3-methylpyrazinyl)	-OCH	-H
ERG	-2- (3-methylpyrazinyl)	-OCHCH	-H
				ERH	-2- (3-methylpyrazinyl)	-OCF	-H
ERI	-2- (3-methylpyrazinyl)	-tert-butyl	-H
				ERJ	-2- (3-methylpyrazinyl)	-isopropyl group	-H
ERK	-2- (3-methylpyrazinyl)	-CH	-CH
				ERL	-2- (3-methylpyrazinyl)	-H	-H
ERM	-2- (3-methylpyrazinyl)	-H	-Cl

ERN	-2- (3-methylpyrazinyl)	-H	-Br
				ERO	-2- (3-methylpyrazinyl)	-H	-F
ERP	-2- (3-methylpyrazinyl)	-H	-CH
				ERQ	-2- (3-methylpyrazinyl)	-H	-CF
ERR	-2- (3-methylpyrazinyl)	-H	-OCH
				ERS	-2- (3-methylpyrazinyl)	-H	-OCHCH
ERT	-2- (3-methylpyrazinyl)	-H	-OCF
				ERU	-2- (3-methylpyrazinyl)	-H	-tert-butyl
ERV	-2- (3-methylpyrazinyl)	-H	-isopropyl group
				ERW	-2-pyridazinyl radical	-Cl	-H
ERX	-2-pyridazinyl radical	-Br	-H
				ERY	-2-pyridazinyl radical	-F	-H
ERZ	-2-pyridazinyl radical	-CH	-H
				ESA	-2-pyridazinyl radical	-CF	-H
ESB	-2-pyridazinyl radical	-OCH	-H
				ESC	-2-pyridazinyl radical	-OCHCH	-H
ESD	-2-pyridazinyl radical	-OCF	-H
				ESE	-2-pyridazinyl radical	-tert-butyl	-H
ESF	-2-pyridazinyl radical	-isopropyl group	-H
				ESG	-2-pyridazinyl radical	-CH	-CH
ESH	-2-pyridazinyl radical	-H	-H
				ESI	-2-pyridazinyl radical	-H	-Cl
ESJ	-2-pyridazinyl radical	-H	-Br
				ESK	-2-pyridazinyl radical	-H	-F
ESL	-2-pyridazinyl radical	-H	-CH
				ESM	-2-pyridazinyl radical	-H	-CF
ESN	-2-pyridazinyl radical	-H	-OCH

ESO	-2-pyridazinyl radical	-H	-OCHCH
				ESP	-2-pyridazinyl radical	-H	-OCF
ESQ	-2-pyridazinyl radical	-H	-tert-butyl
				ESR	-2-pyridazinyl radical	-H	-isopropyl group
ESS	-3- (4-chloropyridazinyl)	-Cl	-H
				EST	-3- (4-chloropyridazinyl)	-Br	-H
ESU	-3- (4-chloropyridazinyl)	-F	-H
				ESV	-3- (4-chloropyridazinyl)	-CH	-H
ESW	-3- (4-chloropyridazinyl)	-CF	-H
				ESX	-3- (4-chloropyridazinyl)	-OCH	-H
ESY	-3- (4-chloropyridazinyl)	-OCHCH	-H
				ESZ	-3- (4-chloropyridazinyl)	-OCF	-H
ETA	-3- (4-chloropyridazinyl)	-tert-butyl	-H
				ETB	-3- (4-chloropyridazinyl)	-isopropyl group	-H
ETC	-3- (4-chloropyridazinyl)	-CH	-CH
				ETD	-3- (4-chloropyridazinyl)	-H	-H
ETE	-3- (4-chloropyridazinyl)	-H	-Cl
				ETF	-3- (4-chloropyridazinyl)	-H	-Br
ETG	-3- (4-chloropyridazinyl)	-H	-F
				ETH	-3- (4-chloropyridazinyl)	-H	-CH
ETI	-3- (4-chloropyridazinyl)	-H	-CF
				ETJ	-3- (4-chloropyridazinyl)	-H	-OCH
ETK	-3- (4-chloropyridazinyl)	-H	-OCHCH
				ETL	-3- (4-chloropyridazinyl)	-H	-OCF
ETM	-3- (4-chloropyridazinyl)	-H	-tert-butyl
				ETN	-3- (4-chloropyridazinyl)	-H	-isopropyl group
ETO	-3- (4-chloropyridazinyl)	-Cl	-H

ETP	-3- (4-methylpyridazinyl)	-Br	-H
				ETQ	-3- (4-methylpyridazinyl)	-F	-H
ETR	-3- (4-methylpyridazinyl)	-CH	-H
				ETS	-3- (4-methylpyridazinyl)	-CF	-H
ETT	-3- (4-methylpyridazinyl)	-OCH	-H
				ETU	-3- (4-methylpyridazinyl)	-OCHCH	-H
ETV	-3- (4-methylpyridazinyl)	-OCF	-H
				ETW	-3- (4-methylpyridazinyl)	-tert-butyl	-H
ETX	-3- (4-methylpyridazinyl)	-isopropyl group	-H
				ETY	-3- (4-methylpyridazinyl)	-CH	-CH
ETZ	-3- (4-methylpyridazinyl)	-H	-H
				EUA	-3- (4-methylpyridazinyl)	-H	-Cl
EUB	-3- (4-methylpyridazinyl)	-H	-Br
				EUC	-3- (4-methylpyridazinyl)	-H	-F
EUD	-3- (4-methylpyridazinyl)	-H	-CH
				EUE	-3- (4-methylpyridazinyl)	-H	-CF
EUF	-3- (4-methylpyridazinyl)	-H	-OCH
				EUG	-3- (4-methylpyridazinyl)	-H	-OCHCH
EUH	-3- (4-methylpyridazinyl)	-H	-OCF
				EUI	-3- (4-methylpyridazinyl)	-H	-tert-butyl
EUJ	-3- (4-methylpyridazinyl)	-H	-isopropyl group
				EUK	-4-thiazanyl	-Cl	-H
EUL	-4-thiazanyl	-Br	-H
				EUM	-4-thiazanyl	-F	-H
EUN	-4-thiazanyl	-CH	-H
				EUO	-4-thiazanyl	-CF	-H
EUP	-4-thiazanyl	-OCH	-H
				EUQ	4-thiazanyl	-OCHCH	-H

EUR	-4-thiazanyl	-OCF	-H
				EUS	-4-thiazanyl	-tert-butyl	-H
EUT	-4-thiazanyl	-isopropyl group	-H
				EUU	-4-thiazanyl	-CH	-CH
EUV	-4-thiazanyl	-H	-H
				EUW	-4-thiazanyl	-H	-Cl
EUX	-4-thiazanyl	-H	-Br
				EUY	-4-thiazanyl	-H	-F
EUZ	-4-thiazanyl	-H	-CH
				EVA	-4-thiazanyl	-H	-CF
EVB	-4-thiazanyl	-H	-OCH
				EVC	-4-thiazanyl	-H	-OCHCH
EVD	-4-thiazanyl	-H	-OCF
				EVE	-4-thiazanyl	-H	-tert-butyl
EVF	-4-thiazanyl	-H	-isopropyl group
				EVG	-5- (4-chloro-thiazanyl)	-Cl	-H
EVH	-5- (4-chloro-thiazanyl)	-Br	-H
				EVI	-5- (4-chloro-thiazanyl)	-F	-H
EVJ	-5- (4-chloro-thiazanyl)	-CH	-H
				EVK	-5- (4-chloro-thiazanyl)	-CF	-H
EVL	-5- (4-chloro-thiazahyl)	-OCH	-H
				EVM	-5- (4-chloro-thiazanyl)	-OCHCH	-H
EVN	-5- (4-chloro-thiazanyl)	-OCF	-H
				EVO	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
EVP	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
				EVQ	-5- (4-chloro-thiazanyl)	-CH	-CH
EVR	-5- (4-chloro-thiazanyl)	-H	-H
				EVS	-5- (4-chloro-thiazanyl)	-H	-Cl
EVT	-5- (4-chloro-thiazanyl)	-H	-Br

EVU	-5- (4-chloro-thiazanyl)	-H	-F
				EVV	-5- (4-chloro-thiazanyl)	-H	-CH
EVW	-5- (4-chloro-thiazanyl)	-H	-CF
				EVX	-5- (4-chloro-thiazanyl)	-H	-OCH
EVY	-5- (4-chloro-thiazanyl)	-H	-OCHCH
				EVZ	-5- (4-chloro-thiazanyl)	-H	-OCF
EWA	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
				EWB	-5- (4-chloro-thiazanyl)	-H	-isopropyl group
EWC	-5- (4-methylthiozanyl)	-Cl	-H
				EWD	-5- (4-methylthiozanyl)	-Br	-H
EWE	-5- (4-methylthiozanyl)	-F	-H
				EWF	-5- (4-methylthiozanyl)	-CH	-H
EWG	-5- (4-methylthiozanyl)	-CF	-H
				EWH	-5- (4-methylthiozanyl)	-OCH	-H
EWI	-5- (4-methylthiozanyl)	-OCHCH	-H
				EWJ	-5- (4-methylthiozanyl)	-OCF	-H
EWK	-5- (4-methylthiozanyl)	-tert-butyl	-H
				EWL	-5- (4-methylthiozanyl)	-isopropyl group	-H
EWM	-5- (4-methylthiozanyl)	-CH	-CH
				EWN	-5- (4-methylthiozanyl)	-H	-H
EWO	-5- (4-methylthiozanyl)	-H	-Cl
				EWP	-5- (4-methylthiozanyl)	-H	-Br
EWQ	-5- (4-methylthiozanyl)	-H	-F
				EWR	-5- (4-methylthiozanyl)	-H	-CH
EWS	-5- (4-methylthiozanyl)	-H	-CF
				EWT	-5- (4-methylthiozanyl)	-H	-OCH
EWU	-5- (4-methylthiozanyl)	-H	-OCHCH

EWV	-5- (4-methylthiozanyl)	-H	-OCF
				EWW	-5- (4-methylthiozanyl)	-H	-tert-butyl
EWX	-5- (4-methylthiozanyl)	-H	-isopropyl group

TABLE XIV

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				EWY	-2- (3-chloropyridyl)	-Cl	-H
EWZ	-2- (3-chloropyridyl)	-Br	-H
				EXA	-2- (3-chloropyridyl)	-F	-H
EXB	-2- (3-chloropyridyl)	-CH	-H
				EXC	-2- (3-chloropyridyl)	-CF	-H
EXD	-2- (3-chloropyridyl)	-OCH	-H
				EXE	-2- (3-chloropyridyl)	-OCHCH	-H
EXF	-2- (3-chloropyridyl)	-OCF	-H
				EXG	-2- (3-chloropyridyl)	-tert-butyl	-H
EXH	-2- (3-chloropyridyl)	-isopropyl group	-H
				EXI	-2- (3-chloropyridyl)	-CH	-CH
EXJ	-2- (3-chloropyridyl)	-H	-H
				EXK	-2- (3-chloropyridyl)	-H	-Cl

EXL	-2- (3-chloropyridyl)	-H	-Br
				EXM	-2- (3-chloropyridyl)	-H	-F
EXN	-2- (3-chloropyridyl)	-H	-CH
				EXO	-2- (3-chloropyridyl)	-H	-CF
EXP	-2- (3-chloropyridyl)	-H	-OCH
				EXQ	-2- (3-chloropyridyl)	-H	-OCHCH
EXR	-2- (3-chloropyridyl)	-H	-OCF
				EXS	-2- (3-chloropyridyl)	-H	-tert-butyl
EXT	-2- (3-chloropyridyl)	-H	-isopropyl group
				EXU	-2- (3-methylpyridinyl)	-Cl	-H
EXV	-2- (3-methylpyridinyl)	-Br	-H
				EXW	-2- (3-methylpyridinyl)	-F	-H
EXX	-2- (3-methylpyridinyl)	-CH	-H
				EXY	-2- (3-methylpyridinyl)	-CF	-H
EXZ	-2- (3-methylpyridinyl)	-OCH	-H
				EYA	-2- (3-methylpyridinyl)	-OCHCH	-H
EYB	-2- (3-methylpyridinyl)	-OCF	-H
				EYC	-2- (3-methylpyridinyl)	-tert-butyl	-H
EYD	-2- (3-methylpyridinyl)	-isopropyl group	-H
				EYE	-2- (3-methylpyridinyl)	-CH	-CH
EYF	-2- (3-methylpyridinyl)	-H	-H
				EYG	-2- (3-methylpyridinyl)	-H	-Cl
EYH	-2- (3-methylpyridinyl)	-H	-Br
				EYI	-2- (3-methylpyridinyl)	-H	-F
EYJ	-2- (3-methylpyridinyl)	-H	-CH
				EYK	-2- (3-methylpyridinyl)	-H	-CF
EYL	-2- (3-methylpyridinyl)	-H	-OCH

EYM	-2- (3-methylpyridinyl)	-H	-OCHCH
				EYN	-2- (3-methylpyridinyl)	-H	-OCF
EYO	-2- (3-methylpyridinyl)	-H	-tert-butyl
				EYP	-2- (3-methylpyridinyl)	-H	-isopropyl group
EYQ	-2-(3-CF-pyridyl group)	-Cl	-H
				EYR	-2-(3-CF-pyridyl group)	-Br	-H
EYS	-2-(3-CF-pyridyl group)	-F	-H
				EYT	-2-(3-CF-pyridyl group)	-CH	-H
EYU	-2-(3-CF-pyridyl group)	-CF	-H
				EYV	-2-(3-CF-pyridyl group)	-OCH	-H
EYW	-2-(3-CF-pyridyl group)	-OCHCH	-H
				EYX	-2-(3-CF-pyridyl group)	-OCF	-H
EYY	-2-(3-CF-pyridyl group)	-tert-butyl	-H
				EYZ	-2-(3-CF-pyridyl group)	-isopropyl group	-H
EZA	-2-(3-CF-pyridyl group)	-CH	-CH
				EZB	-2-(3-CF-pyridyl group)	-H	-H
EZC	-2-(3-CF-pyridyl group)	-H	-Cl
				EZD	-2-(3-CF-pyridyl group)	-H	-Br
EZE	-2-(3-CF-pyridyl group)	-H	-F
				EZF	-2-(3-CF-pyridyl group)	-H	-CH
EZG	-2-(3-CF-pyridyl group)	-H	-CF
				EZH	-2-(3-CF-pyridyl group)	-H	-OCH
EZI	-2-(3-CF-pyridyl group)	-H	-OCHCH
				EZJ	-2-(3-CF-pyridyl group)	-H	-OCF
EZK	-2-(3-CF-pyridyl group)	-H	-tert-butyl
				EZL	-2-(3-CF-pyridyl group)	-H	-isopropyl group
EZM	-4- (5-chloropyrimidinyl)	-Cl	-H

EZN	-4- (5-chloropyrimidinyl)	-Br	-H
				EZO	-4- (5-chloropyrimidinyl)	-F	-H
EZP	-4- (5-chloropyrimidinyl)	-CH	-H
				EZQ	-4- (5-chloropyrimidinyl)	-CF	-H
EZR	-4- (5-chloropyrimidinyl)	-OCH	-H
				EZS	-4- (5-chloropyrimidinyl)	-OCHCH	-H
EZT	-4- (5-chloropyrimidinyl)	-OCF	-H
				EZU	-4- (5-chloropyrimidinyl)	-tert-butyl	-H
EZV	-4- (5-chloropyrimidinyl)	-isopropyl group	-H
				EZW	-4- (5-chloropyrimidinyl)	-CH	-CH
EZX	-4- (5-chloro)Substituted pyrimidyl group)	-H	-H
				EZY	-4- (5-chloropyrimidinyl)	-H	-Cl
EZZ	-4- (5-chloropyrimidinyl)	-H	-Br
				FAA	-4- (5-chloropyrimidinyl)	-H	-F
FAB	-4- (5-chloropyrimidinyl)	-H	-CH
				FAC	-4- (5-chloropyrimidinyl)	-H	-CF
FAD	-4- (5-chloropyrimidinyl)	-H	-OCH
				FAE	-4- (5-chloropyrimidinyl)	-H	-OCHCH
FAF	-4- (5-chloropyrimidinyl)	-H	-OCF
				FAG	-4- (5-chloropyrimidinyl)	-H	-tert-butyl
FAH	-4- (5-chloropyrimidinyl)	-H	-isopropyl group
				FAI	-4- (5-methylpyrimidinyl)	-Cl	-H
FAJ	-4- (5-methylpyrimidinyl)	-Br	-H
				FAK	-4- (5-methylpyrimidinyl)	-F	-H
FAL	-4- (5-methylpyrimidinyl)	-CH	-H
				FAM	-4- (5-methylpyrimidinyl)	-CF	-H
FAN	-4- (5-methylpyrimidinyl)	-OCH	-H

FAO	-4- (5-methylpyrimidinyl)	-OCHCH	-H
				FAP	-4- (5-methylpyrimidine)Pyridyl radical)	-OCF	-H
FAQ	-4- (5-methylpyrimidinyl)	-tert-butyl	-H
				FAR	-4- (5-methylpyrimidinyl)	-isopropyl group	-H
FAS	-4- (5-methylpyrimidinyl)	-CH	-CH
				FAT	-4- (5-methylpyrimidinyl)	-H	-H
FAU	-4- (5-methylpyrimidinyl)	-H	-Cl
				FAV	-4- (5-methylpyrimidinyl)	-H	-Br
FAW	-4- (5-methylpyrimidinyl)	-H	-F
				FAX	-4- (5-methylpyrimidinyl)	-H	-CH
FAY	-4- (5-methylpyrimidinyl)	-H	-CF
				FAZ	-4- (5-methylpyrimidinyl)	-H	-OCH
FBA	-4- (5-methylpyrimidinyl)	-H	-OCHCH
				FBB	-4- (5-methylpyrimidinyl)	-H	-OCF
FBC	-4- (5-methylpyrimidinyl)	-H	-tert-butyl
				FBD	-4- (5-methylpyrimidinyl)	-H	-isopropyl group
FBE	-2-pyrazinyl radical	-Cl	-H
				FBF	-2-pyrazinyl radical	-Br	-H
FBG	-2-pyrazinyl radical	-F	-H
				FBH	-2-pyrazinyl radical	-CH	-H
FBI	-2-pyrazinyl radical	-CF	-H
				FBJ	-2-pyrazinyl radical	-OCH	-H
FBK	-2-pyrazinyl radical	-OCHCH	-H
				FBL	-2-pyrazinyl radical	-OCF	-H
FBM	-2-pyrazinyl radical	-tert-butyl	-H
				FBN	-2-pyrazinyl radical	-isopropyl group	-H
FBO	-2-pyrazinyl radical	-CH	-CH

FBP	-2-pyrazinyl radical	-H	-H
				FBQ	-2-pyrazinyl radical	-H	-Cl
FBR	-2-pyrazinyl radical	-H	-Br
				FBS	-2-pyrazinyl radical	-H	-F
FBT	-2-pyrazinyl radical	-H	-CH
				FBU	-2-pyrazinyl radical	-H	-CF
FBV	-2-pyrazinyl radical	-H	-OCH
				FBW	-2-pyrazinyl radical	-H	-OCHCH
FBX	-2-pyrazinyl radical	-H	-OCF
				FBY	-2-pyrazinyl radical	-H	-tert-butyl
FBZ	-2-pyrazinyl radical	-H	-isopropyl group
				FCA	-2- (3-chloropyrazinyl)	-Cl	-H
FCB	-2- (3-chloropyrazinyl)	-Br	-H
				FCC	-2- (3-chloropyrazinyl)	-F	-H
FCD	-2- (3-chloropyrazinyl)	-CH	-H
				FCE	-2- (3-chloropyrazinyl)	-CF	-H
FCF	-2- (3-chloropyrazinyl)	-OCH	-H
				FCG	-2- (3-chloropyrazinyl)	-OCHCH	-H
FCH	-2- (3-chloropyrazinyl)	-OCF	-H
				FCI	-2- (3-chloropyrazinyl)	-tert-butyl	-H
FCJ	-2- (3-chloropyrazinyl)	-isopropyl group	-H
				FCK	-2- (3-chloropyrazinyl)	-CH	-CH
FCL	-2- (3-chloropyrazinyl)	-H	-H
				FCM	-2- (3-chloropyrazinyl)	-H	-Cl
FCN	-2- (3-chloropyrazinyl)	-H	-Br
				FCO	-2- (3-chloropyrazinyl)	-H	-F
FCP	-2- (3-chloropyrazinyl)	-H	-CH

FCQ	-2- (3-chloropyrazinyl)	-H	-CF
				FCR	-2- (3-chloropyrazinyl)	-H	-OCH
FCS	-2- (3-chloropyrazinyl)	-H	-OCHCH
				FCT	-2- (3-chloropyrazinyl)	-H	-OCF
FCU	-2- (3-chloropyrazinyl)	-H	-tert-butyl
				FCV	-2- (3-chloropyrazinyl)	-H	-isopropyl group
FCW	-2- (3-methylpyrazinyl)	-Cl	-H
				FCX	-2- (3-methylpyrazinyl)	-Br	-H
FCY	-2- (3-methylpyrazinyl)	-F	-H
				FCZ	-2- (3-methylpyrazinyl)	-CH	-H
FDA	-2- (3-methylpyrazinyl)	-CF	-H
				FDB	-2- (3-methylpyrazinyl)	-OCH	-H
FDC	-2- (3-methylpyrazinyl)	-OCHCH	-H
				FDD	-2- (3-methylpyrazinyl)	-OCF	-H
FDE	-2- (3-methylpyrazinyl)	-tert-butyl	-H
				FDF	-2- (3-methylpyrazinyl)	-isopropyl group	-H
FDG	-2- (3-methylpyrazinyl)	-CH	-CH
				FDH	-2- (3-methylpyrazinyl)	-H	-H
FDI	-2- (3-methylpyrazinyl)	-H	-Cl
				FDJ	-2- (3-methylpyrazinyl)	-H	-Br
FDK	-2- (3-methylpyrazinyl)	-H	-F
				FDL	-2- (3-methylpyrazinyl)	-H	-CH
FDM	-2- (3-methylpyrazinyl)	-H	-CF
				FDN	-2- (3-methylpyrazinyl)	-H	-OCH
FDO	-2- (3-methylpyrazinyl)	-H	-OCHCH
				FDP	-2- (3-methylpyrazinyl)	-H	-OCF
FDQ	-2- (3-methylpyrazinyl)	-H	-tert-butyl

FDR	-2- (3-methylpyrazinyl)	-H	-isopropyl group
				FDS	-2-pyridazinyl radical	-Cl	-H
FDT	-2-pyridazinyl radical	-Br	-H
				FDU	-2-pyridazinyl radical	-F	-H
FDV	-2-pyridazinyl radical	-CH	-H
				FDW	-2-pyridazinyl radical	-CF	-H
FDX	-2-pyridazinyl radical	-OCH	-H
				FDY	-2-pyridazinyl radical	-OCHCH	-H
FDZ	-2-pyridazinyl radical	-OCF	-H
				FEA	-2-pyridazinyl radical	-tert-butyl	-H
FEB	-2-pyridazinyl radical	-isopropyl group	-H
				FEC	-2-pyridazinyl radical	-CH	-CH
FED	-2-pyridazinyl radical	-H	-H
				FEE	-2-pyridazinyl radical	-H	-Cl
FEF	-2-pyridazinyl radical	-H	-Br
				FEG	-2-pyridazinyl radical	-H	-F
FEH	-2-pyridazinyl radical	-H	-CH
				FEI	-2-pyridazinyl radical	-H	-CF
FEJ	-2-pyridazinyl radical	-H	-OCH
				FEK	-2-pyridazinyl radical	-H	-OCHCH
FEL	-2-pyridazinyl radical	-H	-OCF
				FEM	-2-pyridazinyl radical	-H	-tert-butyl
FEN	-2-pyridazinyl radical	-H	-isopropyl group
				FEO	-3- (4-chloropyridazinyl)	-Cl	-H
FEP	-3- (4-chloropyridazinyl)	-Br	-H
				FEQ	-3- (4-chloropyridazinyl)	-F	-H
FER	-3- (4-chloropyridazinyl)	-CH	-H

FES	-3- (4-chloropyridazinyl)	-CF	-H
				FET	-3- (4-chloropyridazinyl)	-OCH	-H
FEU	-3- (4-chloropyridazinyl)	-OCHCH	-H
				FEV	-3- (4-chloropyridazinyl)	-OCF	-H
FEW	-3- (4-chloropyridazinyl)	-tert-butyl	-H
				FEX	-3- (4-chloropyridazinyl)	-isopropyl group	-H
FEY	-3- (4-chloropyridazinyl)	-CH	-CH
				FEZ	-3- (4-chloropyridazinyl)	-H	-H
FFA	-3- (4-chloropyridazinyl)	-H	-Cl
				FFB	-3- (4-chloropyridazinyl)	-H	-Br
FFC	-3- (4-chloropyridazinyl)	-H	-F
				FFD	-3- (4-chloropyridazinyl)	-H	-CH
FFE	-3- (4-chloropyridazinyl)	-H	-CF
				FFF	-3- (4-chloropyridazinyl)	-H	-OCH
FFG	-3- (4-chloropyridazinyl)	-H	-OCHCH
				FFH	-3- (4-chloropyridazinyl)	-H	-OCF
FFI	-3- (4-chloropyridazinyl)	-H	-tert-butyl
				FFJ	-3- (4-chloropyridazinyl)	-H	-isopropyl group
FFK	-3- (4-methylpyridazinyl)	-Cl	-H
				FFL	-3- (4-methylpyridazinyl)	-Br	-H
FFM	-3- (4-methylpyridazinyl)	-F	-H
				FFN	-3- (4-methylpyridazinyl)	-CH	-H
FFO	-3- (4-methylpyridazinyl)	-CF	-H
				FFP	-3- (4-methylpyridazinyl)	-OCH	-H
FFQ	-3- (4-methylpyridazinyl)	-OCHCH	-H
				FFR	-3- (4-methylpyridazinyl)	-OCF	-H
FFS	-3- (4-methylpyridazinyl)	-tert-butyl	-H

FFT	-3- (4-methylpyridazinyl)	-isopropyl group	-H
				FFU	-3- (4-methylpyridazinyl)	-CH	-CH
FFV	-3- (4-methylpyridazinyl)	-H	-H
				FFW	-3- (4-methylpyridazinyl)	-H	-Cl
FFX	-3- (4-methylpyridazinyl)	-H	-Br
				FFY	-3- (4-methylpyridazinyl)	-H	-F
FFZ	-3- (4-methylpyridazinyl)	-H	-CH
				FGA	-3- (4-methylpyridazinyl)	-H	-CF
FGB	-3- (4-methylpyridazinyl)	-H	-OCH
				FGC	-3- (4-methylpyridazinyl)	-H	-OCHCH
FGD	-3- (4-methylpyridazinyl)	-H	-OCF
				FGE	-3- (4-methylpyridazinyl)	-H	-tert-butyl
FGF	-3- (4-methylpyridazinyl)	-H	-isopropyl group
				FGG	-4-thiazanyl	-Cl	-H
FGH	-4-thiazanyl	-Br	-H
				FGI	-4-thiazanyl	-F	-H
FGJ	-4-thiazanyl	-CH	-H
				FGK	-4-thiazanyl	-CF	-H
FGL	-4-thiazanyl	-OCH	-H
				FGM	-4-thiazanyl	-OCHCH	-H
FGN	-4-thiazanyl	-OCF	-H
				FGO	-4-thiazanyl	-tert-butyl	-H
FGP	-4-thiazanyl	-isopropyl group	-H
				FGQ	-4-thiazanyl	-CH	-CH
FGR	-4-thiazanyl	-H	-H
				FGS	-4-thiazanyl	-H	-Cl
FGT	-4-thiazanyl	-H	-Br
				FGU	-4-thiazanyl	-H	-F
FGV	-4-thiazanyl	-H	-CH

FGW	-4-thiazanyl	-H	-CF
				FGX	-4-thiazanyl	-H	-OCH
FGY	-4-thiazanyl	-H	-OCHCH
				FGZ	-4-thiazanyl	-H	-OCF
FHA	-4-thiazanyl	-H	-tert-butyl
				FHB	-4-thiazanyl	-H	-isopropyl group
FHC	-5- (4-chloro-thiazanyl)	-Cl	-H
				FHD	-5- (4-chloro-thiazanyl)	-Br	-H
FHE	-5- (4-chloro-thiazanyl)	-F	-H
				FHF	-5- (4-chloro-thiazanyl)	-CH	-H
FHG	-5- (4-chloro-thiazanyl)	-CF	-H
				FHH	-5- (4-chloro-thiazanyl)	-OCH	-H
FHI	-5- (4-chloro-thiazanyl)	-OCHCH	-H
				FHJ	-5- (4-chloro-thiazanyl)	-OCF	-H
FHK	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
				FHL	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
FHM	-5- (4-chloro-thiazanyl)	-CH	-CH
				FHN	-5- (4-chloro-thiazanyl)	-H	-H
FHO	-5- (4-chloro-thiazanyl)	-H	-Cl
				FHP	-5- (4-chloro-thiazanyl)	-H	-Br
FHQ	-5- (4-chloro-thiazanyl)	-H	-F
				FHR	-5- (4-chloro-thiazanyl)	-H	-CH
FHS	-5- (4-chloro-thiazanyl)	-H	-CF
				FHT	-5- (4-chloro-thiazanyl)	-H	-OCH
FHU	-5- (4-chloro-thiazanyl)	-H	-OCHCH
				FHV	-5- (4-chloro-thiazanyl)	-H	-OCF
FHW	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
				FHX	-5- (4-chloro-thiazanyl)	-H	-isopropyl group

FHY	-5- (4-methylthiozanyl)	-Cl	-H
				FHZ	-5- (4-methylthiozanyl)	-Br	-H
FIA	-5- (4-methylthiozanyl)	-F	-H
				FIB	-5- (4-methylthiozanyl)	-CH	-H
FIC	-5- (4-methylthiozanyl)	-CF	-H
				FID	-5- (4-methylthiozanyl)	-OCH	-H
FIE	-5- (4-methylthiozanyl)	-OCHCH	-H
				FIF	-5- (4-methylthiozanyl)	-OCF	-H
FIG	-5- (4-methylthiozanyl)	-tert-butyl	-H
				FIH	-5-(4-Methyl thiazanyl)	-isopropyl group	-H
FII	-5- (4-methylthiozanyl)	-CH	-CH
				FIJ	-5- (4-methylthiozanyl)	-H	-H
FIK	-5- (4-methylthiozanyl)	-H	-Cl
				FIL	-5- (4-methylthiozanyl)	-H	-Br
FIM	-5- (4-methylthiozanyl)	-H	-F
				FIN	-5- (4-methylthiozanyl)	-H	-CH
FIO	-5- (4-methylthiozanyl)	-H	-CF
				FIP	-5- (4-methylthiozanyl)	-H	-OCH
FIQ	-5- (4-methylthiozanyl)	-H	-OCHCH
				FIR	-5- (4-methylthiozanyl)	-H	-OCF
FIS	-5- (4-methylthiozanyl)	-H	-tert-butyl
				FIT	-5- (4-methylthiozanyl)	-H	-isopropyl group

TABLE XV

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	Ar	R	R
				FIU (a, b and c)	-2- (3-chloropyridyl)	-Cl	-H
FIV (a, b and c)	-2- (3-chloropyridyl)	-Br	-H
				FIW (a, b and c)	-2- (3-chloropyridyl)	-F	-H
FIX (a, b and c)	-2- (3-chloropyridyl)	-CH	-H
				FIY (a, b and c)	-2- (3-chloropyridyl)	-CF	-H
FIZ (a, b and c)	-2- (3-chloropyridyl)	-OCH	-H
				FJA (a, b and c)	-2- (3-chloropyridyl)	-OCHCH	-H
FJB (a, b and c)	-2- (3-chloropyridyl)	-OCF	-H
				FJC (a, b and c)	-2- (3-chloropyridyl)	-tert-butyl	-H
FJD(a，b and c)	-2- (3-chloropyridyl)	-isopropyl group	-H
				FJE (a, b and c)	-2- (3-chloropyridyl)	-CH	-CH
FJF (a, b and c)	-2- (3-chloropyridyl)	-H	-H
				FJG (a, b and c)	-2- (3-chloropyridyl)	-H	-Cl
FJH (a, b and c)	-2- (3-chloropyridyl)	-H	-Br
				FJI (a, b and c)	-2- (3-chloropyridyl)	-H	-F
FJJ (a, b and c)	-2- (3-chloropyridyl)	-H	-CH

FJK (a, b and c)	-2- (3-chloropyridyl)	-H	-CF
				FJL (a, b and c)	-2- (3-chloropyridyl)	-H	-OCH
FJM (a, b and c)	-2- (3-chloropyridyl)	-H	-OCHCH
				FJN (a, b and c)	-2- (3-chloropyridyl)	-H	-OCF
FJO (a, b and c)	-2- (3-chloropyridyl)	-H	-tert-butyl
				FJP (a, b and c)	-2- (3-chloropyridyl)	-H	-isopropyl group
FJQ (a, b and c)	-2- (3-methylpyridinyl)	-Cl	-H
				FJR (a, b and c)	-2- (3-methylpyridinyl)	-Br	-H
FJS (a, b and c)	-2- (3-methylpyridinyl)	-F	-H
				FJT (a, b and c)	-2- (3-methylpyridinyl)	-CH	-H
FJU (a, b and c)	-2- (3-methylpyridinyl)	-CF	-H
				FJV (a, b and c)	-2- (3-methylpyridinyl)	-OCH	-H
FJW (a, b and c)	-2- (3-methylpyridinyl)	-OCHCH	-H
				FJX (a, b and c)	-2- (3-methylpyridinyl)	-OCF	-H
FJY (a, b and c)	-2- (3-methylpyridinyl)	-tert-butyl	-H
				FJZ (a, b and c)	-2- (3-methylpyridinyl)	-isopropyl group	-H
FKA (a, b and c)	-2- (3-methylpyridinyl)	-CH	-CH
				FKB (a, b and c)	-2- (3-methylpyridinyl)	-H	-H
FKC (a, b and c)	-2- (3-methylpyridinyl)	-H	-cl
				FKD (a, b and c)	-2- (3-methylpyridinyl)	-H	-Br
FKE (a, b and c)	-2- (3-methylpyridinyl)	-H	-F
				FKF (a, b and c)	-2- (3-methylpyridinyl)	-H	-CH
FKG (a, b and c)	-2- (3-methylpyridinyl)	-H	-CF
				FKH (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCH
FKI (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCHCH
				FKJ (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCF
FKK (a, b and c)	-2- (3-methylpyridinyl)	-H	-tert-butyl

FKL (a, b and c)	-2- (3-methylpyridinyl)	-H	-isopropyl group
				FKM (a, b and c)	-2-(3-CF-pyridyl group)	-Cl	-H
FKN (a, b and c)	-2-(3-CF-pyridyl group)	-Br	-H
				FKO (a, b and c)	-2-(3-CF-pyridyl group)	-F	-H
FKP (a, b and c)	-2-(3-CF-pyridyl group)	-CH	-H
				FKQ (a, b and c)	-2-(3-CF-pyridyl group)	-CF	-H
FKR (a, b and c)	-2-(3-CF-pyridyl group)	-OCH	-H
				FKS (a, b and c)	-2-(3-CF-pyridyl group)	-OCHCH	-H
FKT (a, b and c)	-2-(3-CF-pyridyl group)	-OCF	-H
				FKU (a, b and c)	-2-(3-CF-pyridyl group)	-tert-butyl	-H
FKV (a, b and c)	-2-(3-CF-pyridyl group)	-isopropyl group	-H
				FKW (a, b and c)	-2-(3-CF-pyridyl group)	-CH	-CH
FKX (a, b and c)	-2-(3-CF-pyridyl group)	-H	-H
				FKY (a, b and c)	-2-(3-CF-pyridyl group)	-H	-Cl
FKZ (a, b and c)	-2-(3-CF-pyridyl group)	-H	-Br
				FLA (a, b and c)	-2-(3-CF-pyridyl group)	-H	-F
FLB (a, b and c)	-2-(3-CF-pyridyl group)	-H	-CH
				FLC (a, b and c)	-2-(3-CF-pyridyl group)	-H	-CF
FLD (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCH
				FLE (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCHCH
FLF (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCF
				FLG (a, b and c)	-2-(3-CF-pyridyl group)	-H	-tert-butyl
FLH (a, b and c)	-2-(3-CF-pyridyl group)	-H	-isopropyl group
				FLI (a, b and c)	-4- (5-chloropyrimidinyl)	-Cl	-H
FLJ (a, b and c)	-4- (5-chloropyrimidinyl)	-Br	-H
				FLK (a, b and c)	-4- (5-chloropyrimidinyl)	-F	-H
FLL (a, b and c)	-4- (5-chloropyrimidinyl)	-CH	-H

FLM (a, b and c)	-4- (5-chloropyrimidinyl)	-CF	-H
				FLN (a, b and c)	-4- (5-chloropyrimidinyl)	-OCH	-H
FLO (a, b and c)	-4- (5-chloropyrimidinyl)	-OCHCH	-H
				FLP (a, b and c)	-4- (5-chloropyrimidinyl)	-OCF	-H
FLQ (a, b and c)	-4- (5-chloropyrimidinyl)	-tert-butyl	-H
				FLR (a, b and c)	-4- (5-chloropyrimidinyl)	-isopropyl group	-H
FLS (a, b and c)	-4- (5-chloropyrimidinyl)	-CH	-CH
				FLT (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-H
FLU (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-Cl
				FLV (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-Br
FLW (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-F
				FLX (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-CH
FLY (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-CF
				FLZ (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCH
FMA (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCHCH
				FMB (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCF
FMC (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-tert-butyl
				FMD (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-isopropyl group
FME (a, b and c)	-4- (5-methylpyrimidinyl)	-Cl	-H
				FMF (a, b and c)	-4- (5-methylpyrimidinyl)	-Br	-H
FMG (a, b and c)	-4- (5-methylpyrimidinyl)	-F	-H
				FMH (a, b and c)	-4- (5-methylpyrimidinyl)	-CH	-H
FMI (a, b and c)	-4- (5-methylpyrimidinyl)	-CF	-H
				FMJ (a, b and c)	-4- (5-methylpyrimidinyl)	-OCH	-H
FMK (a, b and c)	-4- (5-methylpyrimidinyl)	-OCHCH	-H
				FML (a, b and c)	-4- (5-methylpyrimidinyl)	-OCF	-H
FMM (a, b and c)	-4- (5-methylpyrimidinyl)	-tert-butyl	-H

FMN (a, b and c)	-4- (5-methylpyrimidinyl)	-isopropyl group	-H
				FMO (a, b and c)	-4- (5-methylpyrimidinyl)	-CH	-CH
FMP (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-H
				FMQ (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-Cl
FMR (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-Br
				FMS (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-F
FMT (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-CH
				FMU (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-CF
FMV (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCH
				FMW (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCHCH
FMX (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCF
				FMY (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-tert-butyl
FMZ (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-isopropyl group
				FNA (a, b and c)	-2-pyrazinyl radical	-Cl	-H
FNB (a, b and c)	-2-pyrazinyl radical	-Br	-H
				FNC (a, b and c)	-2-pyrazinyl radical	-F	-H
FND (a, b and c)	-2-pyrazinyl radical	-CH	-H
				FNE (a, b and c)	-2-pyrazinyl radical	-CF	-H
FNF (a, b and c)	-2-pyrazinesBase of	-OCH	-H
				FNG (a, b and c)	-2-pyrazinyl radical	-OCHCH	-H
FNH (a, b and c)	-2-pyrazinyl radical	-OCF	-H
				FNI (a, b and c)	-2-pyrazinyl radical	-tert-butyl	-H
FNJ (a, b and c)	-2-pyrazinyl radical	-isopropyl group	-H
				FNK (a, b and c)	-2-pyrazinyl radical	-CH	-CH
FNL (a, b and c)	-2-pyrazinyl radical	-H	-H
				FNM (a, b and c)	-2-pyrazinyl radical	-H	-Cl
FNN (a, b and c)	-2-pyrazinyl radical	-H	-Br

FNO (a, b and c)	-2-pyrazinyl radical	-H	-F
				FNP (a, b and c)	-2-pyrazinyl radical	-H	-CH
FNQ (a, b and c)	-2-pyrazinyl radical	-H	-CF
				FNR (a, b and c)	-2-pyrazinyl radical	-H	-OCH
FNS (a, b and c)	-2-pyrazinyl radical	-H	-OCHCH
				FNT (a, b and c)	-2-pyrazinyl radical	-H	-OCF
FNU (a, b and c)	-2-pyrazinyl radical	-H	-tert-butyl
				FNV (a, b and c)	-2-pyrazinyl radical	-H	-isopropyl group
FNW (a, b and c)	-2- (3-chloropyrazinyl)	-Cl	-H
				FNX (a, b and c)	-2- (3-chloropyrazinyl)	-Br	-H
FNY (a, b and c)	-2- (3-chloropyrazinyl)	-F	-H
				FNZ (a, b and c)	-2- (3-chloropyrazinyl)	-CH	-H
FOA (a, b and c)	-2- (3-chloropyrazinyl)	-CF	-H
				FOB (a, b and c)	-2- (3-chloropyrazinyl)	-OCH	-H
FOC (a, b and c)	-2- (3-chloropyrazinyl)	-OCHCH	-H
				FOD (a, b and c)	-2- (3-chloropyrazinyl)	-OCF	-H
FOE (a, b and c)	-2- (3-chloropyrazinyl)	-tert-butyl	-H
				FOF (a, b and c)	-2- (3-chloropyrazinyl)	-isopropyl group	-H
FOG (a, b and c)	-2- (3-chloropyrazinyl)	-CH	-CH
				FOH (a, b and c)	-2- (3-chloropyrazinyl)	-H	-H
FOI (a, b and c)	-2- (3-chloropyrazinyl)	-H	-Cl
				FOJ (a, b and c)	-2- (3-chloropyrazinyl)	-H	-Br
FOK (a, b and c)	-2- (3-chloropyrazinyl)	-H	-F
				FOL (a, b and c)	-2- (3-chloropyrazinyl)	-H	-CH
FOM (a, b and c)	-2- (3-chloropyrazinyl)	-H	-CF
				FON (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCH
FOO (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCHCH

FOP (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCF
				FOQ (a, b and c)	-2- (3-chloropyrazinyl)	-H	-tert-butyl
FOR (a, b and c)	-2- (3-chloropyrazinyl)	-H	-isopropyl group
				FOS (a, b and c)	-2- (3-methylpyrazinyl)	-Cl	-H
FOT (a, b and c)	-2- (3-methylpyrazinyl)	-Br	-H
				FOU (a, b and c)	-2- (3-methylpyrazinyl)	-F	-H
FOV (a, b and c)	-2- (3-methylpyrazinyl)	-CH	-H
				FOW (a, b and c)	-2- (3-methylpyrazinyl)	-CF	-H
FOX (a, b and c)	-2- (3-methylpyrazinyl)	-OCH	-H
				FOY (a, b and c)	-2- (3-methylpyrazinyl)	-OCHCH	-H
FOZ (a, b and c)	-2- (3-methylpyrazinyl)	-OCF	-H
				FPA (a, b and c)	-2- (3-methylpyrazinyl)	-tert-butyl	-H
FPB (a, b and c)	-2- (3-methylpyrazinyl)	-isopropyl group	-H
				FPC (a, b and c)	-2- (3-methylpyrazinyl)	-CH	-CH
FPD (a, b and c)	-2- (3-methylpyrazinyl)	-H	-H
				FPE (a, b and c)	-2- (3-methylpyrazinyl)	-H	-Cl
FPF (a, b and c)	-2- (3-methylpyrazinyl)	-H	-Br
				FPG (a, b and c)	-2- (3-methylpyrazinyl)	-H	-F
FPH (a, b and c)	-2- (3-methylpyrazinyl)	-H	-CH
				FPI (a, b and c)	-2- (3-methylpyrazinyl)	-H	-CF
FPJ (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCH
				FPK (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCHCH
FPL (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCF
				FPM (a, b and c)	-2- (3-methylpyrazinyl)	-H	-tert-butyl
FPN (a, b and c)	-2- (3-methylpyrazinyl)	-H	-isopropyl group
				FPO (a, b and c)	-2-pyridazinyl radical	-Cl	-H
FPP (a, b and c)	-2-pyridazinyl radical	-Br	-H

FPQ (a, b and c)	-2-pyridazinyl radical	-F	-H
				FPR (a, b and c)	-2-pyridazinyl radical	-CH	-H
FPS (a, b and c)	-2-pyridazinyl radical	-CF	-H
				FPT (a, b and c)	-2-pyridazinyl radical	-OCH	-H
FPU (a, b and c)	-2-pyridazinyl radical	-OCHCH	-H
				FPV (a, b and c)	-2-pyridazinyl radical	-OCF	-H
FPW (a, b and c)	-2-pyridazinyl radical	-tert-butyl	-H
				FPX (a, b and c)	-2-pyridazinyl radical	-isopropyl group	-H
FPY (a, b and c)	-2-pyridazinyl radical	-CH	-CH
				FPZ (a, b and c)	-2-pyridazinyl radical	-H	-H
FQA (a, b and c)	-2-pyridazinyl radical	-H	-Cl
				FQB (a, b and c)	-2-pyridazinyl radical	-H	-Br
FQC (a, b and c)	-2-pyridazinyl radical	-H	-F
				FQD (a, b and c)	-2-pyridazinyl radical	-H	-CH
FQE (a, b and c)	-2-pyridazinyl radical	-H	-CF
				FQF (a, b and c)	-2-pyridazinyl radical	-H	-OCH
FQG (a, b and c)	-2-pyridazinyl radical	-H	-OCHCH
				FQH (a, b and c)	-2-pyridazinyl radical	-H	-OCF
FQI (a, b and c)	-2-pyridazinyl radical	-H	-tert-butyl
				FQJ (a, b and c)	-2-pyridazinyl radical	-H	-isopropyl group
FQK (a, b and c)	-3- (4-chloropyridazinyl)	-Cl	-H
				FQL (a, b and c)	-3- (4-chloropyridazinyl)	-Br	-H
FQM (a, b and c)	-3- (4-chloropyridazinyl)	-F	-H
				FQN (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-H
FQO (a, b and c)	-3- (4-chloropyridazinyl)	-CF	-H
				FQP (a, b and c)	-3- (4-chloropyridazinyl)	-OCH	-H
FQQ (a, b and c)	-3- (4-chloropyridazinyl)	-OCHCH	-H

FQR (a, b and c)	-3- (4-chloropyridazinyl)	-OCF	-H
				FQS (a, b and c)	-3- (4-chloropyridazinyl)	-tert-butyl	-H
FQT (a, b and c)	-3- (4-chloropyridazinyl)	-isopropyl group	-H
				FQU (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-CH
FQV (a, b and c)	-3- (4-chloropyridazinyl)	-H	-H
				FQW (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Cl
FQX (a, b and c))	-3- (4-chloropyridazinyl)	-H	-Br
				FQY (a, b and c)	-3- (4-chloropyridazinyl)	-H	-F
FQZ (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CH
				FRA (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CF
FRB (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCH
				FRC (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCHCH
FRD (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCF
				FRE (a, b and c)	-3- (4-chloropyridazinyl)	-H	-tert-butyl
FRF (a, b and c)	-3- (4-chloropyridazinyl)	-H	-isopropyl group
				FRG (a, b and c)	-3- (4-methylpyridazinyl)	-Cl	-H
FRH (a, b and c)	-3- (4-methylpyridazinyl)	-Br	-H
				FRI (a, b and c)	-3- (4-methylpyridazinyl)	-F	-H
FRJ (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-H
				FRK (a, b and c)	-3- (4-methylpyridazinyl)	-CF	-H
FRL (a, b and c)	-3- (4-methylpyridazinyl)	-OCH	-H
				FRM (a, b and c)	-3- (4-methylpyridazinyl)	-OCHCH	-H
FRN (a, b and c)	-3- (4-methylpyridazinyl)	-OCF	-H
				FRO (a, b and c)	-3- (4-methylpyridazinyl)	-tert-butyl	-H
FRP (a, b and c)	-3- (4-methylpyridazinyl)	-isopropyl group	-H
				FRQ (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-CH
FRR (a, b and c)	-3- (4-methylpyridazinyl)	-H	-H

FRS (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Cl
				FRT (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Br
FRU (a, b and c)	-3- (4-methylpyridazinyl)	-H	-F
				FRV (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CH
FRW (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CF
				FRX (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCH
FRY (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCHCH
				FRZ (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCF
FSA (a, b and c)	-3- (4-methylpyridazinyl)	-H	-tert-butyl
				FSB (a, b and c)	-3- (4-methylpyridazinyl)	-H	-isopropyl group
FSC (a, b and c)	-4-thiazanyl	-Cl	-H
				FSD (a, b and c)	-4-thiazanyl	-Br	-H
FSE (a, b and c)	-4-thiazanyl	-F	-H
				FSF (a, b and c)	-4-thiazanyl	-CH	-H
FSG (a, b and c)	-4-thiazanyl	-CF	-H
				FSH (a, b and c)	-4-thiazanyl	-OCH	-H
FSI (a, b and c)	-4-thiazanyl	-OCHCH	-H
				FSJ (a, b and c)	-4-thiazanyl	-OCF	-H
FSK (a, b and c)	-4-thiazanyl	-tert-butyl	-H
				FSL (a, b and c)	-4-thiazanyl	-isopropyl group	-H
FSM (a, b and c)	-4-thiazanyl	-CH	-CH
				FSN (a, b and c)	-4-thiazanyl	-H	-H
FSO (a, b and c)	-4-thiazanyl	-H	-Cl
				FSP (a, b and c)	-4-thiazanyl	-H	-Br
FSQ (a, b and c)	-4-thiazanyl	-H	-F
				FSR (a, b and c)	-4-thiazanyl	-H	-CH
FSS (a, b and c)	-4-thiazanyl	-H	-CF

FST (a, b and c)	-4-thiazanyl	-H	-OCH
				FSU (a, b and c)	-4-thiazanyl	-H	-OCHCH
FSV (a, b and c)	-4-thiazanyl	-H	-OCF
				FSW (a, b and c)	-4-thiazanyl	-H	-tert-butyl
FSX (a, b and c)	-4-thiazanyl	-H	-isopropyl group
				FSY (a, b and c)	-5- (4-chloro-thiazanyl)	-Cl	-H
FSZ (a, b and c)	-5- (4-chloro-thiazanyl)	-Br	-H
				FTA (a, b and c)	-5- (4-chloro-thiazanyl)	-F	-H
FTB (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-H
				FTC (a, b and c)	-5- (4-chloro-thiazanyl)	-CF	-H
FTD (a, b and c)	-5- (4-chloro-thiazanyl)	-OCH	-H
				FTE (a, b and c)	-5- (4-chloro-thiazanyl)	-OCHCH	-H
FTF (a, b and c)	-5- (4-chloro-thiazanyl)	-OCF	-H
				FTG (a, b and c)	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
FTH (a, b and c)	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
				FTI (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-CH
FTJ (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-H
				FTK (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Cl
FTL (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Br
				FTM (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-F
FTN (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CH
				FTO (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CF
FTP (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCH
				FTQ (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCHCH
FTR (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCF
				FTS (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
FTT (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-isopropyl group

FTU (a, b and c)	-5- (4-methylthiozanyl)	-Cl	-H
				FTV (a, b and c)	-5- (4-methylthiozanyl)	-Br	-H
FTW (a, b and c)	-5- (4-methylthiozanyl)	-F	-H
				FTX (a, b and c)	-5- (4-methyl thiazanyl)	-CH	-H
FTY (a, b and c)	-5- (4-methylthiozanyl)	-CF	-H
				FTZ (a, b and c)	-5- (4-methylthiozanyl)	-OCH	-H
FUA (a, b and c)	-5- (4-methylthiozanyl)	-OCHCH	-H
				FUB (a, b and c)	-5- (4-methylthiozanyl)	-OCF	-H
FUC (a, b and c)	-5- (4-methylthiozanyl)	-tert-butyl	-H
				FUD (a, b and c)	-5- (4-methylthiozanyl)	-isopropyl group	-H
FUE (a, b and c)	-5- (4-methylthiozanyl)	-CH	-CH
				FUF (a, b and c)	-5- (4-methylthiozanyl)	-H	-H
FUG (a, b and c)	-5- (4-methylthiozanyl)	-H	-Cl
				FUH (a, b and c)	-5- (4-methylthiozanyl)	-H	-Br
FUI (a, b and c)	-5- (4-methylthiozanyl)	-H	-F
				FUJ (a, b and c)	-5- (4-methylthiozanyl)	-H	-CH
FUK (a, b and c)	-5- (4-methylthiozanyl)	-H	-CF
				FUL (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCH
FUM (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCHCH
				FUN (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCF
FUO (a, b and c)	-5- (4-methylthiozanyl)	-H	-tert-butyl
				FUP (a, b and c)	-5- (4-methylthiozanyl)	-H	-isopropyl group

"a" indicates that the benzoxazole piperazine compound is racemic.

"b" indicates that the carbon atom of the piperazine ring to which the methyl group is attached is in the R configuration.

"c" indicates that the carbon atom of the piperazine ring to which the methyl group is attached is in the S configuration.

TABLE XVI

And pharmaceutically acceptable salts thereof, wherein:

Compound (I)	Ar	R	R
				FUQ (a, b and c)	-2- (3-chloropyridyl)	-Cl	-H
FUR (a, b and c)	-2- (3-chloropyridyl)	-Br	-H
				FUS (a, b and c)	-2- (3-chloropyridyl)	-F	-H
FUT (a, b and c)	-2- (3-chloropyridyl)	-CH	-H
				FUU (a, b and c)	-2- (3-chloropyridyl)	-CF	-H
FUV (a, b and c)	-2- (3-chloropyridyl)	-OCH	-H
				FUW (a, b and c)	-2- (3-chloropyridyl)	-OCHCH	-H
FUX (a, b and c)	-2- (3-chloropyridyl)	-OCF	-H
				FUY (a, b and c)	-2- (3-chloropyridyl)	-tert-butyl	-H
FUZ (a, b and c)	-2- (3-chloropyridyl)	-isopropyl group	-H
				FVA (a, b and c)	-2- (3-chloropyridyl)	-CH	-CH
FVB (a, b and c)	-2- (3-chloropyridyl)	-H	-H
				FVC (a, b and c)	-2- (3-chloropyridyl)	-H	-Cl
FVD (a, b and c)	-2- (3-chloropyridyl)	-H	-Br
				FVE (a, b and c)	-2- (3-chloropyridyl)	-H	-F
FVF (a, b and c)	-2- (3-chloropyridyl)	-H	-CH

FVG (a, b and c)	-2- (3-chloropyridyl)	-H	-CF
				FVH (a, b and c)	-2- (3-chloropyridyl)	-H	-OCH
FVI (a, b and c)	-2- (3-chloropyridyl)	-H	-OCHCH
				FVJ (a, b and c)	-2- (3-chloropyridyl)	-H	-OCF
FVK (a, b and c)	-2- (3-chloropyridyl)	-H	-tert-butyl
				FVL (a, b and c)	-2- (3-chloropyridyl)	-H	-isopropyl group
FVM (a, b and c)	-2- (3-methylpyridinyl)	-Cl	-H
				FVN (a, b and c)	-2- (3-methylpyridinyl)	-Br	-H
FVO (a, b and c)	-2- (3-methylpyridinyl)	-F	-H
				FVP (a, b and c)	-2- (3-methylpyridinyl)	-CH	-H
FVQ (a, b and c)	-2- (3-methylpyridinyl)	-CF	-H
				FVR (a, b and c)	-2- (3-methylpyridinyl)	-OCH	-H
FVS (a, b and c)	-2- (3-methylpyridinyl)	-OCHCH	-H
				FVT (a, b and c)	-2- (3-methylpyridinyl)	-OCF	-H
FVU (a, b and c)	-2- (3-methylpyridinyl)	-tert-butyl	-H
				FVV (a, b and c)	-2- (3-methylpyridinyl)	-isopropyl group	-H
FVW (a, b and c)	-2- (3-methylpyridinyl)	-CH	-CH
				FVX (a, b and c)	-2- (3-methylpyridinyl)	-H	-H
FVY (a, b and c)	-2- (3-methylpyridinyl)	-H	-Cl
				FVZ (a, b and c)	-2- (3-methylpyridinyl)	-H	-Br
FWA (a, b and c)	-2- (3-methylpyridinyl)	-H	-F
				FWB (a, b and c)	-2- (3-methylpyridinyl)	-H	-CH
FWC (a, b and c)	-2- (3-methylpyridinyl)	-H	-CF
				FWD (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCH
FWE (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCHCH
				FWF (a, b and c)	-2- (3-methylpyridinyl)	-H	-OCF
FWG (a, b and c)	-2- (3-methylpyridinyl)	-H	-tert-butyl

FWH (a, b and c)	-2- (3-methylpyridinyl)	-H	-isopropyl group
				FWI (a, b and c)	-2-(3-CF-pyridyl group)	-Cl	-H
FWJ (a, b and c)	-2-(3-CF-pyridyl group)	-Br	-H
				FWK (a, b and c)	-2-(3-CF-pyridyl group)	-F	-H
FWL (a, b and c)	-2-(3-CF-pyridyl group)	-CH	-H
				FWM (a, b and c)	-2-(3-CF-pyridyl group)	-CF	-H
FWN (a, b and c)	-2-(3-CF-pyridyl group)	OCH	-H
				FWO (a, b and c)	-2-(3-CF-pyridyl group)	-OCHCH	-H
FWP (a, b and c)	-2- (3-CF-3 pyridyl)	-OCF	-H
				FWQ (a, b and c)	-2-(3-CF-pyridyl group)	-tert-butyl	-H
FWR (a, b and c)	-2-(3-CF-pyridyl group)	-isopropyl group	-H
				FWS (a, b and c)	-2-(3-CF-pyridyl group)	-CH	-CH
FWT (a, b and c)	-2-(3-CF-pyridyl group)	-H	-H
				FWU (a, b and c)	-2-(3-CF-pyridyl group)	-H	-Cl
FWV (a, b and c)	-2-(3-CF-pyridyl group)	-H	-Br
				FWW (a, b and c)	-2-(3-CF-pyridyl group)	-H	-F
FWX (a, b and c)	-2-(3-CF-pyridyl group)	-H	-CH
				FWY (a, b and c)	-2-(3-CF-pyridyl group)	-H	-CF
FWZ (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCH
				FXA (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCHCH
FXB (a, b and c)	-2-(3-CF-pyridyl group)	-H	-OCF
				FXC (a, b and c)	-2-(3-CF-pyridyl group)	-H	-tert-butyl
FXD (a, b and c)	-2-(3-CF-pyridyl group)	-H	-isopropyl group
				FXE (a, b and c)	-4- (5-chloropyrimidinyl)	-Cl	-H
FXF (a, b and c)	-4- (5-chloropyrimidinyl)	-Br	-H
				FXG (a, b and c)	-4- (5-chloropyrimidinyl)	-F	-H
FXH (a, b and c)	-4- (5-chloropyrimidinyl)	-CH	-H

FXI (a, b and c)	-4- (5-chloropyrimidinyl)	-CF	-H
				FXJ (a, b and c)	-4- (5-chloropyrimidinyl)	-OCH	-H
FXK (a, b and c)	-4- (5-chloropyrimidinyl)	-OCHCH	-H
				FXL (a, b and c)	-4- (5-chloropyrimidinyl)	-OCF	-H
FXM (a, b and c)	-4- (5-chloropyrimidinyl)	-tert-butyl	-H
				FXN (a, b and c)	-4- (5-chloropyrimidinyl)	-isopropyl group	-H
FXO (a, b and c)	-4- (5-chloropyrimidinyl)	-CH	-CH
				FXP (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-H
FXQ (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-Cl
				FXR (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-Br
FXS (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-F
				FXT (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-CH
FXU (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-CF
				FXV (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCH
FXW (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCHCH
				FXX (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-OCF
FXY (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-tert-butyl
				FXZ (a, b and c)	-4- (5-chloropyrimidinyl)	-H	-isopropyl group
FYA (a, b and c)	-4- (5-methylpyrimidinyl)	-Cl	-H
				FYB (a, b and c)	-4- (5-methylpyrimidinyl)	-Br	-H
FYC (a, b and c)	-4- (5-methylpyrimidinyl)	-F	-H
				FYD (a, b and c)	-4- (5-methylpyrimidinyl)	-CH	-H
FYE (a, b and c)	-4- (5-methylpyrimidinyl)	-CF	-H
				FYF (a, b and c)	-4- (5-methylpyrimidinyl)	-OCH	-H
FYG (a, b and c)	-4- (5-methylpyrimidinyl)	-OCHCH	-H
				FYH (a, b and c)	-4- (5-methylpyrimidinyl)	-OCF	-H
FYI (a, b and c)	-4- (5-methyl)Pyrimidinyl)	-tert-butyl	-H

FYJ (a, b and c)	-4- (5-methylpyrimidinyl)	-isopropyl group	-H
				FYK (a, b and c)	-4- (5-methylpyrimidinyl)	-CH	-CH
FYL (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-H
				FYM (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-Cl
FYN (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-Br
				FYO (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-F
FYP (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-CH
				FYQ (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-CF
FYR (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCH
				FYS (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-OCHCH
FYT (a, b and c)	-4- (5-methylpyrimidine)Pyridyl radical)	-H	-OCF
				FYU (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-tert-butyl
FYV (a, b and c)	-4- (5-methylpyrimidinyl)	-H	-isopropyl group
				FYW (a, b and c)	-2-pyrazinyl radical	-Cl	-H
FYX (a, b and c)	-2-pyrazinyl radical	-Br	-H
				FYY (a, b and c)	-2-pyrazinyl radical	-F	-H
FYZ (a, b and c)	-2-pyrazinyl radical	-CH	-H
				FZA (a, b and c)	-2-pyrazinyl radical	-CF	-H
FZB (a, b and c)	-2-pyrazinyl radical	-OCH	-H
				FZC (a, b and c)	-2-pyrazinyl radical	-OCHCH	-H
FZD (a, b and c)	-2-pyrazinyl radical	-OCF	-H
				FZE (a, b and c)	-2-pyrazinyl radical	-tert-butyl	-H
FZF (a, b and c)	-2-pyrazinyl radical	-isopropyl group	-H
				FZG (a, b and c)	-2-pyrazinyl radical	-CH	-CH
FZH (a, b and c)	-2-pyrazinyl radical	-H	-H
				FZI (a, b and c)	-2-pyrazinyl radical	-H	-Cl
FZJ (a, b and c)	-2-pyrazinyl radical	-H	-Br

FZK (a, b and c)	-2-pyrazinyl radical	-H	-F
				FZL (a, b and c)	-2-pyrazinesBase of	-H	-CH
FZM (a, b and c)	-2-pyrazinyl radical	-H	-CF
				FZN (a, b and c)	-2-pyrazinyl radical	-H	-OCH
FZO (a, b and c)	-2-pyrazinyl radical	-H	-OCHCH
				FZP (a, b and c)	-2-pyrazinyl radical	-H	-OCF
FZQ (a, b and c)	-2-pyrazinyl radical	-H	-tert-butyl
				FZR (a, b and c)	-2-pyrazinyl radical	-H	-isoPropyl radical
FZS (a, b and c)	-2- (3-chloropyrazinyl)	-Cl	-H
				FZT (a, b and c)	-2- (3-chloropyrazinyl)	-Br	-H
FZU (a, b and c)	-2- (3-chloropyrazinyl)	-F	-H
				FZV (a, b and c)	-2- (3-chloropyrazinyl)	-CH	-H
FZW (a, b and c)	-2- (3-chloropyrazinyl)	-CF	-H
				FZX (a, b and c)	-2- (3-chloropyrazinyl)	-OCH	-H
FZY (a, b and c)	-2- (3-chloropyrazinyl)	-OCHCH	-H
				FZZ (a, b and c)	-2- (3-chloropyrazinyl)	-OCF	-H
GAA (a, b and c)	-2- (3-chloropyrazinyl)	-tert-butyl	-H
				GAB (a, b and c)	-2- (3-chloropyrazinyl)	-isopropyl group	-H
GAC (a, b and c)	-2- (3-chloropyrazinyl)	-CH	-CH
				GAD (a, b and c)	-2- (3-chloropyrazinyl)	-H	-H
GAE (a, b and c)	-2- (3-chloropyrazinyl)	-H	-Cl
				GAF (a, b and c)	-2- (3-chloropyrazinyl)	-H	-Br
GAG (a, b and c)	-2- (3-chloropyrazinyl)	-H	-F
				GAH (a, b and c)	-2- (3-chloropyrazinyl)	-H	-CH
GAI (a, b and c)	-2- (3-chloropyrazinyl)	-H	-CF
				GAJ (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCH
GAK (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCHCH

GAL (a, b and c)	-2- (3-chloropyrazinyl)	-H	-OCF
				GAM (a, b and c)	-2- (3-chloropyrazinyl)	-H	-tert-butyl
GAN (a, b and c)	-2- (3-chloropyrazinyl)	-H	-isopropyl group
				GAO (a, b and c)	-2- (3-methylpyrazinyl)	-Cl	-H
GAP (a, b and c)	-2- (3-methylpyrazinyl)	-Br	-H
				GAQ (a, b and c)	-2- (3-methylpyrazinyl)	-F	-H
GAR (a, b and c)	-2- (3-methylpyrazinyl)	-CH	-H
				GAS (a, b and c)	-2- (3-methylpyrazinyl)	-CF	-H
GAT (a, b and c)	-2- (3-methylpyrazinyl)	-OCH	-H
				GAU (a, b and c)	-2- (3-methylpyrazinyl)	-OCHCH	-H
GAV (a, b and c)	-2- (3-methylpyrazinyl)	-OCF	-H
				GAW (a, b and c)	-2- (3-methylpyrazinyl)	-tert-butyl	-H
GAX (a, b and c)	-2- (3-methylpyrazinyl)	-isopropyl group	-H
				GAY (a, b and c)	-2- (3-methylpyrazinyl)	-CH	-CH
GAZ (a, b and c)	-2- (3-methylpyrazinyl)	-H	-H
				GBA (a, b and c)	-2- (3-methylpyrazinyl)	-H	-Cl
GBB (a, b and c)	-2- (3-methylpyrazinyl)	-H	-Br
				GBC (a, b and c)	-2- (3-methylpyrazinyl)	-H	-F
GBD (a, b and c)	-2- (3-methylpyrazinyl)	-H	-CH
				GBE (a, b and c)	-2- (3-methylpyrazinyl)	-H	-CF
GBF (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCH
				GBG (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCHCH
GBH (a, b and c)	-2- (3-methylpyrazinyl)	-H	-OCF
				GBI (a, b and c)	-2- (3-methylpyrazinyl)	-H	-tert-butyl
GBJ (a, b and c)	-2- (3-methylpyrazinyl)	-H	-isopropyl group
				GBK (a, b and c)	-2-pyridazinyl radical	-Cl	-H
GBL (a, b and c)	-2-pyridazinyl radical	-Br	-H

GBM (a, b and c)	-2-pyridazinyl radical	-F	-H
				GBN (a, b and c)	-2-pyridazinyl radical	-CH	-H
GBO (a, b and c)	-2-pyridazinyl radical	-CF	-H
				GBP (a, b and c)	-2-pyridazinyl radical	-OCH	-H
GBQ (a, b and c)	-2-pyridazinyl radical	-OCHCH	-H
				GBR (a, b and c)	-2-pyridazinyl radical	-OCF	-H
GBS (a, b and c)	-2-pyridazinyl radical	-tert-butyl	-H
				GBT (a, b and c)	-2-pyridazinyl radical	-isopropyl group	-H
GBU (a, b and c)	-2-pyridazinyl radical	-CH	-CH
				GBV (a, b and c)	-2-pyridazinyl radical	-H	-H
GBW (a, b and c)	-2-pyridazinyl radical	-H	-Cl
				GBX (a, b and c)	-2-pyridazinyl radical	-H	-Br
GBY (a, b and c)	-2-pyridazinyl radical	-H	-F
				GBZ (a, b and c)	-2-pyridazinyl radical	-H	-CH
GCA (a, b and c)	-2-pyridazinyl radical	-H	-CF
				GCB (a, b and c)	-2-pyridazinyl radical	-H	-OCH
GCC (a, b and c)	-2-pyridazinyl radical	-H	-OCHCH
				GCD (a, b and c)	-2-pyridazinyl radical	-H	-OCF
GCE (a, b and c)	-2-pyridazinyl radical	-H	-tert-butyl
				GCF (a, b and c)	-2-pyridazinyl radical	-H	-isopropyl group
GCG (a, b and c)	-3- (4-chloropyridazinyl)	-Cl	-H
				GCH (a, b and c)	-3- (4-chloropyridazinyl)	-Br	-H
GCI (a, b and c)	-3- (4-chloropyridazinyl)	-F	-H
				GCJ (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-H
GCK (a, b and c)	-3- (4-chloropyridazinyl)	-CF	-H
				GCL (a, b and c)	-3- (4-chloropyridazinyl)	-OCH	-H
GCM (a, b and c)	-3- (4-chloropyridazinyl)	-OCHCH	-H

GCN (a, b and c)	-3- (4-chloropyridazinyl)	-OCF	-H
				GCO (a, b and c)	-3- (4-chloropyridazinyl)	-tert-butyl	-H
GCP (a, b and c)	-3- (4-chloropyridazinyl)	-isopropyl group	-H
				GCQ (a, b and c)	-3- (4-chloropyridazinyl)	-CH	-CH
GCR (a, b and c)	-3- (4-chloropyridazinyl)	-H	-H
				GCS (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Cl
GCT (a, b and c)	-3- (4-chloropyridazinyl)	-H	-Br
				GCU (a, b and c)	-3- (4-chloropyridazinyl)	-H	-F
GCV (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CH
				GCW (a, b and c)	-3- (4-chloropyridazinyl)	-H	-CF
GCX (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCH
				GCY (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCHCH
GCZ (a, b and c)	-3- (4-chloropyridazinyl)	-H	-OCF
				GDA (a, b and c)	-3- (4-chloropyridazinyl)	-H	-tert-butyl
GDB (a, b and c)	-3- (4-chloropyridazinyl)	-H	-isopropyl group
				GDC (a, b and c)	-3- (4-methylpyridazinyl)	-Cl	-H
GDD (a, b and c)	-3- (4-methylpyridazinyl)	-Br	-H
				GDE (a, b and c)	-3- (4-methylpyridazinyl)	-F	-H
GDF (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-H
				GDG (a, b and c)	-3- (4-methylpyridazinyl)	-CF	-H
GDH (a, b and c)	-3- (4-methylpyridazinyl)	-OCH	-H
				GDI (a, b and c)	-3- (4-methylpyridazinyl)	-OCHCH	-H
GDJ (a, b and c)	-3- (4-methylpyridazinyl)	-OCF	-H
				GDK (a, b and c)	-3- (4-methylpyridazinyl)	-tert-butyl	-H
GDL (a, b and c)	-3- (4-methylpyridazinyl)	-isopropyl group	-H
				GDM (a, b and c)	-3- (4-methylpyridazinyl)	-CH	-CH
GDN (a, b and c)	-3- (4-methylpyridazinyl)	-H	-H

GDO (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Cl
				GDP (a, b and c)	-3- (4-methylpyridazinyl)	-H	-Br
GDQ (a, b and c)	-3- (4-methylpyridazinyl)	-H	-F
				GDR (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CH
GDS (a, b and c)	-3- (4-methylpyridazinyl)	-H	-CF
				GDT (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCH
GDU (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCHCH
				GDV (a, b and c)	-3- (4-methylpyridazinyl)	-H	-OCF
GDW (a, b and c)	-3- (4-methylpyridazinyl)	-H	-tert-butyl
				GDX (a, b and c)	-3- (4-methylpyridazinyl)	-H	-isopropyl group
GDY (a, b and c)	-4-thiazanyl	-Cl	-H
				GDZ (a, b and c)	-4-thiazanyl	-Br	-H
GEA (a, b and c)	-4-thiazanyl	-F	-H
				GEB (a, b and c)	-4-thiazanyl	-CH	-H
GEC (a, b and c)	-4-thiazanyl	-CF	-H
				GED (a, b and c)	-4-thiazanyl	-OCH	-H
GEE (a, b and c)	-4-thiazanyl	-OCHCH	-H
				GEF (a, b and c)	-4-thiazanyl	-OCF	-H
GEG (a, b and c)	-4-thiazanyl	-tert-butyl	-H
				GEH (a, b and c)	-4-thiazanyl	-isopropyl group	-H
GEI (a, b and c)	-4-thiazanyl	-CH	-CH
				GEJ (a, b and c)	-4-thiazanyl	-H	-H
GEK (a, b and c)	-4-thiazanyl	-H	-Cl
				GEL (a, b and c)	-4-thiazanyl	-H	-Br
GEM (a, b and c)	-4-thiazanyl	-H	-F
				GEN (a, b and c)	-4-thiazanyl	-H	-CH
GEO (a, b and c)	-4-thiazanyl	-H	-CF

GEP (a, b and c)	-4-thiazanyl	-H	-OCH
				GEQ (a, b and c)	-4-thiazanyl	-H	-OCHCH
GER (a, b and c)	-4-thiazanyl	-H	-OCF
				GES (a, b and c)	-4-thiazanyl	-H	-tert-butyl
GET (a, b and c)	-4-thiazanyl	-H	-isopropyl group
				GEU (a, b and c)	-5- (4-chloro-thiazanyl)	-Cl	-H
GEV (a, b and c)	-5- (4-chloro-thiazanyl)	-Br	-H
				GEW (a, b and c)	-5- (4-chloro-thiazanyl)	-F	-H
GEX (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-H
				GEY (a, b and c)	-5- (4-chloro-thiazanyl)	-CF	-H
GEZ (a, b and c)	-5- (4-chloro-thiazanyl)	-OCH	-H
				GFA (a, b and c)	-5- (4-chloro-thiazanyl)	-OCHCH	-H
GFB (a, b and c)	-5- (4-chloro-thiazanyl)	-OCF	-H
				GFC (a, b and c)	-5- (4-chloro-thiazanyl)	-tert-butyl	-H
GFD (a, b and c)	-5- (4-chloro-thiazanyl)	-isopropyl group	-H
				GFE (a, b and c)	-5- (4-chloro-thiazanyl)	-CH	-CH
GFF (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-H
				GFG (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Cl
GFH (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-Br
				GFI (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-F
GFJ (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CH
				GFK (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-CF
GFL (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCH
				GFM (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCHCH
GFN (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-OCF
				GFO (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-tert-butyl
GFP (a, b and c)	-5- (4-chloro-thiazanyl)	-H	-isopropyl group

GFQ (a, b and c)	-5- (4-methylthiozanyl)	-Cl	-H
				GFR (a, b and c)	-5- (4-methylthiozanyl)	-Br	-H
GFS (a, b and c)	-5- (4-methylthiozanyl)	-F	-H
				GFT (a, b and c)	-5- (4-methylthiozanyl)	-CH	-H
GFU (a, b and c)	-5- (4-methylthiozanyl)	-CF	-H
				GFV (a, b and c)	-5- (4-methylthiozanyl)	-OCH	-H
GFW (a, b and c)	-5- (4-methylthiozanyl)	-OCHCH	-H
				GFX (a, b and c)	-5- (4-methylthiozanyl)	-OCF	-H
GFY (a, b and c)	-5- (4-methylthiozanyl)	-tert-butyl	-H
				GFZ (a, b and c)	-5- (4-methylthiozanyl)	-isopropyl group	-H
GGA (a, b and c)	-5- (4-methylthiozanyl)	-CH	-CH
				GGB (a, b and c)	-5- (4-methylthiozanyl)	-H	-H
GGC (a, b and c)	-5- (4-methylthiozanyl)	-H	-Cl
				GGD (a, b and c)	-5- (4-methylthiozanyl)	-H	-Br
GGE (a, b and c)	-5- (4-methylthiozanyl)	-H	-F
				GGF (a, b and c)	-5- (4-methylthiozanyl)	-H	-CH
GGG (a, b and c)	-5- (4-methylthiozanyl)	-H	-CF
				GGH (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCH
GGI (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCHCH
				GGJ (a, b and c)	-5- (4-methylthiozanyl)	-H	-OCF
GGK (a, b and c)	-5- (4-methylthiozanyl)	-H	-tert-butyl
				GGL (a, b and c)	-5- (4-methylthiozanyl)	-H	-isopropyl group

"a" indicates that the benzoxazole piperazine compound is racemic.

"b" indicates that the carbon atom of the piperazine ring to which the methyl group is attached is in the R configuration.

"c" indicates that the carbon atom of the piperazine ring to which the methyl group is attached is in the S configuration.

TABLE XIX

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	X	R	R
				GGM	S	-Cl	-H
GGN	S	-Br	-H
				GGO	S	-F	-H
GGP	S	-CH	-H
				GGQ	S	-CF	-H
GGR	S	-OCH	-H
				GGS	S	-OCHCH	-H
GGT	S	-OCF	-H
				GGU	S	-tert-butyl	-H
GGV	S	-isopropyl group	-H
				GGW	S	-CH	-CH
GGX	S	-H	-H
				GGY	S	-H	-Cl
GGZ	S	-H	-Br
				GHA	S	-H	-F
GHB	S	-H	-CH

GHC	S	-H	-CF
				GHD	S	-H	-OCH
GHE	S	-H	-OCHCH
				GHF	S	-H	-OCF
GHG	S	-H	-tert-butyl
				GHH	S	-H	-isopropyl group
GHI	O	-Cl	-H
				GHJ	O	-Br	-H
GHK	O	-F	-H
				GHL	O	-CH	-H
GHM	O	-CF	-H
				GHN	O	-OCH	-H
GHO	O	-OCHCH	-H
				GHP	O	-OCF	-H
GHQ	O	-tert-butyl	-H
				GHR	O	-isopropyl group	-H
GHS	O	-CH	-CH
				GHT	O	-H	-H
GHU	O	-H	-Cl
				GHV	O	-H	-Br
GHW	O	-H	-F
				GHX	O	-H	-CH
GHY	O	-H	-CF
				GHZ	O	-H	-OCH
GIA	O	-H	-OCHCH
				GIB	O	-H	-OCF
GIC	O	-H	-tert-butyl
				GID	O	-H	-isopropyl group
GIE	N	-Cl	-H
				GIF	N	-Br	-H

GIG	N	-F	-H
				GIH	N	-CH	-H
GII	N	-CF	-H
				GIJ	N	-OCH	-H
GIK	N	-OCHCH	-H
				GIL	N	-OCF	-H
GIM	N	-tert-butyl	-H
				GIN	N	-isopropyl group	-H
GIO	N	-CH	-CH
				GIP	N	-H	-H
GIQ	N	-H	-Cl
				GIR	N	-H	-Br
GIS	N	-H	-F
				GIT	N	-H	-CH
GIU	N	-H	-CF
				GIV	N	-H	-OCH
GIW	N	-H	-OCHCH
				GIX	N	-H	-OCF
GIY	N	-H	-tert-butyl
				GIZ	N	-H	-isopropyl group

Table XX

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	X	R	R
				GJA	S	-Cl	-H
GJB	S	-Br	-H
				GJC	S	-F	-H
GJD	S	-CH	-H
				GJE	S	-CF	-H
GJF	S	-OCH	-H
				GJG	S	-OCHCH	-H
GJH	S	-OCF	-H
				GJI	S	-tert-butyl	-H
GJJ	S	-isopropyl group	-H
				GJK	S	-CH	-CH
GJL	S	-H	-H
				GJM	S	-H	-Cl
GJN	S	-H	-Br
				GJO	S	-H	-F
GJP	S	-H	-CH

GJQ	S	-H	-CF
				GJR	S	-H	-OCH
GJS	S	-H	-OCHCH
				GJT	S	-H	-OCF
GJU	S	-H	-tert-butyl
				GJV	S	-H	-isopropyl group
GJW	O	-Cl	-H
				GJX	O	-Br	-H
GJY	O	-F	-H
				GJZ	O	-CH	-H
GKA	O	-CF	-H
				GKB	O	-OCH	-H
GKC	O	-OCHCH	-H
				GKD	O	-OCF	-H
GKE	O	-tert-butyl	-H
				GKF	O	-isopropyl group	-H
GKG	O	-CH	-CH
				GKH	O	-H	-H
GKI	O	-H	-Cl
				GKJ	O	-H	-Br
GKK	O	-H	-F
				GKL	O	-H	-CH
GKM	O	-H	-CF
				GKN	O	-H	-OCH
GKO	O	-H	-OCHCH
				GKP	O	-H	-OCF
GKQ	O	-H	-tert-butyl
				GKR	O	-H	-isopropyl group
GKS	N	-Cl	-H
				GKT	N	-Br	-H

GKU	N	-F	-H
				GKV	N	-CH	-H
GKW	N	-CF	-H
				GKX	N	-OCH	-H
GKY	N	-OCHCH	-H
				GKZ	N	-OCF	-H
GLA	N	-tert-butyl	-H
				GLB	N	-isopropyl group	-H
GLC	N	-CH	-CH
				GLD	N	-H	-H
GLE	N	-H	-Cl
				GLF	N	-H	-Br
GLG	N	-H	-F
				GLH	N	-H	-CH
GLI	N	-H	-CF
				GLJ	N	-H	-OCH
GLK	N	-H	-OCHCH
				GLL	N	-H	-OCF
GLM	N	-H	-tert-butyl
				GLN	N	-H	-isopropyl group

TABLE XXI

And pharmaceutically acceptable salts thereof, wherein:

compound (I)	X	R	R	R
					GLO	S	-CH	-Cl	-F
GLP	S	-CH	-Cl	-Cl
					GLQ	S	-CH	-Cl	-CH
GLR	S	-CH	-F	-F
					GLS	S	-CH	-F	-Cl
GLT	S	-CH	-F	-CH
					GLU	S	-CF	-Cl	-F
GLV	S	-CF	-Cl	-Cl
					GLW	S	-CF	-Cl	-CH
GLX	S	-CF	-F	-F
					GLY	S	-CF	-F	-Cl
GLZ	S	-CF	-F	-CH
					GMA	S	-Cl	-Cl	-F
GMB	S	-Cl	-Cl	-Cl
					GMC	S	-Cl	-Cl	-CH
GMD	S	-Cl	-F	-F

GME	S	-Cl	-F	-Cl
					GMF	S	-Cl	-F	-CH
GMG	NH	-CH	-Cl	-F
					GMH	NH	-CH	-Cl	-Cl
GMI	NH	-CH	-Cl	-CH
					GMJ	NH	-CH	-F	-F
GMK	NH	-CH	-F	-Cl
					GML	NH	-CH	-F	-CH
GMM	NH	-CF	-Cl	-F
					GMN	NH	-CF	-Cl	-Cl
GMO	NH	-CF	-Cl	-CH
					GMP	NH	-CF	-F	-F
GMQ	NH	-CF	-F	-Cl
					GMR	NH	-CF	-F	-CH
GMS	NH	-Cl	-Cl	-F
					GMT	NH	-Cl	-Cl	-Cl
GMU	NH	-Cl	-Cl	-CH
					GMV	NH	-Cl	-F	-F
GMW	NH	-Cl	-F	-Cl
					GMX	NH	-Cl	-F	-CH
GMY	O	-CH	-Cl	-F
					GMZ	O	-CH	-Cl	-Cl
GNA	O	-CH	-Cl	-CH
					GNB	O	-CH	-F	-F
GNC	O	-CH	-F	-Cl
					GND	O	-CH	-F	-CH
GNE	O	-CF	-Cl	-F
					GNF	O	-CF	-Cl	-Cl
GNG	O	-CF	-Cl	-CH
					GNH	O	-CF	-F	-F
GNI	O	-CF	-F	-Cl

GNJ	O	-CF	-F	-CH
					GNK	O	-Cl	-Cl	-F
GNL	0	-Cl	-Cl	-Cl
					GNM	O	-Cl	-Cl	-CH
GNN	O	-Cl	-F	-F
					GNO	O	-Cl	-F	-Cl
GNP	O	-Cl	-F	-CH

TABLE XXII

And pharmaceutically acceptable salts thereof, wherein:

Compound (I)	X	R	R	R
					GNQ	S	-CH	-Cl	-F
GNR	S	-CH	-Cl	-Cl
					GNS	S	-CH	-Cl	-CH
GNT	S	-CH	-F	-F
					GNU	S	-CH	-F	-Cl
GNV	S	-CH	-F	-CH
					GNW	S	-CF	-Cl	-F

GNX	S	-CF	-Cl	-Cl
					GNY	S	-CF	-Cl	-CH
GNZ	S	-CF	-F	-F
					GOA	S	-CF	-F	-Cl
GOB	S	-CF	-F	-CH
					GOC	S	-Cl	-Cl	-F
GOD	S	-Cl	-Cl	-Cl
					GOE	S	-Cl	-Cl	-CH
GOF	S	-Cl	-F	-F
					GOG	S	-Cl	-F	-Cl
GOH	S	-Cl	-F	-CH
					GOI	NH	-CH	-Cl	-F
GOJ	NH	-CH	-Cl	-Cl
					GOK	NH	-CH	-Cl	-CH
GOL	NH	-CH	-F	-F
					GOM	NH	-CH	-F	-Cl
GON	NH	-CH	-F	-CH
					GOO	NH	-CF	-Cl	-F
GOP	NH	-CF	-Cl	-Cl
					GOQ	NH	-CF	-Cl	-CH
GOR	NH	-CF	-F	-F
					GOS	NH	-CF	-F	-Cl
GOT	NH	-CF	-F	-CH
					GOU	NH	-Cl	-Cl	-F
GOV	NH	-Cl	-Cl	-Cl
					GOW	NH	-Cl	-Cl	-CH
GOX	NH	-Cl	-F	-F
					GOY	NH	-Cl	-F	-Cl
GOZ	NH	-Cl	-F	-CH
					GPA	O	-CH	-Cl	-F
GPB	O	-CH	-Cl	-Cl

GPC	O	-CH	-Cl	-CH
					GPD	O	-CH	-F	-F
GPE	O	-CH	-F	-Cl
					GPF	O	-CH	-F	-CH
GPG	O	-CF	-Cl	-F
					GPH	O	-CF	-Cl	-Cl
GPI	O	-CF	-Cl	-CH
					GPJ	O	-CF	-F	-F
GPK	O	-CF	-F	-Cl
					GPL	O	-CF	-F	-CH
GPM	O	-Cl	-Cl	-F
					GPN	0	-Cl	-Cl	-Cl
GPO	O	-Cl	-Cl	-CH
					GPP	O	-Cl	-F	-F
GPQ	O	-Cl	-F	-Cl
					GPR	O	-Cl	-F	-CH

4.1 definition

As used herein, the terms used above have the following meanings:

″-(C₁-C₁₀) Alkyl "means a straight or branched chain non-cyclic hydrocarbon having 1 to 10 carbon atoms. Representative straight chain- (C)₁-C₁₀) Alkyl includes-methyl, -ethyl, -n-propyl, -n-butyl, -n-pentyl, -n-hexyl, -n-heptyl, -n-octyl-n-nonyl and-n-decyl. Representative branched chain- (C)₁-C₁₀) Alkyl includes-isopropyl, -sec-butyl, -isobutyl, -tert-butyl, -isopentyl, -neopentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1-dimethylpropyl, 1, 2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 3-ethylbutyl, 1-dimethylbutyl, 1, 2-dimethylbutyl, 1, 3-dimethylbutyl, 2-dimethylbutyl, 2, 3-dimethylbutyl, 3-dimethylbutyl, 1-methylhexyl, 2-methylhexyl, 3-methylbutyl, 2-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 3-ethylbutyl, 1-methylhexyl, 2, 4-methylhexyl, 5-methylhexyl, 1, 2-dimethylpentyl, 1, 3-dimethylpentyl, 1, 2-dimethylhexyl, 1, 3-dimethylhexyl, 3-dimethylhexyl, 1, 2-dimethylheptyl, 1, 3-dimethylheptyl and 3, 3-dimethylheptyl.

″-(C₁-C₆) Alkyl "means a straight or branched non-cyclic hydrocarbon having 1 to 6 carbon atoms. Representative straight chain- (C)₁-C₆) Alkyl includes-methyl, -ethyl, -n-propyl, -n-butyl, -n-pentyl and-n-hexyl. Representative branched chain- (C)₁-C₆) Alkyl groups include-isopropyl, -sec-butyl, -isobutyl, -tert-butyl, -isopentyl, -neopentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1-dimethylpropyl, 1, 2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 3-ethylbutyl, 1-dimethylbutyl, 1, 2-dimethylbutyl, 1, 3-dimethylbutyl, 2-dimethylbutyl, 2, 3-dimethylbutyl, and 3, 3-dimethylbutyl.

″-(C₁-C₄) Alkyl "means a straight or branched non-cyclic hydrocarbon having 1 to 4 carbon atoms. Representative straight chain- (C)₁-C₄) Alkyl groups include-methyl, -ethyl, -n-propyl and-n-butyl. Representative branched chain- (C)₁-C₄) Alkyl groups include-isopropyl, -sec-butyl, -isobutyl, and-tert-butyl.

″-(C₂-C₁₀) Alkenyl "means a straight or branched chain non-cyclic hydrocarbon having 2 to 10 carbon atoms and including at least one carbon-carbon double bond. Representative straight and branched chains (C) ₂-C₁₀) Alkenyl includes-vinyl, -allyl, -1-butenyl, -2-butenyl, -isobutenyl, -1-pentenyl, -2-pentenyl, -3-methyl-1-butenyl, -2-methyl-2-butenyl, -2, 3-dimethyl-2-butenyl, -1-hexenyl, -2-hexenyl, -3-hexenyl, -1-heptenyl, -2-heptenyl, -3-heptenyl, -1-octenyl, -2-octenyl, -3-octenyl, -1-nonenyl, -2-nonenyl, -3-nonenyl, -1-decenyl, -2-decenyl, -3-decenyl, and the like.

″-(C₂-C₆) Alkenyl "means a straight or branched chain non-cyclic hydrocarbon having 2 to 6 carbon atoms and including at least one carbon-carbon double bond. Representative straight and branched chains (C)₂-C₆) Alkenyl includes-vinyl, -allyl, -1-butenyl, -2-butenyl, -isobutenyl, -1-pentenyl, -2-pentenyl, -3-methyl-1-butenyl, -2-methyl-2-butenyl, -2, 3-dimethyl-2-butenyl, -1-hexenyl, 2-hexenyl, 3-hexenyl, and the like.

″-(C₂-C₁₀) Alkynyl "means a straight or branched non-cyclic hydrocarbon having 2 to 10 carbon atoms and including at least one carbon-carbon triple bond. Representative straight and branched chains- (C)₂-C₁₀) Alkynyl includes-ethynyl, -propynyl, -1-butynyl, -2-butynyl, -1-pentynyl, -2-pentynyl, -3-methyl-1-butynyl, -4-pentynyl, -1-hexynyl, -2-hexynyl, -5-hexynyl, -1-heptynyl, -2-heptynyl, -6-heptynyl, -1-octynyl, -2-octynyl, -7-octynyl, -1-nonynyl, -2-nonynyl, -8-nonynyl, -1-decynyl, -2-decynyl, -9-decynyl, and the like.

″-(C₂-C₆) Alkynyl "means a straight or branched non-cyclic hydrocarbon having 2 to 6 carbon atoms and including at least one carbon-carbon triple bond. Representative straight and branched chains (C)₂-C₆) Alkynyl includes-ethynyl, -propynyl, -1-butynyl, -2-butynyl-1-pentynyl, -2-pentynyl, -3-methyl-1-butynyl, -4-pentynyl, -1-hexynyl, -2-hexynyl, -5-hexynyl and the like.

″-(C₃-C₁₀) Cycloalkyl "means a saturated cyclic hydrocarbon having 3 to 10 carbon atoms. Representative of (C)₃-C₁₀) Cycloalkyl is-cyclopropyl, -cyclobutyl, -cyclopentyl, -cyclohexyl, -cycloheptyl, -cyclooctyl, -cyclononyl, and-cyclodecyl.

″-(C₃-C₈) Cycloalkyl "means a saturated cyclic hydrocarbon having 3 to 8 carbon atoms. Representative of (C)₃-C₈) Cycloalkyl includes-cyclopropyl, -cyclobutyl, -cyclopentyl, -cyclohexyl, -cycloheptyl and-cyclooctyl.

″-(C₈-C₁₄) Bicycloalkyl "means a bicyclic hydrocarbon ring system having 8 to 14 carbon atoms and at least one saturated cycloalkyl ring. Representative of- (C)₈-C₁₄) Bicyclic alkyl groups include-indanyl, -1, 2, 3, 4-tetrahydronaphthyl, -5, 6, 7, 8-tetrahydronaphthyl, -perhydronaphthyl, and the like.

″-(C₈-C₁₄) Tricycloalkyl "means a tricyclic hydrocarbon ring system having from 8 to 14 carbon atoms and at least one saturated ring. Representative of- (C) ₈-C₁₄) The tricycloalkyl group includes-pyrenyl, -1, 2, 3, 4-tetrahydroanthracenyl, -perhydroanthracenyl-aceanthryl, -1, 2, 3, 4-tetrahydrophenanthrenyl, -5, 6, 7, 8-tetrahydrophenanthrenyl, -perhydrophenanthrenyl and the like.

″-(C₅-C₁₀) Cycloalkenyl "means a cyclic non-aromatic hydrocarbon having at least one carbon-carbon double bond and 5 to 10 carbon atoms in the ring system. Representative of (C)₅-C₁₀) Cycloalkenyl includes-cyclopentenyl, -cyclopentadienyl, -cyclohexenyl, -cyclohexadienyl, -cycloheptenyl, -cycloheptadienyl, -cycloheptatrienyl, -cyclooctenyl, -cyclooctadienyl, -cyclooctatrienyl, -cyclooctatetraenyl, -cyclononenyl, -cyclodecenyl, -cyclodecadienyl and the like.

″-(C₅-C₈) Cycloalkenyl "means a cyclic non-aromatic hydrocarbon having at least one carbon-carbon double bond and 5 to 8 carbon atoms in the ring system. Representative of (C)₅-C₈) Cycloalkenyl includes-cyclopentenyl, -cyclopentadienyl, -cyclohexenyl, -cyclohexadienyl, -cycloheptenyl, -cycloheptadienyl, -cycloheptatrienyl, -cyclooctenyl, -cyclooctadienyl, -cyclooctatrienyl, -cyclooctatetraenyl, and the like.

″-(C₈-C₁₄) Bicycloalkenyl "means a bicyclic hydrocarbon ring system having at least one carbon-carbon double bond and 8 to 14 carbon atoms in each ring. Representative of- (C) ₈-C₁₄) Bicycloalkenyl includes-indenyl, -pentalenyl, -naphthyl, -azulenyl, -heptatrienyl (-heptalenyl), -1, 2, 7, 8-tetrahydronaphthyl, and the like.

″-(C₈-C₁₄) Tricycloalkenyl "means a tricyclic hydrocarbon ring system having at least one carbon-carbon double bond and 8 to 14 carbon atoms in each ring.

Representative of- (C)₈-C₁₄) Tricycloalkenyl includes-anthryl, -phenanthryl, -phenalenyl, -acenaphthenyl, as-indacenyl, s-indacenyl, and the like.

"- (3-to 7-membered) heterocycle" or "- (3-to 7-membered) heterocycle" means a 3-to 7-membered monocyclic heterocycle, which ring is a saturated, unsaturated, non-aromatic or aromatic ring. A 3-membered heterocyclic ring may contain up to 3 heteroatoms, while a 4-to 7-membered heterocyclic ring may contain up to 4 heteroatoms. Each heteroatom is independently selected from nitrogen (which may be quaternized), oxygen, and sulfur, including sulfoxides and sulfones. The- (3-to 7-membered) heterocyclic ring may be attached through a nitrogen or carbon atom. Representative- (3 to 7-membered) heterocycles include pyridyl, furyl, thienyl, pyrrolyl, oxazolyl, imidazolyl, thiazolyl, thiadiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, morpholinyl, pyrrolidinonyl, pyrrolidinyl, piperidinyl, piperazinyl, hydantoinyl, valerolactonyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydroindenyl, tetrahydropyrimidinyl, tetrahydrothienyl, tetrahydrothiopyranyl, and the like.

"- (3 to 5-membered) heterocyclic" or "- (3 to 5-membered) heterocyclic" means a 3 to 5-membered monocyclic heterocyclic ring which is a saturated, unsaturated, non-aromatic or aromatic ring. A3-membered heterocyclic ring may contain up to 3 heteroatoms, while a 4-to 5-membered heterocyclic ring may contain up to 4 heteroatoms. Each heteroatom is independently selected from nitrogen (which may be quaternized), oxygen, and sulfur, including sulfoxides and sulfones. The- (3-to 5-membered) heterocyclic ring may be attached through a nitrogen or carbon atom. Representative- (3 to 5-membered) heterocycles include furyl, thienyl, pyrrolyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, triazinyl, pyrrolidinonyl, pyrrolidinyl, hydantoinyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl and the like.

"- (7 to 10-membered) bicyclic heterocycle" or "- (7 to 10-membered) bicyclic heterocycle" means a 7 to 10-membered bicyclic heterocycle, which ring is a saturated, unsaturated, non-aromatic or aromatic ring. The (7-to 10-membered) bicyclic heterocycle contains 1-4 heteroatoms independently selected from nitrogen (which may be quaternized), oxygen, and sulfur, including sulfoxides and sulfones. The (7-to 10-membered) bicyclic heterocycle may be attached via a nitrogen or carbon atom. Representative- (7-to 10-membered) bicyclic heterocycles include-quinolyl, -isoquinolyl, -chromonyl, -coumarinyl, -indolyl, -indolizinyl, -benzo [ b ] furyl, -benzo [ b ] thienyl, -indazolyl, -purinyl, -4H-quinolizinyl, -isoquinolyl, -quinolyl, -naphthyridinyl, -carbazolyl, -beta-carbolinyl and the like.

″-(C₁₄) Aryl "means a 14-membered aromatic carbocyclic moiety, such as-anthracenyl or-phenanthrenyl.

"(5 to 10-membered) heteroaryl" means a 5-10 membered aromatic heterocyclic ring, including mono-and bicyclic ring systems, wherein at least one carbon atom of one or both rings of the ring system is replaced with a heteroatom independently selected from nitrogen, oxygen, and sulfur. One or both rings of the (5-to 10-membered) heteroaromatic ring contain at least one carbon atom. Representative- (5 to 10-membered) heteroaryl groups include pyridyl, furyl, benzofuryl, thienyl, benzothienyl, quinolyl, pyrrolyl, indolyl, oxazolyl, benzoxazolyl, imidazolyl, benzimidazolyl, thiazolyl, benzothiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiadiazolyl, triazinyl, cinnolinyl, naphthyridinyl and quinazolinyl.

″-CH₂By (halo) "is meant a methyl group in which one hydrogen on the methyl group has been replaced by a halogen. Representative of-CH₂The (halo) group comprises-CH₂F、-CH₂Cl、-CH₂Br and-CH₂I。

"-CH (halo)₂"means a methyl group in which both hydrogens on the methyl group have been replaced with a halogen. Representative of-CH (halo)₂The group comprising-CHF₂、-CHCl₂、-CHBr₂CHBrCl, CHClI and-CHI₂。

"-C (halo)₃"means a methyl group in which each hydrogen on the methyl group has been replaced by a halogen. Representative of-C (halo) ₃The radicals comprising-CF₃、-CCl₃、-CBr₃and-CI₃。

"-halogen" or "-halo" means-F, -Cl, -Br, or-I.

The phrase "pyridyl" refers to

Wherein R is₁、R₂And n is as defined above for the benzoxazole piperazine compounds of formula (Ia, IIa and IIIa).

The phrase "pyrazinyl" refers to

Wherein R is₁、R₂And p is as defined above for the benzoxazole piperazine compounds of formula (Ib, IIa and IIIb).

The phrase "pyrimidinyl" means

Wherein R is₁、R₂And p is as defined above for the benzoxazole piperazine compounds of formulae (Ia), (IIa) and (IIIa).

The phrase "pyridazinyl" refers to

Wherein R is₁、R₂And p is as defined above for the benzoxazole piperazine compounds of formulae (Ib), (IIb) and (IIIb).

The phrase "thiazanyl" means

Wherein R is₁As defined above for the benzoxazole piperazine compounds of formulae (Ib), (IIb) and (IIIb).

The phrase "2- (3-chloropyridyl)" refers to

The phrase "2- (3-methylpyridyl)" means

The phrase "2- (3-CF)₃-pyridyl)' means

The phrase "2- (3-CHF)₂-pyridyl)' means

The phrase "2- (3-hydroxypyridyl)" refers to

The phrase "2- (3-nitropyridinyl)" refers to

The phrase "2- (3-cyanopyridyl)" refers to

The phrase "2- (3-bromopyridyl)" refers to

The phrase "2- (3-iodopyridyl)" refers to

The phrase "4- (5-chloropyrimidinyl)" means

The phrase "4- (5-methylpyrimidinyl)" means

The phrase "4- (5-fluoropyrimidinyl)" means

The phrase "2- (3-chloropyrazinyl)" means

The phrase "2- (3-methylpyrazinyl)" means

The phrase "2- (3-fluoropyrazinyl)" means

The phrase "3- (4-chloropyridazinyl)" means

The phrase "3- (4-methylpyridazinyl)" means

The phrase "3- (4-fluoropyridazinyl)" means

The phrase "5- (4-chloro-thiazanyl)" means

The phrase "5- (4-methylthiozanyl)" means

The phrase "2-pyrazinyl" means

The phrase "2-pyridazinyl" refers to

The phrase "4-thiazanyl" means

The phrase "5- (4-fluoro-thiazanyl)" means

The phrase "benzimidazolyl" refers to

Wherein R is₈、R₉And R₁₀As defined above for the benzoxazole piperazine compounds of formulae (IIa) and (IIb).

The phrase "benzothiazolyl" means

Wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formula (Ia) and (Ib).

The phrase "benzoxazolyl" means

Wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formula (IIIa) and (IIIb).

The term "animal" includes, but is not limited to, cows, monkeys, baboons, chimpanzees, horses, sheep, pigs, chickens, turkeys, quail, cats, dogs, mice, rats, rabbits, guinea pigs, and humans.

The phrase "pharmaceutically acceptable salt", when used herein, includes salts formed from acidic and basic nitrogen groups of one of the benzoxazole piperazine compounds. Exemplary salts include, but are not limited to, sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, biphosphate, isonicotinate, lactate, salicylate, bitartrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisic acid, fumarate, gluconate, glucarate (glucaronate), saccharinate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, and pamoate (i.e., 1, 1' -methylene-bis (2-hydroxy-3-naphthoate)) and the like. The term "pharmaceutically acceptable salts" also includes salts prepared from benzoxazole piperazine compounds having an acidic functional group (e.g., a carboxylic acid functional group) and a pharmaceutically acceptable inorganic or organic base. Suitable bases include, but are not limited to, hydroxides of alkali metals (such as sodium, potassium, and lithium); hydroxides of alkaline earth metals (such as calcium and magnesium); hydroxides of other metals (such as aluminum and zinc); ammonia and organic amines, such as unsubstituted or hydroxy-substituted mono-, di-or trialkylamines; dicyclohexylamine; tributylamine; pyridine; n-methylamine, N-ethylamine; a diethylamine; triethylamine; mono-, di-or tris (2-hydroxy-lower alkyl amines) such as mono-, di-or tris (2-hydroxyethyl) amine, 2-hydroxy-tert-butylamine or tris (hydroxymethyl) methylamine, N-di-lower alkyl-N- (hydroxy lower alkyl) -amines such as N, N-dimethyl-N- (2-hydroxyethyl) amine or tris (2-hydroxyethyl) amine; N-methyl-D-glucamine; and amino acids such as arginine, lysine, and the like.

The phrase "effective amount", when used in combination with a benzoxazole piperazine compound, refers to an amount effective for: (a) treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, emesis, a movement disorder or depression; or (b) inhibits VR1, mGluR1, or mGluR5 function in a cell.

The phrase "effective amount," when used in conjunction with another therapeutic agent, refers to an amount that provides the therapeutic effect of the therapeutic agent.

When a first group is "substituted with" one or more "second groups," one or more hydrogen atoms of the first group are replaced with a corresponding number of second groups. When the number of the second groups is 2 or more than 2, each of the second groups may be the same or different. In one embodiment, the number of second groups is 1 or 2. In another embodiment, the number of second groups is 1.

The term "DMSO" refers to dimethylsulfoxide.

The term "DCM" refers to dichloromethane.

The term "UI" refers to urinary incontinence.

The term "IBD" refers to inflammatory bowel disease.

The term "IBS" refers to irritable bowel syndrome.

The term "ALS" refers to amyotrophic lateral sclerosis.

The phrases "treating" and "treatment" include amelioration or cessation of pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression, or a symptom thereof.

The phrases "preventing" and "prevention" include avoiding the occurrence of the following symptoms: pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression, or a symptom thereof.

4.2 preparation method of benzoxazole piperazine compound

The benzoxazole piperazine compounds may be prepared using conventional organic synthesis methods or by the following exemplary methods shown in the following schemes.

4.2.1 preparation of compounds in which x is 1 and A is-C (O) -NR₄A process for preparing a benzoxazole piperazine compound of formulae (Ia) and (Ib)

Benzoxazole piperazine compounds of the formulae (Ia) and (Ib), where x is 1, A is-C (O) -NR₄-and R₄is-H, can be obtained by the following exemplary method shown in scheme A:

benzoxazoles of the formulae (Ia) and (Ib)

Piperazine-like compounds

Wherein Ar is₁、R₃、R₈、R₉And m is as defined above for the benzoxazole piperazine compounds of formula (Ia) and (Ib).

Procedure A

To the resulting solution, the compound of formula A (about 2mmol) was added by dissolving the compound of formula B (about 2mmol) in an aprotic organic solvent (about 3mL) and the resulting reaction mixture was stirred for about 10 minutes. Then removing the solvent under reduced pressure to obtain the benzoxazole piperazine compounds (Ia) and (Ib), wherein x is 1, and A is-C (O) -NR₄-and R₄is-H. The benzoxazole piperazine compounds of formula (Ia) and (Ib) can be purified on a silica gel column eluting with 5: 95 ethyl acetate/hexane.

The compound of formula B can be obtained as shown in scheme B below:

wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formula (Ia) and (Ib).

Procedure B

The compound of formula D (about 0.75 equivalents) (about 0.04M) in an aprotic organic solvent is cooled to about 0 ℃. To this cooled solution is slowly added a solution (about 0.4M) of the compound of formula C (about 0.75 equivalents) in an aprotic organic solvent. The resulting mixture was stirred at 0 ℃ for about 5 minutes, and then about 0.75 equivalents of triethylamine was added to the reaction mixture. The reaction mixture was allowed to warm to room temperature and then the solvent was removed under reduced pressure to give the compound of formula B. The compound of formula D is commercially available from Sigma-Aldrich, St.Louis, MO (www.sigma-aldrich.com). The compounds of formula C are commercially available or can be prepared by the exemplary methods shown in scheme C below.

Wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formula (Ia) and (Ib).

Procedure C

To a stirred solution of aniline U (about 74mmol) and potassium thiocyanate (about 148mmol) in about 100mL of glacial acetic acid was added dropwise a solution of bromine (about 74mmol) in about 25mL of glacial acetic acid. The flask containing the acetic acid solution of bromine was then rinsed with about 15mL of acetic acid and combined with the aniline U solution. The resulting reaction mixture was stirred vigorously at room temperature for about 2h to about 24 h. The reaction mixture was then poured into crushed ice (about 500mL) and the pH of the resulting mixture was adjusted to a value of about 10 using ammonium hydroxide to give a precipitate. The resulting precipitate was collected by filtration and recrystallized from toluene to give the compound of formula C.

The compounds of formula U are commercially available or may be prepared by methods well known to those skilled in the art.

The compound of formula a can be obtained as shown in scheme D below:

wherein R is₁、R₂、R₃M, n and p are as defined above for the benzoxazole piperazine compounds of formulae (Ia) and (Ib), and X is halogen.

Procedure D

The compound of formula F1-F5 (about 20mmol) is reacted with the compound of formula E (about 27.5mmol) in about 15mL DMSO in the presence of triethylamine (about 30mmol), optionally with heating, for about 24h to provide the compound of formula A. The compound of formula a is isolated from the reaction mixture and then purified. In one embodiment, the compound of formula a is purified by column chromatography or recrystallization.

The compounds of formulae E and F are commercially available or can be prepared by methods well known to those skilled in the art. A compound of formula E (wherein m is 0) and a compound of formula E (wherein m is 1 and R₃Is (R) -CH₃Or (S) -CH₃) Commercially available from Sigma-Aldrich, St.Louis, MO (www.sigma-aldrich.com). In one embodiment, X is bromide, chloride or iodide.

Benzoxazole piperazine compounds of the formulae (Ia) and (Ib), where x is 1, A is-C (O) -NR₄-and R₄Is- (C)₁-C₆) An alkyl group, obtainable by the exemplary method shown in scheme E below:

Benzoxazole piperazine compounds of formula (Ia) and (Ib)

Wherein Ar is₁、R₃、R₄、R₈、R₉And m is as defined above for the benzoxazole piperazine compounds of formula (Ia) and (Ib) and X is halogen.

Procedure E

To a benzoxazole piperazine compound of formula (Ia) or (Ib) (wherein x is 1, A is-C (O) -NR) obtained as described above in scheme A at 0 deg.C₄-and R₄is-H) (about 1 equivalent)To the DMF solution, NaH (about 2 equivalents) in DMF was added. The resulting reaction mixture was allowed to warm to room temperature for about 1 h. To the resulting mixture was added about 1.2 equivalents of alkyl halide, R₄X, stirring the resulting reaction mixture until the benzoxazole piperazine compounds of formula (Ia) and (Ib) are formed, wherein X is 1, A is-C (O) -NR₄-and R₄Is- (C)₁-C₆) An alkyl group. Using conventional analytical techniques including, but not limited to, High Pressure Liquid Chromatography (HPLC), column chromatography, Thin Layer Chromatography (TLC), column chromatography, gas chromatography, mass spectrometry and nuclear magnetic resonance spectroscopy (e.g., HPLC)¹H and¹³c NMR), the progress of the reaction can be monitored. Then isolating and purifying the benzoxazole piperazine compounds of formula (Ia) and (Ib) wherein x is 1 and A is-C (O) -NR₄-and R₄Is- (C)₁-C₆) An alkyl group. In one embodiment, the benzoxazole piperazine compounds of formulas (Ia) and (Ib) are those wherein x is 1, A is-C (O) -NR₄-and R ₄Is- (C)₁-C₆) Alkyl, isolated by removal of the solvent under reduced pressure. In another embodiment, the benzoxazole piperazine compounds of formulas (Ia) and (Ib) wherein x is 1 and A is-C (O) -NR₄-and R₄Is- (C1-C)₆) Alkyl, isolated by extraction. Benzoxazole piperazine compounds of the formulae (Ia) and (Ib), where x is 1, A is-C (O) -NR₄-and R₄Is- (C)₁-C₆) Alkyl groups, can be purified, for example, by column chromatography or recrystallization.

4.2.2 preparation of compounds in which x is 1 and A is-C (S) -NR₄Are disclosed as a process for preparing benzoxazole piperazine compounds of formulae (Ia) and (Ib)

Benzoxazole piperazine compounds of the formulae (Ia) and (Ib), where x is 1, A is-C (S) -NR₄-and R₄to-H, can be obtained by the following exemplary method of scheme F:

benzoxazole piperazine compounds of formula (Ia) and (Ib)

Wherein Ar is₁、R₃、R₈、R₉And m is as defined above for the benzoxazole piperazine compounds of formula (Ia) and (Ib).

Procedure F

A compound of formula C (about 2mmol), 1' -thiocarbonyldiimidazole (about 2mmol) (commercially available from Sigma-Aldrich, st. louis, MO (www.sigma-Aldrich. com)) and 4-Dimethylaminopyridine (DMAP) (commercially available from Sigma-Aldrich, st. louis, MO (www.sigma-Aldrich. com)) were suspended in DMSO (about 3mL) at room temperature and the resulting mixture was heated at about 100 ℃ for about 6 h. The resulting reaction mixture was then allowed to cool to room temperature, the compound of formula a (about 2mmol) was added to the reaction mixture, and the reaction mixture was heated to about 100 ℃ for about 16 h. Then removing the solvent under reduced pressure to obtain the benzoxazole piperazine compounds (Ia) and (Ib), wherein x is 1, and A is-C (S) -NR ₄-and R₄is-H. The benzoxazole piperazine compounds of formula (Ia) and (Ib) can be purified on a silica gel column eluting with 5: 95 ethyl acetate/hexane.

Can be used for obtaining benzoxazole piperazine compounds of formula (Ia) and (Ib) (wherein x is 1, A is-C (O) -NR)₄-and R₄Is- (C)₁-C₆) Alkyl) with the benzoxazole piperazine compounds of formulae (Ia) and (Ib) (where x is 1, A is-C (S) -NR) obtained as described in scheme F above₄-and R₄is-H) in place of the benzoxazole piperazine compounds of the formulae (Ia) and (Ib) (wherein x is 1 and A is-C (O) -NR₄-and R₄is-H) to obtain benzoxazole piperazine compounds of formula (Ia) and (Ib), wherein x is 1, A is-C (S) -NR₄-and R₄Is- (C)₁-C₆) An alkyl group.

4.2.3 Process for the preparation of benzoxazole piperazine compounds of the formulae (Ia) and (Ib) where X is 0,

benzoxazole piperazine compounds of formulae (Ia) and (Ib), wherein x is 0, can be obtained by the following exemplary method as shown in scheme G below:

benzoxazole piperazine compound of formula (Ia) or (Ib)

Wherein Ar is₁、R₃、R₈、R₉And m is as defined above for the benzoxazole piperazine compounds of formula (Ia) and (Ib).

Process G

The compound of formula A (about 1mmol) and the compound of formula G (about 1mmol) are dissolved in DMSO (about 3mL) and heated at a temperature of about 140 ℃ to 150 ℃ for about 12 h. The mixture was cooled to room temperature and the solvent removed under reduced pressure to give a residue which was purified by flash chromatography on silica gel (gradient eluent from 2: 98 methanol: DCM-6: 94 methanol: DCM) to give the benzoxazole piperazine compounds of formula (Ia) and (Ib) where x is 0.

The compound of formula a can be obtained as shown in scheme D above.

The compounds of formula G are commercially available or may be prepared by methods well known to those skilled in the art. An exemplary process for preparing a compound of formula G is shown in scheme H below:

wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formula (Ia) and (Ib).

Process H

A compound of formula Z (about 5 to about 10mmol) and Carbodiimide (CDI) (commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma-Aldrich. com)) (about 2 equivalents) were dissolved in THF (about 50 to about 70mL) and the resulting reaction mixture was mixed at reflux temperatureThe compound was heated for about 4 hours. The reaction mixture was then concentrated under reduced pressure to give a residue. Ethyl acetate (about 50mL) was added to the residue and the remaining insoluble material was collected by filtration and washed with ethyl acetate to give the compound of formula AA. Then, the ratio was determined according to the standard in j.med.chem.40: 586-₃Reaction to give the compound of formula BB. The compounds of formula Z are commercially available or can be prepared by methods well known to those skilled in the art. An exemplary method of obtaining a compound of formula Z is shown in scheme I below:

wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formula (Ia) and (Ib).

Scheme I

The thiol CC (about 12mmol) is dissolved in concentrated sulfuric acid (about 10mL) at 0 deg.C and the resulting solution is cooled to a temperature of about-13 deg.C to about-15 deg.C. About 1mL of 70% nitric acid was added to the resulting solution over about 30 minutes, and the resulting reaction mixture was stirred at a temperature between about-13 ℃ and about-15 ℃ for about 2 hours. The reaction mixture was then poured into ice water (about 100mL), neutralized with 5% -10% aqueous sodium hydroxide and extracted with about 50mL of chloroform. The chloroform layer was separated from the aqueous layer and the chloroform was then removed under reduced pressure to give a residue which was purified by flash chromatography (silica gel column and chloroform eluent) to give the compound of formula DD. The compound of formula DD was dissolved in ethanol (about 50mL) and hydrogenated at room temperature for about 12 hours using 10% palladium on carbon as the catalyst. The catalyst was removed by filtration and the ethanol removed under reduced pressure to give a residue which was purified by flash chromatography (silica gel, eluting with 20: 1 dichloromethane: methanol) to give the compound of formula EE. The compounds of formula CC are commercially available or may be prepared by methods well known to those skilled in the art.

4.2.4 method for preparing benzoxazole piperazine compounds of formula (IIa) and (IIb) where X is 0

The benzoxazole piperazine compounds of formula (Ia) and (Ib), wherein x is 0, can be obtained by similar methods as described in scheme G4.2.3 above, but using a compound of formula H as shown below,

Wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formulae (IIa) and (IIb), instead of the compound of formula G as shown in scheme J below:

benzoxazole piperazine compounds of formula (IIa) or (IIb)

Wherein Ar is₁、R₃、R₈、R₉And m is as defined above for the benzoxazole piperazine compounds of formula (IIa) and (IIb), to obtain the benzoxazole piperazine compound of formula (IIa) (wherein R is₁₀is-H) and benzoxazole piperazine compounds of formula (IIb) (wherein x is 0 and R₁₀is-H).

Procedure J

The compound of formula a (about 1mmol) and the compound of formula H (about 1mmol) are dissolved in toluene or p-xylene in a sealed tube and heated at a temperature of about 140 ℃ to 150 ℃ for about 3 days. The mixture was cooled to room temperature and the solvent was removed under reduced pressure to give a residue which was purified by flash chromatography (silica gel, eluting with a gradient eluent from 2% methanol: dichloromethane to 6% methanol: dichloromethane) to give the benzoxazole piperazine compounds of formula (IIa) and (IIb) wherein x is 0.

The compound of formula a can be obtained as shown in scheme D above.

The compounds of formula H are commercially available or can be prepared by methods well known to those skilled in the art. An exemplary method for preparing a compound of formula H is shown in scheme K below:

Wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formulae (IIa) and (IIb).

Procedure K

A compound of formula I (about 5 to about 10mmol) and Carbodiimide (CDI) (commercially available from Sigma-Aldrich, st. louis, MO (www.sigma-Aldrich. com)) (about 2 equivalents) were dissolved in THF (about 50 to about 70mL) and the resulting reaction mixture was heated at reflux temperature for about 4 hours. The reaction mixture was then concentrated under reduced pressure to give a residue. Ethyl acetate (about 50mL) was added to the residue and the resulting insoluble material was collected by filtration and washed with ethyl acetate to give the compound of formula J. Then the ratio was determined according to the standard in j.med.chem.40: 586-₃And reacting to obtain the compound shown in the formula H. The compounds of formula I are commercially available or may be prepared by methods well known to those skilled in the art. An exemplary method for obtaining a compound of formula I is shown in scheme L below:

wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formulae (IIa) and (IIb).

Procedure L

Aniline hydrochloride V (about 12mmol) was dissolved in concentrated sulfuric acid (about 10mL) at 0 deg.C and the resulting solution was cooled to a temperature of about-13 deg.C to about-15 deg.C. About 1mL of 70% nitric acid was added to the resulting solution over about 30 minutes, and the resulting reaction mixture was stirred at a temperature of about-13 ℃ to about-15 ℃ for about 2 hours. The reaction mixture was then poured into ice water (about 100mL), neutralized with 5% -10% aqueous sodium hydroxide and extracted with about 50mL of chloroform. The chloroform was separated from the aqueous layer and removed under reduced pressure to give a residue which was purified by flash chromatography (silica gel column and chloroform eluent) to give the compound of formula W. The compound of formula W was dissolved in ethanol (about 50mL) and hydrogenated at room temperature for about 12 hours using 10% palladium on carbon as the catalyst. The catalyst was removed by filtration and the ethanol removed under reduced pressure to give a residue which was purified by flash chromatography (silica gel, eluting with 20: 1 dichloromethane: methanol) to give the compound of formula I. The compounds of formula V are commercially available or may be prepared by methods well known to those skilled in the art.

Can be obtained by reaction with the benzoxazole piperazine compounds described in scheme J above for obtaining the formula (IIa) and (IIb) (wherein x is 0 and R₁₀is-H), but using a compound of the formula K shown below

Wherein R is₈And R₉Benzoxazole piperazine compounds of the formulae (IIa) and (IIb) as above and R₁₀Is- (C)₁-C₆) Alkyl, instead of the compound of formula H, to obtain a benzoxazole piperazine compound of formula (IIa) (wherein R is₁₀Is- (C)₁-C₄) Alkyl) and benzoxazole piperazine compounds of the formula (IIb) (where x is 0 and R)₁₀Is- (C)₁-C₄) Alkyl groups). Compounds of formula K can be obtained as described in scheme M below

Wherein R is₈And R₉R is as defined above for the benzoxazole piperazine compounds of the formulae (IIa) and (IIb)₁₀Is- (C)₁-C₆) Alkyl and X are halogen.

Procedure M

NaH (ca. 2 equivalents) was added to the DMF solution of the compound of formula H at 0 deg.C, and the resulting mixture was stirred and allowed to warm to room temperature over 1 hour. Then the alkyl halide, R₁₀-X, (about 1.2 equivalents) is added to the solution and the resulting reaction mixture is stirred until the compound of formula K is produced. In one embodiment, the alkyl halide is an alkyl iodide. The compound of formula K can be formed by analytical methods well known to those skilled in the art, including, but not limited to, liquid chromatography, column chromatography, gas chromatography, thin layer chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy (e.g., as described above) ¹H and¹³c NMR) was monitored. Water is then added to the reaction mixture to produce a precipitate of the compound of formula K, which is then filtered, collected and dried.

The compound of formula H can be obtained as described in scheme K above.

4.2.5 preparation of compounds in which x is 1 and A is-C (O) -NR₄Is of the formula (II)_B) Process for benzoxazole piperazine compound

Benzoxazole piperazine compounds of formula (Ia) and (Ib) (where x is 1 and A is-C (O) -NR) can be obtained by the procedure described in scheme A above₄-and R₄is-H), but using a compound of the formula L shown below

Wherein R is₈And R₉As defined above for the benzoxazole piperazine compound of formula (IIb), instead of the compound of formula B, a benzoxazole piperazine compound of formula (IIb) is obtained, wherein x is 1, a is-c (o) -NR₄-，R₄is-H and R₁₀is-H.

By a method analogous to that described in scheme B, section 4.2.1 for obtaining the compound of formula B, but using a compound of formula M as shown below

Wherein R is₈And R₉Instead of the compound of formula C, the compound of formula L can be obtained as defined above for the benzoxazole piperazine compound of formula (IIb). The compounds of formula M are commercially available or may be prepared by methods well known to those skilled in the art. An exemplary method for obtaining a compound of formula M is shown in scheme N below:

Wherein R is₈And R₉Benzoxazole piperazine compounds of the formula (IIb) as above

Procedure N

The compound of formula H (about 1mmol) (prepared as described in scheme K above) was dissolved in excess ammonia water in a sealed tube and heated at a temperature of about 140-150 ℃ for about 3 days. The mixture was cooled to room temperature and the solvent was removed under reduced pressure to give a residue. In another embodiment, the mixture is cooled to room temperature, extracted with an organic solvent, the organic phase is separated from the aqueous phase, and the organic solvent is removed under reduced pressure to give a residue. The residue is then purified to give the compound of formula M. In one embodiment, the residue is purified by recrystallization. In another embodiment, the residue is purified using flash chromatography.

Benzoxazole piperazine compounds of formula (IIb) wherein x is 1, A is-C (O) -NR₄-，R₄is-H and R₁₀Is- (C)₁-C₄) Alkyl, obtainable by reaction with a benzoxazole piperazine compound of formula (IIb) wherein x is 1, A is-C (O) -NR₄-，R₄is-H and R₁₀is-H) in a similar manner, but using a compound of formula N as shown below

Wherein R is₈、R₉And R₁₀As defined above for the benzoxazole piperazine compound of formula (IIb), instead of the compound of formula L. By a process analogous to that used to obtain the compound of formula L, but using a compound of formula O as shown below

Wherein R is₈、R₉And R₁₀Instead of the compound of formula M, the compound of formula N can be obtained as defined above for the benzoxazole piperazine compound of formula (IIb). The compound of formula O can be obtained as shown in scheme N below:

wherein R is₈、R₉And R₁₀As defined above for the benzoxazole piperazine compound of formula (IIb).

Procedure N

NaH (ca. 2 equivalents) was added to the DMF solution of the compound of formula M at 0 deg.C, and the resulting mixture was stirred and allowed to warm to room temperature over 1 hour. Then the alkyl halide, R₁₀-X, (about 1 equivalent) is added to the solution and the resulting reaction mixture is stirred until a mixture of compound of formula O and compound of formula X is produced. In one embodiment, the alkyl halide is an alkyl iodide. The formation of compounds of formula O and compounds of formula X can be monitored by analytical methods well known to those skilled in the art, including but not limited to those described above. Water is then added to the reaction mixture to produce a precipitate of the compound of formula O and the compound of formula X, which is collected by filtration. The compound of formula O is then separated from the compound of formula X to provide the compound of formula O. Compounds of formula O and compounds of formula X may be isolated by analytical methods well known to those skilled in the art, including but not limited to column chromatography, preparative TLC, preparative HPLC and preparative GC.

By reaction with the benzazolyl piperazine compounds of formula (Ia) and (Ib) shown above in scheme E (where x is 1, A is-C (O) -NR)₄-and R₄Is- (C)₁-C₆) Alkyl) but with a benzoxazole piperazine compound of formula (IIb) prepared as described above (wherein x is 1, A is-C (O) -NR)₄-，R₄is-H and R₁₀is-H) in place of the benzoxazole piperazine compounds of the formulae (Ia) and (Ib) (wherein x is 1 and A is-C (O) -NR₄-and R₄is-H), benzoxazole piperazine compounds of formula (IIb) are obtained, wherein x is 1, A is-C (O) -NR₄-，R₄Is- (C)₁-C₆) Alkyl and R₁₀is-H.

By reaction with the benzazolyl piperazine compounds of formula (Ia) and (Ib) shown above in scheme E (where x is 1, A is-C (O) -NR)₄-and R₄Is- (C)₁-C₆) Alkyl) but with a benzoxazole piperazine compound of formula (IIb) prepared as described above (wherein x is 1, A is-C (O) -NR)₄-，R₄is-H and R₁₀Is- (C)₁-C₆) Alkyl) in place of the benzoxazole piperazine compounds of the formulae (Ia) and (Ib) (where x is 1 and A is-C (O) -NR)₄-and R₄is-H), benzoxazole piperazine compounds of formula (IIb) are obtained, wherein x is 1, A is-C (O) -NR₄-，R₄Is- (C)₁-C₆) Alkyl and R₁₀Is- (C)₁-C₄) An alkyl group.

4.2.6 preparation of a compound wherein x is 1 and A is-C (S) -NR₄Formula (II)_B) Process for preparing benzoxazole piperazine compound

By reacting with the benzazolyl piperazine compounds described in scheme F above for obtaining the formula (Ia) and (Ib) (where x is 1 and A is-C, (S) -NR₄-and R₄A similar process to that of-H), but replacing the compound of formula C with a compound of formula M, gives a benzoxazole piperazine compound of formula (IIb), wherein x is 1, A is-C (S) -NR₄-，R₄is-H and R₁₀is-H. The compounds of formula M may be obtained as described above.

By reacting with the compounds described in scheme F, section 4.2.2 above for obtaining benzoxazole piperazine compounds of formula (Ia) and (Ib) (wherein x is 1, A is-C (S) -NR)₄-and R₄A similar process to that of-H), but replacing the compound of formula C with a compound of formula O, gives a benzoxazole piperazine compound of formula (IIb), wherein x is 1, A is-C (S) -NR₄-，R₄is-H and R₁₀Is- (C)₁-C₄) An alkyl group. The compounds of formula O can be obtained as described above.

By reaction with the benzazolyl piperazine compounds described in scheme E above for obtaining the formula (Ia) and (Ib) (where x is 1, A is-C (O) -NR)₄-and R₄Is- (C)₁-C₆) Alkyl) with the benzoylpiperazine compound of the formula (IIa) prepared as described above (where A is-C (S) -NR)₄-，R₄is-H and R₁₀is-H) in place of the benzoxazole piperazine compounds of the formulae (Ia) and (Ib) (wherein x is 1 and A is-C (O) -NR₄-and R₄is-H), benzoxazole piperazine compounds of formula (IIb) are obtained, wherein x is 1, A is-C (S) -NR ₄-，R₄Is- (C)₁-C₆) Alkyl and R₁₀is-H.

By reaction with the benzazolyl piperazine compounds described in scheme E above for obtaining the formula (Ia) and (Ib) (where x is 1, A is-C (O) -NR)₄-and R₄Is- (C)₁-C₆) Alkyl) by a similar process but using a preparation as described aboveThe benzoylpiperazine compound of formula (IIa) is prepared (wherein A is-C (S) -NR)₄-，R₄is-H and R₁₀Is- (C)₁-C₄) Alkyl) in place of the benzoxazole piperazine compounds of the formulae (Ia) and (Ib) (where x is 1 and A is-C (O) -NR)₄-and R₄is-H), benzoxazole piperazine compounds of formula (IIb) are obtained, wherein x is 1, A is-C (S) -NR₄-，R₄Is- (C)₁-C₆) Alkyl and R₁₀Is- (C)₁-C₄) An alkyl group.

4.2.7 preparation of a compound wherein x is 1 and A is-C (O) -NR₄Is of the formula (III)_A) And (III)_B) Benzoxazole piperazine compound

By reacting with the compounds described in scheme A, section 4.2.1 above for obtaining benzoxazole piperazine compounds of formula (Ia) and (Ib) (wherein x is 1 and A is-C (O) -NR)₄) By a similar process to that described above, but using a compound of formula P as shown below

Wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formula (IIIa) and (IIIb), in place of the compound of formula B, benzoxazole piperazine compounds of formula (IIIa) and (IIIb) are obtained, wherein x is 1, A is-C (O) -NR₄-and R₄is-H.

By a similar procedure as described above for obtaining the compound of formula B in scheme B, but with a compound of formula Q as shown below

Wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formulae (IIIa) and (IIIb), instead of the compound of formula C, a compound of formula P is obtainedA compound (I) is provided. The compounds of formula Q are commercially available or can be prepared by methods well known to those skilled in the art. By a similar procedure as described above for obtaining the compound of formula BB, but with the compound of formula HH as shown below

Instead of the compound of formula Z, a compound of formula Q can be obtained.

An exemplary method for obtaining a compound of formula HH is shown in scheme O below:

wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formula (IIIa) and (IIIb).

Procedure O

Phenol FF (about 12mmol) was dissolved in concentrated sulfuric acid (about 10mL) at 0 ℃ and the resulting solution was cooled to a temperature of about-13 ℃ to about-15 ℃. About 1mL of 70% nitric acid was added to the resulting solution over about 30 minutes, and the resulting reaction mixture was stirred at a temperature of about-13 ℃ to about-15 ℃ for about 2 hours. The reaction mixture was then poured into ice water (about 100mL), neutralized with 5% -10% aqueous sodium hydroxide and extracted with about 50mL of chloroform. Chloroform was separated from the aqueous layer and removed under reduced pressure to give a residue which was purified by flash chromatography (silica gel column and chloroform eluent) to give a compound of formula GG. The compound of formula GG was dissolved in ethanol (about 50mL) and hydrogenated at room temperature for about 12 hours using 10% palladium on carbon as the catalyst. The catalyst was removed by filtration and the ethanol removed under reduced pressure to give a residue which was purified by flash chromatography (silica gel, eluting with 20: 1 dichloromethane: methanol) to give the compound of formula HH. The compounds of formula FF are commercially available or can be prepared by methods well known to those skilled in the art.

By reaction with the benzazolyl piperazine compounds of formula (Ia) and (Ib) shown above in scheme E (where x is 1, A is-C (O) -NR)₄-and R₄Is- (C)₁-C₆) Alkyl) with the benzoxazole piperazine compounds of the formulae (IIIa) and (IIIb) obtained as described above (where x is 1 and A is-C (O) -NR₄-and R₄is-H) in place of the benzoxazole piperazine compounds of the formulae (Ia) and (Ib) (wherein x is 1 and A is-C (O) -NR₄-and R₄is-H), benzoxazole piperazine compounds of the formulae (IIIa) and (IIIb) are obtained, wherein x is 1 and A is-C (O) -NR₄-and R₄Is- (C)₁-C₆) An alkyl group.

4.2.8 preparation of compounds in which x is 1 and A is-C (S) -NR₄A process for preparing benzoxazole piperazine compounds of formulae (IIIa) and (IIIb)

By reacting with the benzazolyl piperazine compounds described in scheme F above for obtaining the formula (Ia) and (Ib) (where x is 1 and A is-C, (S) -NR₄-and R₄In a similar manner to-H), but replacing the compound of formula C by a compound of formula Q, benzoxazole piperazine compounds of formulae (IIIa) and (IIIb) are obtained, wherein x is 1 and A is-C (S) -NR₄-and R₄is-H. The compounds of formula Q are obtainable as described above.

By reaction with the benzazolyl piperazine compounds of formula (Ia) and (Ib) shown above in scheme E (where x is 1, A is-C (O) -NR)₄-and R₄Is- (C) ₁-C₆) Alkyl) with the benzoxazole piperazine compounds of the formulae (IIIa) and (IIIb) obtained as described above (where x is 1 and A is-C (S) -NR₄-and R₄is-H) in place of the benzoxazole piperazine compounds of the formulae (Ia) and (Ib) (wherein x is 1 and A is-C (O) -NR₄-and R₄is-H), benzoxazole piperazine compounds of the formulae (IIIa) and (IIIb) are obtained, wherein x is 1, A is-C (S) -NR₄-and R₄Is- (C)₁-C₆) An alkyl group.

4.2.9 Process for preparing benzoxazole piperazine compounds of formula (IIIa) and (IIIb) wherein X is 0

The benzoxazole piperazine compounds of formulae (IIIa) and (IIIb) wherein X is 0 can be obtained by the method shown in the following scheme P.

Benzo of formulae (IIIa) and (IIIb)

Azole piperazine compound

Wherein Ar is₁、R₃、R₈、R₉And m is as defined above for the benzoxazole piperazine compounds of formulae (IIIa) and (IIIb).

Procedure P

The compound of formula S (about 15 to about 20mmol) and the compound of formula T (about 1 equivalent) are dissolved in ethanol (about 30 to about 40mL) and the resulting reaction mixture is heated at reflux temperature for about 5 h. The reaction mixture was concentrated under reduced pressure to give a residue, which was diluted with water (about 30mL) and acidified with acetic acid to a pH of about 6. The aqueous mixture was then extracted with ethyl acetate, the ethyl acetate (sodium sulfate) was dried and the solvent was removed under reduced pressure to give the compound of formula Y, which was used without further purification. The compound of formula Y (about 1mmol) and the compound of formula a (about 1 equivalent) are dissolved in toluene or p-xylene (about 0.5.mL to about 1mL) and the reaction mixture is heated in a sealed tube at a temperature of about 150 ℃ for about 24 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue obtained can be purified by flash chromatography (silica gel, 5: 95 methanol: DCM) to give the benzoxazole piperazine compounds of the formulae (IIIa) and (HIb) in which x is 0.

The compounds of formula S are commercially available or may be prepared by methods well known to those skilled in the art. An exemplary method for obtaining a compound of formula S is shown in scheme Q below:

wherein R is₈And R₉As defined above for the benzoxazole piperazine compounds of formula (IIIa) and (IIIb).

Procedure Q

Phenol II (about 12mmol) was dissolved in concentrated sulfuric acid (about 10mL) at 0 deg.C and the resulting solution was cooled to a temperature of about-13 deg.C to about-15 deg.C. About 1mL of 70% nitric acid was added to the resulting solution over about 30 minutes, and the resulting reaction mixture was stirred at a temperature of about-13 ℃ to about-15 ℃ for about 2 hours. The reaction mixture was then poured into ice water (about 100mL), neutralized with 5% -10% aqueous sodium hydroxide and extracted with about 50mL of chloroform. The chloroform was separated from the aqueous layer and removed under reduced pressure to give a residue which was purified by flash chromatography (silica gel column and chloroform eluent) to give the compound of formula JJ. The compound of formula JJ was dissolved in ethanol (about 50mL) and hydrogenated at room temperature for about 12 hours using 10% palladium on carbon as the catalyst. The catalyst was removed by filtration and the ethanol removed under reduced pressure to give a residue which was purified by flash chromatography (silica gel, eluting with 20: 1 dichloromethane: methanol) to give the compound of formula S. The compounds of formula S are commercially available or may be prepared by methods well known to those skilled in the art.

The compound of formula T is commercially available from Sigma-Aldrich, St.Louis, MO (www.sigma-aldrich.com).

The compounds of formula a may be obtained as described above.

Suitable aprotic organic solvents for the exemplary process include, but are not limited to, DCM, DMSO, chloroform, toluene, benzene, acetonitrile, carbon tetrachloride, pentane, hexane, rigorousin (ligroin) and diethyl ether. In one embodiment, the aprotic organic solvent is DCM.

Certain benzoxazole piperazine compounds may have one or more asymmetric centers and thus exist in different enantiomeric and diastereomeric forms. The benzoxazole piperazine compound may be in the form of optical isomers or diastereomers.

Accordingly, the present invention includes benzoxazole piperazine compounds in the form of optical isomers, diastereomers, and mixtures thereof (including racemic mixtures) and uses as described herein.

In addition, one or more hydrogen, carbon or other atoms of the benzoxazole piperazine compound may be substituted with an isotope of hydrogen, carbon or other atom. Such compounds encompassed by the present invention are useful as research and diagnostic tools in metabolic pharmacokinetic studies and in binding assay assays.

4.3 therapeutic uses of Benzoxazole piperazine Compounds

According to the present invention, the benzoxazole piperazine compound is administered to an animal in need of treatment or prevention of the following sputum diseases: pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression.

In one embodiment, an effective amount of a benzoxazole piperazine compound may be used to treat or prevent any disease that may be treated or prevented by inhibiting VR 1. Examples of diseases that may be treated or prevented by inhibition of VR1 include, but are not limited to, pain, UI, ulcers, IBD, and IBS.

In another embodiment, an effective amount of a benzoxazole piperazine compound may be used to treat or prevent any disease that may be treated or prevented by inhibiting mGluR 5. Examples of disorders that can be treated or prevented by inhibiting mGluR5 include, but are not limited to, pain, addiction disorders, parkinson's disease, parkinsonism, anxiety disorders, pruritis, and psychosis.

In another embodiment, an effective amount of a benzoxazole piperazine compound may be used to treat or prevent any disease that may be treated or prevented by inhibiting mGluR 1. Examples of diseases that can be treated or prevented by inhibiting mGluR1 include, but are not limited to, pain, VI, addiction, parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, seizure, pruritus, psychosis, cognitive disorders, memory deficits, restricted brain function, huntington's chorea, ALS, dementia, retinopathy, muscle spasm, migraine, emesis, movement disorders, and depression.

The benzoxazole piperazine compounds may be used for the treatment or prevention of acute or chronic pain. Examples of pain that can be treated or prevented with the benzoxazole piperazine compounds include, but are not limited to, cancer pain, central pain, labor pain, myocardial infarction pain, pancreatic pain, colic pain, post-operative pain, headache, muscle pain, pain associated with intensive care, joint pain, and pain associated with periodontal disease, including gingivitis and periodontitis.

The pain being treated or prevented may be associated with inflammation associated with inflammatory diseases, where inflammation occurs in body tissues, i.e. pain is produced, which may be a local inflammatory response and/or systemic inflammation. For example, the benzoxazole piperazine compounds are useful for treating or preventing pain associated with inflammatory diseases, including, but not limited to: organ transplant rejection; reoxygenation injury resulting from organ transplantation (see Grupp et al, J.mol, Cell Cardiol.31: 297-303(1999)), including, but not limited to, heart, lung, liver or kidney transplantation; chronic inflammatory diseases of the joints including arthritis, rheumatoid arthritis, osteoarthritis and bone diseases associated with increased bone resorption; inflammatory bowel diseases such as ileitis, ulcerative colitis, Barrett's syndrome and Crohn's disease; inflammatory lung diseases such as asthma, adult respiratory distress syndrome, and chronic obstructive respiratory disease; inflammatory diseases of the eye including corneal dystrophy, trachoma, onchocerciasis, uveitis, sympathetic ophthalmia, and endophthalmitis; chronic inflammatory diseases of the gums including gingivitis and periodontitis; pulmonary tuberculosis; -leprosy; inflammatory diseases of the kidney, including uremic complications, glomerulonephritis and renal disease; inflammatory diseases of the skin including sclerodermatitis, psoriasis and eczema; inflammatory diseases of the central nervous system, including demyelinating diseases of the chronic nervous system, multiple sclerosis, AIDS-related neurodegeneration and Alzheimer's disease, infectious meningitis, encephalomyelitis, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and viral or autoimmune encephalitis; autoimmune diseases, including type I and type II diabetes; diabetic complications, including, but not limited to, diabetic cataracts, glaucoma, retinopathy, nephropathy (such as microcolumnar and progressive diabetic nephropathy), polyneuropathy, mononeuropathy, autonomic neuropathy, foot gangrene, atherosclerotic coronary artery disease, peripheral arterial disease, nonketotic hyperglycemia-hyperosmolar coma (nonketotic-hyperosmolar coma), foot ulcers, joint disorders, and skin or mucosal complications (such as infection, tibial plaque (a shot), candida infection, or diabetic lipoid progressive necrosis); immune-complex-induced vasculitis nodosa and Systemic Lupus Erythematosus (SLE); inflammatory diseases of the heart, such as cardiomyopathy, ischemic heart disease, hypercholesterolemia, and atherosclerosis; and various other diseases that may have a significant inflammatory component, including pre-eclampsia, chronic liver failure, brain and spinal cord injury, and cancer. The benzoxazole piperazine compounds may also be used to inhibit, treat or prevent pain associated with inflammatory diseases, which may be, for example, systemic inflammation, such as gram-positive or gram-negative shock, hemorrhagic or anaphylactic shock, or shock due to cancer chemotherapy in response to pro-inflammatory cytokines, such as shock associated with pro-inflammatory cytokines. Such shock can result, for example, from administration of chemotherapeutic agents for the treatment of cancer.

The benzoxazole piperazine compounds may be used for the treatment or prevention of UI. Examples of UI that may be treated or prevented using the benzoxazole piperazine compounds include, but are not limited to, urge incontinence, stress incontinence, overflow incontinence, neurological incontinence, and total incontinence.

The benzoxazole piperazine compounds can be used for treating or preventing ulcers. Examples of ulcers that may be treated or prevented using benzoxazole piperazine compounds include, but are not limited to, duodenal ulcers, gastric ulcers, marginal ulcers, esophageal ulcers, or tension ulcers.

The benzoxazole piperazine compounds may be used in the treatment or prevention of IBD, including Crohn's disease and ulcerative colitis.

The benzoxazole piperazine compounds may be used for treating or preventing IBS. Examples of IBS that can be treated or prevented using benzoxazole piperazine compounds include, but are not limited to, spastic-colon-type IBS and constipation-predominant IBS.

The benzoxazole piperazine compounds may be used for the treatment or prevention of addiction disorders including, but not limited to, eating disorders, impulse-control disorders, alcohol-related disorders, nicotine-related disorders, amphetamine-related disorders, cannabis-related disorders, cocaine-related disorders, hallucinogen-related disorders, inhalant (inhalant) -related disorders, and opioid-related disorders, all of which are listed below in further detail.

Eating disorders include, but are not limited to, non-scavenging (Nonpurging Type) bulimia nervosa; (purging type) neurogenic bulimia; anorexia; and non-specific (NOS) eating disorders.

Impulse control disorders include, but are not limited to, intermittent explosive neurological disorders, kleptomania, pyromania, pathological gambling, trichotillomania, and non-specific (NOS) impulse control disorders.

Alcohol-related disorders include, but are not limited to, alcohol-induced psychosis with delusions, alcohol abuse, alcoholism, alcohol withdrawal, confusion due to alcoholism, confusion due to alcohol withdrawal, alcohol-induced intractable dementia, alcohol-induced persistent amnesia, alcohol dependence, alcohol-induced psychosis with hallucinations, alcohol-induced mood disorder, alcohol-induced anxiety disorder, alcohol-induced sexual dysfunction, alcohol-induced sleep disorder, alcohol-induced non-specific (NOS) disease, alcoholism, and alcohol withdrawal symptoms.

Nicotine-related disorders include, but are not limited to, nicotine dependence, nicotine withdrawal symptoms, and nicotine-related non-specific (NOS) disorders.

Amphetamine-related disorders include, but are not limited to, amphetamine dependence, amphetamine abuse, amphetamine intoxication, amphetamine withdrawal symptoms, amphetamine intoxication delirium, amphetamine-induced psychosis with delusions, amphetamine-induced psychosis with hallucinations, amphetamine-induced mood disorders, amphetamine-induced anxiety disorders, amphetamine-induced sexual dysfunction, amphetamine-induced sleep disorders, amphetamine-related non-characterized (NOS) disease, amphetamine intoxication, and amphetamine withdrawal symptoms.

Cannabis-related disorders include, but are not limited to, cannabis dependence, cannabis abuse, cannabis intoxication delirium, cannabis-induced psychosis with delusions, cannabis-induced psychosis with hallucinations, cannabis-induced anxiety disorder, cannabis-related non-specific (NOS) disease, and cannabis intoxication.

Cocaine-related disorders include, but are not limited to, cocaine dependence, cocaine abuse, cocaine intoxication, cocaine withdrawal symptoms, cocaine intoxication delirium, cocaine-induced psychosis with delusions, cocaine-induced psychosis with hallucinations, cocaine-induced mood disorders, cocaine-induced anxiety disorders, cocaine-induced sexual dysfunction, cocaine-induced sleep disorders, cocaine-related non-specific (NOS) diseases, cocaine intoxication, and cocaine withdrawal symptoms.

Hallucinogenic agent-associated disorders include, but are not limited to, hallucinogenic agent dependence, hallucinogenic agent abuse, hallucinogenic agent intoxication, hallucinogenic agent withdrawal symptoms, hallucinogenic agent intoxication delirium, hallucinogenic agent-induced psychosis with delusions, hallucinogenic agent-induced psychosis with hallucinations, hallucinogenic agent-induced mood disorder, hallucinogenic agent-induced anxiety disorder, hallucinogenic agent-induced sexual dysfunction, hallucinogenic agent-induced sleep disorder, hallucinogenic agent-associated non-characterized (NOS) disease, hallucinogenic agent intoxication, and hallucinogenic agent persistent perceptual disorder (flashbacs).

Inhalant-related disorders include, but are not limited to, inhalant-dependent symptoms, inhalant abuse, inhalant intoxication delirium, inhalant-induced psychosis with delusions, inhalant-induced psychosis with hallucinations, inhalant-induced anxiety disorder, inhalant-related non-specific (NOS) disease, and inhalant intoxication.

Opioid-related disorders include, but are not limited to, opioid-dependent symptoms, opioid abuse, opioid intoxication delirium, opioid-induced psychosis with delusions, opioid-induced psychosis with hallucinations, opioid-induced anxiety disorder, opioid-related non-specific (NOS) disorder, opioid intoxication, and opioid withdrawal symptoms.

The benzoxazole piperazine compounds may be used to treat or prevent parkinson's disease and parkinsonism and symptoms associated with parkinson's disease and parkinsonism, including, but not limited to, bradykinesia, muscle stiffness, resting tremor, and impaired postural balance.

The benzoxazole piperazine compounds may be used to treat or prevent generalized anxiety disorder or severe anxiety disorder, as well as symptoms associated with anxiety disorders, including but not limited to restlessness; tension; tachycardia is treated; dyspnea; depression, including chronic "neuropathic" depression; panic disorder; agoraphobia and other specific phobias; eating disorders; and personality disorders.

The benzoxazole piperazine compounds may be used in the treatment or prevention of epilepsy, including, but not limited to, partial epilepsy, generalized epilepsy, and epilepsy-related conditions, including, but not limited to, simple partial seizures, jackson's seizures, generalized partial (psychomotor) seizures, convulsive seizures (severe (grand mal) or tonic-clonic seizures), mild (petit mal) (unconscious) seizures, and status epilepticus.

The benzoxazole piperazine compounds may be used to treat or prevent stroke, including but not limited to, localized hemorrhagic stroke and hemorrhagic stroke.

The benzoxazole piperazine compounds are useful for treating or preventing seizure episodes, including but not limited to infant seizure, febrile seizure and epileptic seizure.

The benzoxazole piperazine compounds are useful for treating or preventing pruritus, including but not limited to pruritus due to dry skin, scabies, dermatitis, herpetiform rash, atopic dermatitis, vulvar pruritus (pruritus vulvae et ani), miliaria, insect bites, pediculosis, contact dermatitis, drug reactions, urticaria gravidarum-like rash, psoriasis, lichen planus, lichen simplex chronicus, exfoliative dermatitis, folliculitis, bullous pemphigoid, or cellophane dermatitis.

The benzoxazole piperazine compounds are useful for treating or preventing psychosis, including, but not limited to, schizophrenia, including delusional, adolescent, or disorganized schizophrenia, catatonic schizophrenia, mixed schizophrenia, schizophrenic or anorgasmic (deficit) subtype schizophrenia, and active (non-deficit) schizophrenia; delusional disorders including erogenous subtype delusional disorder, exaggerating subtype delusional disorder, jealoussubtype delusional disorder, abusive subtype delusional disorder, and somatic subtype delusional disorder; and simple psychosis.

The benzoxazole piperazine compounds are useful for treating or preventing cognitive disorders, including but not limited to delirium and dementia, such as multi-infarct dementia, dementia pugilistica, dementia caused by AIDS, and dementia caused by alzheimer's disease.

The benzoxazole piperazine compounds are useful for treating or preventing memory deficits, including but not limited to, zero-dispersion memory deficits and zero-dispersion psychotoma.

The benzoxazole piperazine compounds are useful for treating or preventing restricted brain function, including but not limited to restricted brain function caused by surgery or organ transplantation, restricted blood supply to the brain, spinal cord injury, head injury, hypoxia, cardiac arrest, or hypoglycemia.

The benzoxazole piperazine compound can be used for treating or preventing Huntington chorea.

The benzoxazole piperazine compounds are useful for treating or preventing ALS.

The benzoxazole piperazine compounds are useful for treating or preventing retinopathies, including but not limited to, arteriosclerotic retinopathy, diabetic arteriosclerotic retinopathy, hypertensive retinopathy, non-proliferative retinopathy, and proliferative retinopathy.

The benzoxazole piperazine compounds are useful for treating or preventing muscle spasms.

The benzoxazole piperazine compounds are useful for treating or preventing migraine, including, but not limited to, migraine without aura ("common migraine"), migraine with aura ("classical migraine"), migraine without whole headaches, basal migraine, familial hemiplegic migraine, migraine infarct, and migraine with long-term aura.

The benzoxazole piperazine compounds are useful for treating or preventing emesis, including but not limited to nausea, feeling of vomiting (retching) and regurgitation.

The benzoxazole piperazine compounds are useful for treating or preventing dyskinesias, including but not limited to tardive dyskinesia and transport bile dyskinesia.

The benzoxazole piperazine compounds are useful for treating or preventing depression, including but not limited to major depression and bipolar disorder.

Applicants believe that the benzoxazole piperazine compounds are antagonists of VR 1.

The invention also relates to a method of inhibiting the function of VR1 in a cell, the method comprising contacting a cell capable of expressing VR1 with an effective amount of a benzoxazole piperazine compound. The method can be used in vitro, for example, in assays that select for cells that express VR1, and thus, can be used in partial assays to screen for compounds useful in treating or preventing pain, UI, ulcers, IBD, or IBS. In one embodiment, the method is also used to inhibit the function of VR1 in cells in an animal, human, or other human by contacting cells of the animal with an effective amount of a benzoxazole piperazine compound. In one embodiment, the method is for treating or preventing pain in an animal. In another embodiment, the method is for treating or preventing UI in an animal. In another embodiment, the method is for treating or preventing an ulcer in an animal. In another embodiment, the method is for treating or preventing IBD in an animal. In another embodiment, the method is for treating or preventing IBS in an animal.

Examples of tissues comprising cells capable of expressing VR1 include, but are not limited to, neuronal, brain, kidney, urothelium, and bladder tissues. Methods for determining cells capable of expressing VR1 are well known in the art.

Applicants believe that the benzoxazole piperazine compounds are antagonists of mGluR 5.

The invention also relates to a method of inhibiting mGluR5 function in a cell, the method comprising contacting a cell capable of expressing mGluR5 with an amount of a benzoxazole piperazine compound effective to inhibit mGluR5 function in the cell. The method can be used, for example, in assays that select for cells that express mGluR5 in vitro, and thus, can be used in partial assays for selecting compounds useful for treating or preventing pain, addiction, parkinson's disease, parkinson's syndrome, anxiety, pruritis, or psychosis. In one embodiment, the method is also used to inhibit mGluR5 function in cells in animals, humans by contacting cells of the animal with an effective amount of a benzoxazole piperazine compound that inhibits mGluR5 function in the cell. In one embodiment, the method is for treating or preventing pain in an animal in need thereof. In another embodiment, the method is for treating or preventing an addictive disorder in an animal in need thereof. In another embodiment, the method is for treating or preventing parkinson's disease in an animal in need thereof. In another embodiment, the method is for treating or preventing parkinsonism in an animal in need thereof. In another embodiment, the method is for treating or preventing anxiety symptoms in an animal in need thereof. In another embodiment, the method is for treating or preventing pruritus in an animal in need thereof. In another embodiment, the method is for treating or preventing psychosis in an animal in need thereof.

Examples of cells capable of expressing mGluR5 are central nervous system neurons and glial cells, especially the brain, and especially the nuclei of the sit (nuclei accumbens). Methods for determining cells expressing mGluR5 are well known in the art.

Applicants believe that the benzoxazole piperazine compounds are antagonists of mGluR 1.

The invention also relates to a method of inhibiting mGluR1 function in a cell, the method comprising contacting a cell capable of expressing mGluR1 with an amount of a benzoxazole piperazine compound effective to inhibit mGluR1 function in the cell. This method can be used, for example, in assays for selecting cells that express mGluR1 in vitro, and thus, for selecting compounds useful for treating or preventing: pain, UI, addiction, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, seizures, pruritus, psychosis, cognitive disorders, memory deficits, restricted retinopathy, chronic chorea, ALS, dementia, retinopathy, muscle spasms, migraine, emesis, movement disorders or depression. In one embodiment, the method is also used to inhibit mGluR1 function in cells in animals, humans by contacting cells of the animal with an effective amount of a benzoxazole piperazine compound that inhibits mGluR1 function in the cell. In one embodiment, the method is for treating or preventing pain in an animal in need thereof. In another embodiment, the method is for treating or preventing UI in an animal in need thereof. In another embodiment, the method is for treating or preventing an addictive disorder in an animal in need thereof. In another embodiment, the method is for treating or preventing parkinson's disease in an animal in need thereof. In another embodiment, the method is for treating or preventing parkinsonism in an animal in need thereof. In another embodiment, the method is for treating or preventing anxiety in an animal in need thereof. In another embodiment, the method is for treating or preventing epilepsy in an animal in need thereof. In another embodiment, the method is for treating or preventing stroke in an animal in need thereof. In another embodiment, the method is for treating or preventing seizures in an animal in need thereof. In another embodiment, the method is for treating or preventing pruritus in an animal in need thereof. In another embodiment, the method is for treating or preventing psychosis in an animal in need thereof. In another embodiment, the method is for treating or cognitive disorders in an animal in need thereof. In another embodiment, the method is for treating or preventing memory loss in an animal in need thereof. In another embodiment, the method is for treating or preventing restricted brain function in an animal in need thereof. In another embodiment, the method is for treating or preventing huntington's chorea in an animal in need thereof. In another embodiment, the method is for treating or preventing ALS in an animal in need thereof. In another embodiment, the method is for treating or preventing dementia in an animal in need thereof. In another embodiment, the method is for treating or preventing retinopathy in an animal in need thereof. In another embodiment, the method is for treating or preventing a muscle spasm in an animal in need thereof. In another embodiment, the method is for treating or preventing migraine in an animal in need thereof. In another embodiment, the method is for treating or preventing emesis in an animal in need thereof. In another embodiment, the method is for treating or preventing a movement disorder in an animal in need thereof. In another embodiment, the method is for treating or preventing depression in an animal in need thereof.

Examples of cells capable of expressing mGluR1 include, but are not limited to, purkinje neuronal cells of the cerebellum, purkinje cell bodies (punctate), cerebellar spine cells; olfactory neuro-glomerular neurons and neurotropic cells; surface cells of the cerebral cortex; hippocampal isthmus cells; thalamic cells; a cumulus cell; and spinal trigeminal nerve cells. Methods for determining cells capable of expressing mGluR1 are well known in the art.

4.3.1 methods of therapeutic/prophylactic administration and compositions of the invention

Due to their activity, said benzoxazole piperazine compounds are advantageously used in veterinary and human medicine. As described above, the benzoxazole piperazine compounds are used for treating or preventing pain, UI, ulcers, IBD, IBS, addiction, parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, seizures, pruritis, psychosis, cognitive disorders, memory deficits, restricted brain function, huntington's chorea, ALS, dementia, retinopathy, muscle spasm, migraine, emesis, dyskinesia, or depression in an animal in need thereof.

When administered to an animal, the benzoxazole piperazine compound can be administered as a component of a composition that includes a pharmaceutically acceptable carrier. The composition of the present invention, which comprises the benzoxazole piperazine compound, may be administered orally. The benzoxazole piperazine compounds of the present invention may also be administered by any other conventional route, e.g., via infusion or bolus injection, absorption via epithelial or mucocutaneous intima (e.g., oral, rectal, and intestinal mucosa, etc.), and may be administered with another bioactive agent. Administration may be systemic or local. Various delivery systems are known, for example, encapsulation in liposomes, microparticles, microcapsules, capsules, and the like, and can be used to administer the benzoxazole piperazine compounds.

Methods of administration include, but are not limited to, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, oral, sublingual, intracerebral, intravaginal, transdermal, rectal, inhalation, or topical (particularly otic, nasal, ocular, or cutaneous) administration. The mode of administration should be considered by the physician. In most cases, administration will result in the release of the benzoxazole piperazine compound into the bloodstream.

In particular embodiments, topical administration of the benzoxazole piperazine compound may be desirable. This can be achieved by: for example, but not by way of limitation, by local infusion during surgery, topical application (e.g., for use with a wound dressing after surgery), by injection, by intubation, by suppository or enema, or by implantation, the implant being a porous, non-porous, or gelatinous material, including membranes, such as sialastic films or fibers.

In certain embodiments, it may be desirable to introduce the benzoxazole piperazine compound into the central nervous system or the gastrointestinal tract by any suitable route, including intraventricular, intrathecal and epidural injection and enema. Intraventricular injections may be conveniently performed by inserting a catheter, for example, attached to a depot (e.g., an Ommaya depot) within the ventricle.

Pulmonary administration can also be employed, for example, by use of an inhaler or nebulizer, as well as formulations containing a smoke nebulizer, or by infusion with fluorocarbon or synthetic pulmonary surfactants. In certain embodiments, the benzoxazole piperazine compounds may be formulated as suppositories with common binders and excipients (such as triglycerides).

In another embodiment, the benzoxazole piperazine compound can be delivered in a vehicle, particularly a liposome (see Langer, Science 249: 1527-1533(1990) and Treat et al, lipids in the Therapy of infection Disease and Cancer 317-327 and 353-365 (1989)).

In another embodiment, the benzoxazole piperazine compound can be delivered in a controlled or sustained Release system (see, e.g., Goodson, in Medical Applications of controlled Release, supra, vol.2, pp.115-138 (1984)). Langer, Science 249: 1527 and 1533 (1990). In one embodiment, pumps may be used (Langer, Science 249: 1527-. In another embodiment, polymeric materials may be used (see medical applications of Controlled Release (Langer and Wise, eds., 1974); Controlled Drug Bioavailability, Drug Product Design and Performance (Smolen and Ball eds., 1984); Ranger and Peppas, J.Macromol, Sci.Rev.Macromol. chem.23: 61 (1983); Levy et al, Science 228: 190 (1985); During et al, Ann, Neurol.25: 351 (1989); and Howard et al, J.Neurosurg.71: 105 (1989)). In another embodiment, a controlled or sustained release system may be placed in the vicinity of the target of the benzoxazole piperazine compound, e.g., at the spine, brain, or gastrointestinal tract, thus requiring only a fraction of the systemic dose.

In one embodiment, the pharmaceutically acceptable carrier is an excipient. Such pharmaceutical excipients may be liquids, such as water and oils, including petroleum, animal oils, vegetable oils, or oils of synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, and the like. The pharmaceutically acceptable excipient may be saline, gum arabic, gelatin, starch paste, talc, keratin, colloidal silica, urea, etc. In addition, adjuvants, stabilizers, thickeners, lubricants and colorants may be used. In one embodiment, the pharmaceutically acceptable excipient should be sterile when administered to an animal. Water is a particularly useful excipient when the benzoxazole piperazine compound is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions may also be employed as liquid excipients, particularly for injectable solutions. Suitable pharmaceutical excipients also include starch, glucose, lactose, sucrose, gelatin, maltose, rice starch, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene glycol, ethylene glycol, water, ethanol and the like. The compositions of the invention may also contain minor amounts of wetting or emulsifying agents or pH buffering agents, if desired.

The compositions of the present invention may take the form of solutions, suspensions, emulsions, tablets, pills, pellets, capsules containing liquids, powders, sustained release formulations, suppositories, emulsions, aerosols, sprays, suspensions or any other form suitable for use. In one embodiment, the composition is in the form of a capsule (see, e.g., U.S. Pat. No. 5,698,155). Other examples of suitable pharmaceutical excipients are described in Remington's pharmaceutical sciences 1447-.

In one embodiment, the benzoxazole piperazine compound is formulated in a composition suitable for oral administration to a human according to conventional methods. Compositions for oral delivery may be, for example, tablets, troches, aqueous or oily suspensions, granules, powders, emulsions, capsules, syrups or elixirs. To obtain a pharmaceutically palatable preparation, the compositions for oral administration may contain one or more excipients, for example, sweetening agents, such as fructose, aspartame or saccharin; flavoring agents, such as peppermint, oil of wintergreen, or cherry; a colorant; and a preservative. In addition, when the composition is in the form of tablets or pills, the composition may be coated to delay disintegration and absorption in the gastrointestinal tract, thereby providing a sustained action over a prolonged period of time. Selectively permeable membranes surrounding an osmotically active driving compound are also suitable for orally administered compositions. In these latter plateau curves, liquid from the environment surrounding the capsule is infiltrated by the driver compound, which swells to displace the drug or drug composition through the void. These delivery plateau profiles can provide a substantially zero order release profile relative to the peak profile of the immediate release formulation. Time delay materials such as glyceryl monostearate or glyceryl stearate may also be used. Oral compositions may include standard excipients such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose and magnesium carbonate. In one embodiment, the excipient is pharmaceutical grade.

In another embodiment, the benzoxazole piperazine compound may be formulated for intravenous administration. Generally, compositions for intravenous administration include sterile isotonic aqueous buffers. If necessary, the composition may also include a solubilizing agent. Compositions for intravenous administration may optionally include a local anesthetic, such as lidocaine to reduce pain at the site of injection. Generally, the ingredients will be presented separately or together in unit dosage form, e.g., as a lyophilized powder or water-free concentrate in a sealed container such as an ampoule or sachet indicating the amount of active agent. When the benzoxazole piperazine compounds are administered by infusion, they may be dispensed, for example, with an infusion bottle containing sterile pharmaceutical grade water for injection or saline. When the benzoxazole piperazine compound is administered by injection, an ampoule of sterile water for injection or saline may be provided so that the ingredients may be mixed before administration.

The benzoxazole piperazine compounds may be administered in a controlled or sustained release manner or by delivery devices well known to those of ordinary skill in the art. Examples include, but are not limited to, those described in U.S. Pat. nos. 3,845,770; 3,916,899; 3,536,809, respectively; 3,598,123, respectively; 4,008,719, respectively; 5,674,533, respectively; 5,059,595, respectively; 5,591,767, respectively; 5,120,548, respectively; 5,073,543, respectively; 5,639,476, respectively; 5,354,556, respectively; and 5,733,566, each of which is incorporated herein by reference. Such dosage forms may be employed to provide controlled or sustained release of one or more active ingredients, employing, for example, hydroxypropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems, multilayer coatings, microparticles, liposomes, microspheres, or combinations thereof, to provide the desired release profile in varying proportions. Suitable controlled or sustained release formulations (including those described herein) well known to those of ordinary skill in the art can be readily selected for use in accordance with the active ingredients of the present invention. Thus, the present invention encompasses single unit dosage forms suitable for oral administration, such as, but not limited to, tablets, capsules, caplets (gelcaps), and caplets, suitable for controlled or sustained release.

Controlled or sustained release pharmaceutical compositions may have a common goal of improved drug therapy compared to corresponding compositions that are not controlled or sustained released. In one embodiment, the controlled or sustained release composition comprises a minimal amount of a benzoxazole piperazine compound to treat or control a disease with a minimal number of administrations. Advantages of controlled or sustained release compositions include prolonged drug activity, reduced dosing frequency and increased patient compliance. In addition, the controlled or sustained release composition may advantageously affect the time of onset of action or other characteristics, such as blood levels of the benzoxazole piperazine compound, and thus may reduce the occurrence of adverse side effects.

The controlled or sustained release composition may initially release an amount of the benzoxazole piperazine compound that can rapidly produce the desired therapeutic or prophylactic effect, and then gradually and continuously release other amounts of the benzoxazole piperazine compound over an extended period of time at a level that maintains the therapeutic or prophylactic effect. To maintain a constant level of the benzoxazole-based piperazine compound in the body, the benzoxazole-based piperazine compound may be released from the dosage form at a rate that replaces the amount of benzoxazole-based piperazine compound that is metabolized and excreted from the body. Controlled or sustained release of the active ingredient can be affected by a variety of conditions, including but not limited to changes in pH, changes in temperature, changes in enzyme concentration or availability, changes in water concentration or availability, or changes in other physiological conditions or compounds.

The amount of the benzoxazole piperazine compound effective to treat or prevent the following diseases or symptoms can be determined by standard clinical techniques: pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression. In addition, in vitro or in vivo assays may optionally be employed to help determine the optimal dosage range. The precise dose to be employed will also depend on the route of administration and the severity of the condition being treated and should be determined at the discretion of the attendant physician and in the individual patient's circumstances, e.g. in open clinical studies. However, suitable effective dosages range from about 10 micrograms to about 2500 milligrams about every 4 hours, although they are typically about 100mg or less. In one embodiment, an effective dose ranges from about 0.01 mg to about 100mg of the benzoxazole piperazine compound about every 4 hours, in another embodiment from about 0.020 mg to about 50 mg about every 4 hours, and in yet another embodiment from about 0.025 mg to about 20 mg about every 4 hours. Effective dosages as described herein refer to the total amount administered; that is, if more than one benzoxazole piperazine compound is administered, the effective dose corresponds to the total amount administered.

When a cell capable of expressing VR1, mGluR5, or mGluR1 is contacted with a benzoxazole piperazine compound in vitro, an amount effective to inhibit the function of the receptor in the cell will generally range from about 0.01 μ g/L to about 5mg/L, in one embodiment from about 0.01 μ g/L to about 2.5mg/L, in another embodiment from about 0.01 μ g/L to about 0.5mg/L, and in another embodiment, from about 0.01 μ g/L to about 0.25mg/L of a solution or suspension of a pharmaceutically acceptable carrier or excipient. In one embodiment, the volume of the solution or suspension is from about 1 μ L to about 1 mL. In another embodiment, the volume of the solution or suspension is about 200 μ L.

When a cell capable of expressing VR1, mGluR5, or mGluR1 is contacted with a benzoxazole piperazine compound in vivo, an amount effective to inhibit the function of the receptor in the cell will typically be in the range of about 0.01mg to about 100mg/kg body weight per day, in one embodiment in the range of about 0.1mg to about 50mg/kg body weight per day, and in another embodiment in the range of about 1mg to about 20mg/kg body weight per day.

The desired therapeutic or prophylactic activity of the benzoxazole piperazine compounds can be determined in vitro or in vivo prior to use in humans. Animal model systems can be used to demonstrate safety and efficacy.

The methods of the invention for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal in need thereof can further comprise administering an additional therapeutic agent to the animal being treated with the benzoxazole piperazine compound. In one embodiment, the additional therapeutic agent is administered in an effective amount.

The methods of the invention for inhibiting VR1 function in a cell capable of expressing VR1 can further comprise contacting the cell with an effective amount of an additional therapeutic agent.

The methods of the invention for inhibiting mGluR5 function in a cell capable of expressing mGluR5 can further comprise contacting the cell with an effective amount of an additional therapeutic agent.

The methods of the invention for inhibiting mGluR1 function in a cell capable of expressing mGluR1 can further comprise contacting the cell with an effective amount of an additional therapeutic agent.

Such other therapeutic agents include, but are not limited to, opioid agonists, non-opioid analgesics, non-steroidal anti-inflammatory agents, anti-migraine agents, COX-II inhibitors, antiemetics, beta-adrenergic blockers, anticonvulsants, antidepressants, Ca ²⁺-a channel blocker,An anti-cancer agent, a drug for treating or preventing UI, a drug for treating or preventing ulcer, a drug for treating or preventing IBD, a drug for treating or preventing IBS, a drug for treating addiction disorders, a drug for treating Parkinson's disease and Parkinson's syndrome, a drug for treating anxiety, a drug for treating epileptic seizures, a drug for treating stroke, a drug for treating epileptic seizures, a drug for treating pruritis, a drug for treating psychosis, a drug for treating chronic chorea, a drug for treating ALS, a drug for treating cognitive impairment, a drug for treating migraine, a drug for treating emesis, a drug for treating dyskinesia or for treating depression, and mixtures thereof.

Effective amounts of other therapeutic agents are well known to those skilled in the art. However, determining the optimal effective amount range for other therapeutic agents is well within the purview of the skilled artisan. In one embodiment of the invention, the effective amount of the benzoxazole piperazine compound when administered to an animal is less than the effective amount when administered without another therapeutic agent. In this context, it is believed, without being bound by theory, that the benzoxazole piperazine compound and the other therapeutic agent act synergistically to treat or prevent pain, UI, an ulcer, IBD, IBS, an addiction, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression.

Examples of useful opioid agonists include, but are not limited to, alfentanil, allylprocaine, alpha-Prime, anileridine, benzylmorphine, benzonitrile, buprenorphine, butorphanol, lonicerazine, codeine, desomorphine, dextromoramide, dezocine, dinonylpropylamine, diamorphine (diamorphine), dihydrocodeine, dihydromorphine, dextromethorphan, dimethiophenecrotylamine, meperidine, dipiperazone, etazocine, eheptazine, ethylmethylthiophencrotamine, ethylmorphine, Etheniximazine, fentanyl, heroin, hydrocodone, hydromorphine, hydroxyperidine, isometholone, Ketomidone, levorphanol, fentanyl, meperidine, metadoxine, metazosine, methadone, morphine, mupirorphine, buprenorphine, levorphanol, meperidine, morphine, meperidine, nalorphine, naline, nalorphine, levorphanol, meperidine, normethadone, nalorphine, normorphine, nopiperone, opium, oxycodone, oxymorphone, opiate alkaloids, pentazocine, phenomenadione, fenorphane, phenazocine, phenperidine, piminodine, pimonitine, pramipexole, meperidine, propiverine, propiram, propoxyphene, sufentanil, tilidine, tramadol, pharmaceutically acceptable salts thereof, and mixtures thereof.

In certain embodiments, the opioid agonist is selected from codeine, hydromorphone, hydrocodone, oxycodone, dihydrocodeine, dihydromorphine, morphine, tramadol, oxymorphone, pharmaceutically acceptable salts thereof, and mixtures thereof.

Examples of useful non-opioid analgesics include non-steroidal anti-inflammatory drugs such as aspirin, ibuprofen, diclofenac, naproxen, benzeneLoxfen, flurbiprofen, fenoprofen, flubufen, ketoprofen, indoprofen, Piroprofen, carprofen, oxaprozin, Pramoprofen, muroprofen, trioxaprofen, suprofen, aminoprofen (aminoprofen), tiaprofenic acid, fluprofen, bucloxic acid, indomethacin, sulindac, tolmetin, zomepirac, thiofenac, zidometacin, acemetacin, fentiazac, clidanac, oxapinic, mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid, tolfenamic acid, diflunisal, flufenisal, piroxicam, sudoxicam, isoxicam, and pharmaceutically acceptable salts and mixtures thereof. Other suitable non-opioid analgesics include, but are not limited to, the following chemical analgesics, antipyretics, non-steroidal anti-inflammatory drugs: salicylic acid derivatives including aspirin, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, sulfosalicylic acid, and sulfasalazine Aminopyridine and olsalazine; para-aminophenol derivatives including acetaminophen and phenacetin; indoles and indene acetic acids including indomethacin, sulindac, and etodolac; heteroaryl acetic acids including tolmetin, diclofenac, and ketorolac; anthranilic acids (fenamates) including mefenamic acid and meclofenamic acid; enolic acids, including oxicams (piroxicam, tenoxicam) and pyrazolidinediones (phenylbutazone, oxyphenthartazone); and alkylketones (alkanones), including nabumetone. See Paul A. Insel, equivalent-inflammatory and Anti-inflammatory Agents and drugs injected in the Treatment of Gout, in Goodman for a more detailed description of NSAIDs.&Gilman's the pharmacological Basis of Therapeutics 617-57 (edited by Perry B. Molinhoff and Raymond W. Ruddon, 9 th edition, 1996) and Glen R. Hanson, Analgesic, antipyrotic and Anti-inflammatory Drugs in Remington: the Science and practice of Pharmacy Vol II 1196-1221(A.R. Gennaro, eds., 9 th edition, 1995), which is incorporated herein in its entirety by reference.

Examples of useful Cox-II inhibitors and 5-lipoxygenase inhibitors, and combinations thereof, are described in U.S. patent No.6,136,839, which is incorporated herein by reference in its entirety. Examples of useful Cox-II inhibitors include, but are not limited to, rofecoxib and celecoxib.

Examples of useful anti-migraine agents include, but are not limited to, apremide, dihydroergotamine, dolasetron, ergocornine, ergoisoconitine, ergopeptine, ergot, ergotamine, flumetrenone acetate, xylazine, lisuride, lomerizine, mexican, oxicolone, benzthiadine, and mixtures thereof.

The other therapeutic agent may also be a drug that may be used to reduce any potential side effects of a benzoxazole piperazine compound. For example, the other therapeutic agent may be an antiemetic agent. Examples of useful antiemetics include, but are not limited to, metoclopramide, domperidone, prochlorperazine, promethazine, chlorpromazine, trimethobenzamide, ondansetron, granisetron, hydroxyzine, acetylleucine, monoethanolamine, aripride, azasetron, benzquinamine, theophylline, brompride, buclizine, clopride, cyclizine, dimenhydrinate, diphenidol, dolasetron, meclizine, methadol, metopimazine, cannabirone, oxypendyl, pipamazine, scopolamine, sulpiride, tetrahydrocannabinol, thiethylperazine, thioproperazine, tropisetron, and mixtures thereof.

Examples of useful beta-adrenergic blockers include, but are not limited to, acebutolol, alprenolol, amotinolol, atenolol, benfuralol, betaxolol, bevantolol, bisoprolol, bopindolol, bucindolol, bufalol, bucindolol hydrochloride, bufalol, carpiprolol, carteolol, carvedilol, celiprolol, seliprolol, loralol, delaiprolol, epalol, esmolol, indanolol, labetalol, levobunolol, mepindolol, metipranolol, metoprolol, moprolol, nadolol, nafamoxolol, nebivolol, nifedilol, oxyphenalol, penbutolol, pindolol, propranolol, sotalol, tioxolol, atenolol, propranolol, bucindolol, bucindo, Talinolol, terbalol, tiliolol, timolol, toliprolol, and schizalol.

Examples of useful anticonvulsants include, but are not limited to, acetophenylbutamide, abuntoin, alodione, aminoglutethimide, gamma-aminobutyric acid, phenlactamide, becloramine, braurethan, calcium bromide, carbamazepine, cinnamylamine, clomeprazole, clonazepam, decyloxamide, dioxazadione, dimedone, doxenitrin, etabitol, ethazamide, ethosuximide, ethosuximin, felbamate, diethylsulfolane, gabapentin, 5-hydroxytryptamine, lamotrigine, magnesium bromide, magnesium sulfate, mefentol, mebendatol, methamphetamine, metin, methylsuccinamide, 5-methyl-5- (3-phenanthryl) -hydantoin, 3-methyl-5-phenylhydantoin, noscapine, nimetazepam, nitrazepam, oxcarbazepine, methadone, phenylacetylurea, Fenoxabel, phenylbutyluride, phenobarbital, phensuximide, phenobarbital, phenytoin sodium, potassium bromide, pregabaline, primidone, progosamide, sodium bromide, solanum, strontium bromide, succinofir, suthiazide, tetritytoin, tiagabine, topiramate, trimethadione, valproic acid, valproate, vigabatrin, and zonisamide.

Examples of useful antidepressants include, but are not limited to, benedaline, caroxazone, citalopram, dimetaxane, fencamine, indamine, indenolazine hydrochloride, nefopam, nomifensine, hydroxytryptophan, oxypertine, paroxetine, sertraline, fenthiolone, trazodone, benzoylprocarbazine, iprochlorhydrazine, isoniazid, nimoramide, otamoxine, phenelzine, cotinine, rolipram, maprotiline, metrexindole, mianserin, mirtazapine (mirtazepine), aclzolam, amitriptyline, oxoamitriptyline, amoxapine, desipramine, butraline, clomipramine, dememipramine, desipramine, dibenzapine, dothiepin, doxepine, fluazidine, imipramine, doxicapridine, doxifenpine, imipramine, doxicapridine, doxifenproxypromine, imipramine, nortriptyline, opipramol, pizotifen, propiopipine, protriptyline, quinupramine, tianeptine, trimipramine, acloninib, benactyzine, bupropion, butacetin, disoxaudine, duloxetine, etoperidone, febuxostat, femoxetine, fenglutarol, fluoxetine, fluvoxamine, hematoporphyrin, hypericin, levofenfluramine, memaxamine, milnacipran, moclobemide, nefazodone, oxafluocinolone, pirilarine, protriptan, piramine succinate, ritanserin, rocyline, rubidium chloride, sulpiride, duloxetine, toprazone, tolfenacin, toloxanone, tranylcypromine, L-tryptophan, tamarine, vilazone, and mezzidine.

Useful Ca²⁺Examples of-channel blockers include, but are not limited to, bepridil, clentriptan, diltiazem, fendilin,Gallopamil, mibefradil, prenylamine, semodil, terodiline, verapamil, amlodipine, aranidipine, barnidipine, benidipine, cilnidipine, efonidipine, elidipine, felodipine, isradipine, lacidipine, lercanidipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, cinnarizine, flunarizine, lidofloxacin, lomerizine, bencyclane, etaphenone, pantofalong, and perhexiline.

Examples of useful anticancer agents include, but are not limited to, acivicin, aclarubicin, alcodazole hydrochloride, aclopram, aldeskin, altretamine, ambroxycin, amethrone acetate, aminoglutethimide, amsacrine, anastrozole, amtricin, asparaginase, clindamycin, azacitidine, azatepa, azomycin, batimastat, benzotepa, bicalutamide, bisantrene hydrochloride, bisnefaddyl (dimesylate), bizelesin, bleomycin sulfate, brequina sodium, bripirimid, busulfan, actinomycin C, carpronine, carbitol, carbimide, carboplatin, carmustine, carvactin, carubicin hydrochloride, cambricin, sildenafil, gazelesin, cisplatin, cloritin, cyclophosphamide, cytarabine, dacarbazine hydrochloride, alcalazide, clotrimazole, aclonidine hydrochloride, aldicarin, aldicarb, Actinomycin D, daunorubicin hydrochloride, decitabine, dexomaplatin, dizagutanine, dizagutaline mesylate, diazaquinone, docetaxel, doxorubicin hydrochloride, droloxifene citrate, drotaandrosterone propionate, daptomycin, idatroxate, eflornithine hydrochloride, elsamicin, enloplatin, enpu's amine, epipipidine, epirubicin hydrochloride, erbulozole, isosbiprazole hydrochloride, estramustine phosphate sodium, etanidazole, etoposide phosphate, chlorphenesin, fazoline hydrochloride, fazarabine, fenretinide, fluorouracil deoxynucleoside, fludarabine phosphate, fluorouracil, flucitabine, fexolone, fostrexacin sodium, gemcitabine, hydroxyurea, idarubicin hydrochloride, ifosfamide, and pivalose, Interleukin II (including recombinant interleukin II or rIL2), interferon alpha-2 a, interferon alpha-2 b, interferon alpha-n 1, interferon alpha-n 3, interferon beta-I a, interferon gamma-I b, iproplatin, irinotecan hydrochloride, lanreotide acetate, letrozole, leuprolide acetate, liazole hydrochloride, lometrexol sodium, lomustine, losoxantrone hydrochloride, maxol, maytansine, mechlorethamine hydrochloride, megestrol acetate, melphalan, melnolreil, mercaptopurine, methotrexate sodium, chlorpheniramine, meltupiprazole, mitodomide, mitocaine, mitogen, mitoxantrone hydrochloride, mitoxantrone, mycophenolate mofetil, norrhabdomycin, oxsulam, sumatriptan, mitoxantrone hydrochloride, mycophenolate mofetil, norgestimatinib, oxsultam, oximazone, and its salts, Paclitaxel, pemetrexed, pellicitein, nemustine, pelomomycin sulfate, perfosfamide, pipobroman, piposulfan, piroxolone hydrochloride, plicamycin, promethacin, promemetan, porfimer sodium, pofilomycin, prednimustine, procarbazine hydrochloride, puromycin hydrochloride, pyrazolofuranin, libadenosin, roguinimine, safrog, saffimgo hydrochloride, semustine, octreozine, sodium phosphonoaspartamate, sparamycin, spirogermanium hydrochloride, spiromustine, spiroplatinum, streptonigrin, streptozocin, sulfachlorphenamine, talithromycin, tegolan sodium, tegafur, tilloanthraquinone hydrochloride, temoporfin, teniposide, temoxicolone, testolactone, thioprimidine, thioguanine, tipepitosporipine, trexolone acetate, thalidomide phosphate, trimetrexate, tricriptan, tricirisone, trexate, triptorelin, trexate, troloxacin, trexate, tre, Tobramole hydrochloride, uramustine, uretipide, vapreotide, verteporfin, vinblastine sulfate, vincristine sulfate, vindesine sulfate, vinepidine sulfate, vinglycinate sulfate, vinblastine epoxy sulfate, vinorelbine tartrate, vinisovinblastine sulfate, vinzolidine sulfate, vorozole, zeniplatin, sethoxydim, and zorubicin hydrochloride.

Examples of other anti-cancer agents include, but are not limited to, 20-epi-1, 25 dihydroxyvitamin D3, 5-ethynyluracil, abiraterone, aclarubicin, acylfulvene, adecanenol, adolesin, aldesleukin, ALL-TK antagonist, altretamine, ammustine, amidodox, amifostine, aminolevulinic acid, amrubicin, amsacrine, anagrelide, anastrozole, andrographolide, angiogenesis inhibitor, antagonist-D, antagonist-G, enriches, anti-dorsal morphogenetic protein-1 (dorsaldizing morphogenic protein-1), anti-androgenic and prostate cancer drugs, anti-estrogenic drugs, anti-tumorinone, antisense oligonucleotides, glycine aphidicolin, apoptotic gene modulators, apoptotic modulators, purine-free (nuclear) acids, ara-CDP-DL-PTBA, ADBA, ADP-B-P-B-D-, Arginine deaminase, asulamine, atamestan, amoxastine, axinostatin 1, axinostatin 2, axinostatin 3, azasetron, azatoxin, diazotyrosine, baccatin III derivatives, balanol, batimastat, BCR/ABL antagonists, benzochlororins, benzostaurosporine, beta lactam derivatives, beta-alethine, beta-clarithromycin B (betabetacamycin B), betulinic acid, bFGF (basic fibroblast growth factor) inhibitors, bicalutamide, binitrogen, bicyclic ethylenespermidine (bisaziridinylspermine), bisnefadine, bistratene A, bizelesin, brefellate, bripirimidine, brazzein, buthionine sulfoxide (buthionine sulfoximine), xanthatriptan, carboximide, carboximidamide, carboximide-2-amide derivatives, carboximide, carboxim, Carzelin, Casein kinase Inhibitor (ICOS), castanospermine, cecropin B, cetrorelix, chlorelins, chloroquinoxalinylsulphane, cetaprost, cis porphyrin, cladribine, clomiphene analogs, clotrimazole, colismicin A, colismicin B, combretastatin A4, combretastatin analogs, conagenin, crambescidin 816, clinatol, cryptophycin 8 (a depsipeptide antineoplastic), Nostocin A derivatives, curculin A, cyclopentadecanone, cycloplatam, cyclopeptide, cytarabine ocfosfate, cytolytic factor, hexestrol phosphate, daclizumab, decitabine, cyclopeptide compounds dehydromembrane sphingosine B (dehydrodidemdemm B), deslorestrine, dexamethasone, dexamphetamine (dexrazine), dexrazoxane (dexrazoxane), dexrazoxane (D-methyl B, didox), dexrazoxane, Dihydro-5-azacytidine, 9-dihydrotaxol, dioxamycin, biphenylspiromustine, docetaxel, docosanol, dolasetron, doxifluridine, droloxifene, dronabinol, duocarmycin SA, ebselen, etokamostine, edelfosine, eculizine, elemene, ethirimol, epirubicin, epristeride, estramustine analogs, estrogen agonists, estrogen antagonists, etanidazole, phosphoside, exemestane, fadazole, fazarabine, fenretinide, filgrastimide, finasteride, flavopiridol, flutrostine, flusterware, fludarabine, fluororubicin hydrochloride (fluodenomycin hydrochloride), foscarnitin hydrochloride, foxacillin hydrochloride, foxaphycin, foxagliclazide, trexatretin, gadolzine, ganaxolide, guazatine, valtretin, gadolzine, valtretin, guazatine, valtretin, valtrexadone, valtretin, Glutathione inhibitors, hepsulfam, heregulin, hexamethylenediethylamide, hypericin, ibandronic acid, idarubicin, idoxifene, implomenone, imofovir, ilomastat, imidazoloacridones (imidazolacridones), imiquimod, peptide immune promoters (immunostimmulmutliptides), insulin-like growth hormone-1 receptor inhibitors, interferon agonists, interferons, interleukins, iodobenzylguanidine, ioxamycin, 4-Ipomol, ipropal, isosorafen, isobengazole, isoomohalichondrin B, itaconitron, jasplakinolide, kahalalide F, lamelin-N triacetate, lanreotide, leinakainamycin, leupeptin, estrogenic polysaccharides, lentinan, letrostastatin, leuprolide + L-alpha-leuprolide, L-alpha-beta-N triacetate, and L-alpha-leuprolide, L-alpha-beta-D-L triacetate, L-L, Lipophilic platinum compounds, lissoclinide 7, lobaplatin, earthworm phospholipids, lometrexol, lonidamine, losoxantrone, lovastatin, loxoribin, lurtotecan, lutetium photosensitizer, lysofylline, lysozyme, maytansine, mannostatin A, marimastat, maxolone, maspin, matrilysin inhibitors (matrilysin inhibitors), matrix metalloproteinase inhibitors (matrilysin inhibitors), melanopril, thiobarbital (merbarone), mettirelin, methicillin, metoclopramide, macrophage inhibitor (MIF inhibitor), mifepristone, miltefosine, mitosin, mismatching bigeminal RNA, mitoxantrone, mitomycin analogs, mitoxantrone, cytotoxin fibroblast growth factor (mitoxantrone), loxogradin, monoclonal antibody growth factor, lamivudine, leupeptin, leuprolide, and/or a, Human chorionic gonadotropin monoclonal antibodies, monophosphoryl lipid A + myobacterium cell wall sk, mopidamol, multi-drug resistant gene inhibitors, multiple tumor suppressor gene-1 based therapies (multiple tumor suppressor1-based therapeutics), nitrogen mustard anticancer agents, mycaproxide B, mycobacterial cell wall extracts, myriaptone, N-acetyldinaline, N-substituted benzamides, nafarelin, narbespray, naloxone + pentazocine, napavin, napreppin, nartostatin, nedaplatin, nemorubicin, neridronic acid, neutral endopeptidase, nilutamide, nisamycin, nitric oxide modulators, nitric oxide antioxidants (nitroxidazada), nitryl, O6-benzylguanine, oxolone, tritonine, oligonucleotides, oxolone, oncostatin, oxolone, angiotensin I-A-1-B, and pharmaceutically acceptable salts thereof, Oxaliplatin, oxanonomycin, paclitaxel analogs, paclitaxel derivatives, palauamine, palmitoylrhizoxin, pamidrophosphoric acid, panaxytriol, panomifene, parabaccin, pazetidine, pemetrexed, pedexrazoxane, pentostatin, pentazole, perfluorobromoalkane, phosphoramide, perillyl alcohol, phenazinomicin, phenyl acetate, phosphatase inhibitors, hemolytic streptococcal agents (immunopotentiators), pilocarpine hydrochloride, pirarubicin, pirtroxine, placetin A, placetin B, plasminogen activator inhibitors, platinum complexes, platinum compounds, platinum-triamine complexes, porphine sodium, podofycin, prednisone, propyldi-acridone, prostaglandin J2, protease inhibitors, protein A-based immunomodulators, protein kinase C inhibitors, microalgal protein kinase C inhibitors, Protein tyrosine phosphatase inhibitors, purine nucleoside phosphorylase inhibitors, purpurins, pyrazoloacridines, pyridoxylated hemoglobin polyethylene oxide conjugates, rafafatagonists, raltitrexed, ramosetron, ras farnesyl protein transferase inhibitors, ras-GAP inhibitors, demethylated reteplatin, rhenium (Re)186 glycolate, rhizomycin, ribozymes, RII retinoamide (RII retinamide), roguinimine, rohituine, romotein, roquinmerac, rubiginone B1, ruboxyl, safranol, saintopin, SarCNU (2-chloroethyl-3-sarcosinamide-1-nitrosourea), sarcophytol A, sargrastim, Sdi 1 mimetics, semustine, senescens derived inhibitors of cell origin 1 (cytostatic inhibitors), inhibitory agents of signal transduction of signal 1, oligonucleotides, and inhibitors of signal transduction of ras farnesyl, Single chain antigen binding protein, cizopyran, sobuzosin, sodium boro-caborate (sodium boro-caborate), sodium phenylacetate, solverol, growth hormone binding protein, solimine, phosphonowinteric acid, spicamycin D, spiromustine, splenopin, spongistatin 1, squalamine, stem cell inhibitors, stem cell differentiation inhibitors (stem-cell differentiation inhibitors), stimamides, matrix degrading enzyme inhibitors (stromelysinhibitors), sulfinosine, potent vasoactive intestinal peptide antagonists, suradista, suramin, swamsoline, synthetic glycosaminoglycans, tamoxifen, taurocysteine, tazarotene, tegolazine, tegafur, pyrylium salt (tellurophyridium), angiogenin (telopodase) inhibitors, teniposide, temozoloside, thymopentin receptor, platelet receptor, thromboxane, and the like, Thymotreonam, thyroid stimulating hormone, tolteromycin ethyl ester (tin ethyl thiopururin), tirapazamine, cyclopentadienium dichloride, topstein, toremifene, totipotent stem cell factor, translation inhibitor, tretinoin, triacetyluridine, triciribine, trimetrexate, triptorelin, tropisetron, tolongeurea, tyrosine kinase inhibitor, tyrphostins, UBC inhibitor, UBC, ubenimex, urogenital sinus derived growth inhibitor, urokinase receptor antagonist, vapreotide, variolin B, carrier system, erythrocytic gene therapy, vilareol, veratramine, verteporfin, vinorelbine, vinxaline, vitaxin, vorazole, zanoteron, zeniplatin, benzalkonium, and lasertistin.

Examples of useful therapeutic agents for treating or preventing UI include, but are not limited to, Pribosine, imipramine, hyoscyamine, oxybutynin, and dicyclovirine.

Examples of useful therapeutic agents for treating or preventing ulcers include, but are not limited to, antacids such as aluminum hydroxide, magnesium hydroxide, sodium bicarbonate, and calcium bicarbonate; sucralfate; bismuth compounds such as bismuth subsalicylate and bismuth subcitrate; h₂Antagonists, such as cimetidine, ranitidine, famotidine and nizatidine; h⁺，K⁺-ATPase inhibitors such as omeprazole, iansoprazole and lansoprazole; (ii) a carbenoxolone; misprotol; and antibiotics such as tetracycline, metronidazole, tinidazole (timidazole), clarithromycin, and amoxicillin.

Examples of useful therapeutic agents for treating or preventing inflammatory bowel disease include, but are not limited to, anticholinergics; diphenoxylate; loperamide; deodorizing tincture of opium; codeine; broad spectrum antibiotics, such as metronidazole; sulfasalazine; oxalazine; mesalazine; prednisone; azathioprine; mercaptopurine, and methotrexate.

Examples of useful therapeutic agents for treating or preventing irritable bowel syndrome include, but are not limited to, pullulan; muscarinic receptor antagonists such as pirenzepine hydrochloride, methotrimesom, ipratropium, tiotropium, scopolamine, methscopolamine, homatropine, methemotropium, and pyrimethamine; and antidiarrheals such as diphenoxylate and loperamide.

Examples of useful therapeutic agents for treating or preventing an addictive disorder include, but are not limited to, methadone, desipramine, amantadine, fluoxetine, buprenorphine, opiate agonists, 3-phenoxypyridine, levomethadol hydrochloride, and 5-hydroxytryptamine antagonists.

Examples of useful therapeutic agents for treating or preventing parkinson's disease include, but are not limited to, carbidopa/levodopa, pergolide, bromocriptine, ropinirole, pramipexole, entacapone, tolcapone, selegiline, amantadine, and diphenhydramine hydrochloride.

Examples of useful therapeutic agents for treating or preventing anxiety include, but are not limited to, benzodiazepinesClasses, e.g. alprazolam, brotizolam, chlorazinesLoratadine, clonazepam, chlordiazepoxideDiazepam, estazolam, flumazenil, flurazepam, halazepam, lorazepam, midazolam, nitrazepam, desmetazepam, oxazepam, pramipepam, quazepam, temazepam, and triazolam; non-benzo (o) diazepinesSteroids such as buspirone, gepirone, ipsaprinone, tepirone, zolpicone, zolpidem, and zaleplon; sedatives, such as barbiturates, e.g., amobarbital, alprenol, sec-butyl barbital, tolbarbital, methohexital, pentobarbital, phenobarbital, secobarbital, and thiopental sodium; and propylene glycol carbamate(s), such as meprobamate and tiabamate.

Examples of useful therapeutic agents for treating or preventing epilepsy include, but are not limited to, carbamazepine, ethosuximide, gabapentin, lamotrigine (lamotrigine), phenobarbital, phenytoin, primidone, valproic acid, trimethadione, bemzodiaepines, gabapentin, lamotrigine, gamma-vinylgamma aminobutyric acid (gamma-vinyl GABA), acetazolamide, and felbamate.

Examples of useful therapeutic agents for treating or preventing stroke include, but are not limited to, anticoagulant (blood) agents (e.g., heparin), agents that break up blood clots (e.g., streptokinase or tissue plasminogen activator), agents that reduce edema (e.g., mannitol or corticosteroids), and aspirin.

Examples of useful therapeutic agents for treating or preventing a seizure include, but are not limited to, carbamazepine, ethosuximide, gabapentin, lamotrigine, phenobarbital, phenytoin, primidone, valproic acid, trimethadione, bemzodiaepines, gabapentin, lamotrigine, gamma-vinylgammabutyric acid, acetazolamide, and felbamate.

Examples of useful therapeutic agents for treating or preventing pruritis include, but are not limited to, naltrexone, nalmefene, danazol; tricyclic antidepressants such as amitriptyline, imipramine and doxepin; antidepressants as listed below, menthol; camphor; phenol; pramoxine; capsaicin; tar oil; a steroid; and an antihistamine.

Examples of useful therapeutic agents for treating or preventing psychosis include, but are not limited to, phenothiazines such as chlorpromazine hydrochloride, mesoridazine besylate, and thoradazine hydrochloride; thioxanthenes, such as chlorprothixene and thiothixene hydrochloride; clozapine; risperidone; olanzapine; quetiapine; quetiapine fumarate; haloperidol; haloperidol decanoate; loxapine succinate; molindone hydrochloride; pimozide and ziprasidone.

Examples of useful therapeutic agents for treating or preventing Huntington's disease include, but are not limited to, haloperidol and pimozide.

Examples of useful therapeutic agents for treating or preventing ALS include, but are not limited to, baclofen, neurotrophic factors, riluzole, tizanidine, benzodiazepinesAnd (d) such as clonazepan (clonazepan) and dantrolene.

Examples of useful therapeutic agents for treating or preventing cognitive disorders include, but are not limited to, drugs for treating or preventing dementia, such as tacrine; donepezil; ibuprofen; antipsychotics, such as thioridazine and haloperidol; and antidepressants as described below.

Examples of useful therapeutic agents for treating or preventing migraine include, but are not limited to, sumatriptan, mexican, ergotamine, caffeine and beta-blockers, such as propranolol, verapamil and divalproex sodium.

Examples of useful therapeutic agents for treating or preventing emesis include, but are not limited to, 5-HT₃Receptor antagonists such as ondansetron, dolasetron, granisetron and tropisetron; dopamine receptor antagonists such as prochlorperazine, thiethylperazine, chlorpromazine, metoclopramide, and domperidone; glucocorticoids, such as dexamethasone; and benzodiazepinesAnd (d) such as lorazepam and alprazolam.

Examples of useful therapeutic agents for treating or preventing dyskinesias include, but are not limited to, reserpine and tetrabenazine.

Examples of useful therapeutic agents for treating or preventing depression (symptoms) include, but are not limited to, tricyclic antidepressants such as amitypine, amoxapine, bupropion, clomipramine, desipramine, doxepin, imipramine, meprotiline (maprotiline), naftoprazone, nortriptyline, protriptyline, trazodone, trimipramine, and venlafaxine (venlafaxine); selective 5-hydroxytryptamine reuptake inhibitors such as fluoxetine, fluvoxamine, paroxetine, and sertraline; monoamine oxidase inhibitors such as isocarboxazid, pargyline, phenelzine and tranylcypromine; and psychostimulants such as dextroamphetamine and methylphenidate.

The benzoxazole piperazine compounds may be used in addition to, or in one embodiment synergistically with, other therapeutic agents. In one embodiment, a benzoxazole piperazine compound and another therapeutic agent are administered simultaneously. In one embodiment, a composition comprising an effective amount of one benzoxazole piperazine compound and an effective amount of another therapeutic agent may be administered. Alternatively, a composition comprising an effective amount of one benzoxazole piperazine compound and a different composition comprising an effective amount of another therapeutic agent may be administered simultaneously. In another embodiment, an effective amount of a benzoxazole piperazine compound is administered before or after an effective amount of another therapeutic agent. In this embodiment, the benzoxazole piperazine compound is administered while the other therapeutic agent exerts its therapeutic effect, or the other therapeutic agent is administered while the benzoxazole piperazine compound exerts its therapeutic or prophylactic effect, to treat or prevent a disease in an animal.

The compositions of the present invention are prepared by a process comprising admixing the benzoxazole piperazine compound with a pharmaceutically acceptable carrier or excipient. Mixing is accomplished using well known methods of mixing the compound (or salt) and the pharmaceutically acceptable carrier. In one embodiment, an effective amount of the benzoxazole piperazine compound is present in the composition.

4.3.2 medicament box

The invention includes kits that simplify the administration of benzoxazole piperazine compounds to animals.

A typical kit of the invention comprises a unit dosage form of a benzoxazole piperazine compound. In one embodiment, the unit dosage form is a container, which may be sterile, containing an effective amount of the benzoxazole piperazine compound and a pharmaceutically acceptable carrier. The kit may further include a label or printed instructions for use that instructs the use of the benzoxazole piperazine compound to treat the following disease or condition: pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, Parkinson's syndrome, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression. The kit may also include a unit dosage form of the other therapeutic agent, e.g., a container containing an effective amount of the other therapeutic agent. In one embodiment, the kit comprises a container containing an effective amount of a benzoxazole piperazine compound and an effective amount of another therapeutic agent. Examples of other therapeutic agents include, but are not limited to, those listed above.

The kit of the present invention may also include a device for administering the unit dosage form. Examples of such devices include, but are not limited to, syringes, drip bags, patches, inhalers, and enema bags.

The following examples are set forth to aid in the understanding of the present invention and, of course, should not be construed to specifically limit the invention described and claimed herein. Such variations of the invention, including all equivalent substitutions now known or later developed, are within the knowledge of one skilled in the art, and modifications in formulation or minor changes in experimental design are considered to be within the scope of the invention as constructed herein.

5. Examples of the embodiments

5.1. Example 1: synthesis of Benzoxazole piperazine Compounds of formula (Ia) AAM, AAS, AAQ, AAP, AYF, AYD, AZW, AZZ, AYH, AYE, AYI, AYK, AYG, AYC, AZA, AZD, AYN, and AYM

Benzoxazole piperazine compounds of formula (Ia)

A DMSO solution of 2-chloro-3-X-pyridine 1 (about 0.5M to about 1M) and 1 equivalent of 2-Q-piperazine 2 was heated to about 140 ℃ for about 2-4h with stirring. The resulting reaction mixture was then cooled to room temperature and DMSO was removed under reduced pressure to give compound 3.

In a separatory funnel, 0.75 equivalents of a Dichloromethane (DCM) solution of chloroformate 4 (0.04M) was cooled to 0 deg.C, and then 0.75 equivalents of 5-Z-6-Y-benzothiazol-2-ylamine 5 was slowly added to the cooled solution of chloroformate 4. The resulting reaction mixture was stirred at 0 ℃ for 5 minutes, and then 5 equivalents of triethylamine were added to the reaction mixture. The reaction mixture was then warmed to room temperature and concentrated under reduced pressure at 40 ℃ to give compound 6.

Compound 6 was dissolved in DCM (0.1M), 1 equivalent of a 1M solution of 3 in DCM was added to the solution of compound 6 at rt, and the resulting reaction mixture was stirred for 10 min. The reaction mixture was then concentrated under reduced pressure at 40 ℃ to give the benzoxazolyl piperazine compound of formula (Ia). The benzoxazole piperazine compound of formula (Ia) was purified by silica gel column eluting with 5: 95 ethyl acetate/hexane.

Table XXIII lists benzoxazole piperazine compounds prepared according to the method of example 1.

TABLE XXIII

Benzoxazole piperazine compound	X	Q	Y	Z
					AAM	-Cl	-H	-Cl	-H
AAS	-Cl	-H	-OCHCH	-H
					AAQ	-Cl	-H	-CF	-H
AAP	-Cl	-H	-CH	-H
					AYF	-Cl	(R)-CH	-Br	-H
AYD	-Cl	(R)-CH	-H	-H
					AZW	-CF	(R)-CH	-Cl	-H
AZZ	-CF	(R)-CH	-CH	-H
					AYH	-Cl	(R)-CH	-CH	-H
AYE	-Cl	(R)-CH	-Cl	-H
					AYI	-Cl	(R)-CH	-CF	-H
AYK	-Cl	(R)-CH	-OCHCH	-H
					AYG	-Cl	(R)-CH	-F	-H
AYC	-Cl	(R)-CH	-CH	-CH
					AZA	-CH	(R)-CH	-Cl	-H
AZD	-CH	(R)-CH	-CH	-H
					AYN	-Cl	(R)-CH	-CH(CH)	-H
AYM	-Cl	(R)-CH	-C(CH)	-H

(R)-CH₃The carbon atom to which the silyl group is attached is in the (R) configuration.

Identification of Compound AAM Using H¹NMR was used for confirmation.

A compound AAM:

¹H NMR(400MHz，CDCl₃)，δ8.24-8.19(m，1H)，7.77-7.76(m，1H)，7.67-7.64(m，1H)，7.57-7.54(m，1H)，7.38-7.36(m，1H)，6.95-6.90(m，1H)，3.77-3.75(m，4H)，3.45-3.42(m，4H).

identification of Compound AAS Using H¹NMR was used for confirmation.

A compound AAS:

¹H NMR(400MHz，CDCl₃)，δ10.17(s，1H)，8.19-8.15(m，1H)，7.61-7.58(m，1H)，7.51-7.46(m，.1H)，7.28-7.22(m，1H)，6.98-6.95(m，1H)，6.89-6.86(m，1H)，4.11-4.04(m，2H)，3.77-3.71(m，4H)，3.37-3.34(m，4H)，1.43(t，3H).

Identification of Compound AAQ Using H¹NMR was used for confirmation.

A compound AAQ:

¹H NMR(400MHz，CDCl₃)：δ8.22-8.19(m，1H)，8.09-8.05(m，1H)，7.76-7.71(m，1H)，7.66-7.64(m，2H)，6.94-6.91(m，1H)，3.80-3.75(m，4H)，3.47-3.45(m，4H).

identification of Compound AAP Using H¹NMR was used for confirmation.

A compound AAP:

¹H NMR(CDCL₃)，δ8.22-8.20(m，1H)，7.65-7.63(m，1H)，7.57-7.55(m，1H)，7.52-7.48(m，1H)，7.22-7.18(m，1H)，6.92-6.87(m，1H)，3.78-3.76(m，4H)，3.45-3.42(m，4H)，2.46(s，3H).

identification of Compound AYF Using H¹NMR was used for confirmation.

Compound AYF:

¹H NMR(CDCl₃)，δ8.23-8.20(m，1H)，7.93-7.90(m，1H)，7.67-7.62(m，1H)，7.54-7.50(m，2H)，6.95-6.91(m，1H)，4.45(bs，1H)，4.11-4.05(m，1H)，3.86-3.76(m，2H)，3.57-3.46(m，1H)，3.12-3.06(m，1H)，3.02-2.94(m，1H)，1.50(d，3H，J＝6.8).

identification of Compound AYD Using H¹NMR and mass spectroscopy.

Compound AYD:

¹H NMR(CDCl₃)，δ8.83(br，1H)，8.24-8.20(m，1H)，7.81-7.74(m，1H)，7.68-759(m，2H)，7.48-7.38(m，1H)，7.33-7.24(m，2H+CHCl₃)，6.96-6.87(m，1H)，4.55-4.43(m，1H)，4.17-4.06(m，1H)，3.89-3.75(m，2H)，3.58-3.42(m，1H)，3.16-2.89(m，1H)，1.45(d，3H，J＝6.8Hz).

(M+1)m/z：388.0.

identification of Compound AZW Using H¹NMR was used for confirmation.

Compound AZW:

¹H NMR(CDCl₃)，δ8.49-8.45(m，1H)，7.94-7.90(m，1H)，7.57-7.54(m，1H)，7.52-7.46(m，1H)，7.22-7.18(m，1H)，7.11-7.06(m，1H)，4.46(bs，1H)，4.09-4.00(m，1H)，3.52-3.42(m，2H)，3.38-3.33(m，1H)，3.25-3.19(m，1H)，3.04-2.96(m，1H)，1.39(d，3H，J＝6.8).

identification of Compound AZZ Using H¹NMR was used for confirmation.

Compound AZZ:

¹H NMR(CDCl₃)，δ8.50-8.46(m，1H)，7.94-7.91(m，1H)，7.55(bs，1H)，7.51-7.47(m，1H)，7.21-7.17(m，1H)，7.11-7.06(m，1H)，4.45(bs，1H)，4.09-4.01(m，1H)，3.53-3.45(m，2H)，3.41-3.34(m，1H)，3.26-3.20(m，1H)，3.07-2.95(m，1H)，2.46(s，3H)，1.38(d，3H，J＝6.7).

identification of Compound AYH Using H¹NMR was used for confirmation.

Compound AYH:

¹H NMR(CDCl₃)，δ8.71(bs，1H)，8.24-8.20(m，1H)，7.67-762(m，1H)，7.58(bs，1H)，7.55-7.49(m，1H)，7.25-7.19(m，1H)，6.94-6.89(m，1H)，4.46(bs，1H)，4.14-4.06(m，1H)，3.86-3.74(M，2H)，3.56-3.43(m，1H)，3.13-3.05(m，1H)，3.03-2.95(m，1H)，2.47(s，3H)，1.64(s，3H)，1.47(d，3H，J＝7.0).

identification of Compound AYEFixed use H¹NMR was used for confirmation.

Compound AYE:

¹H NMR(CDCl₃)，δ8.37(bs，1H)，8.24-8.21(m，1H)，7.77-7.75(m，1H)，7.67-7.64(m，1H)，7.61-7.57(m，1H)，7.39-7.35(m，1H)，6.95-6.90(m，1H)，4.40(bs，1H)，4.15-4.01(m，1H)，3.90-3.77(m，1H)，3.58-3.47(m，1H)，3.14-3.07(m，1H)，3.05-2.96(m，1H)，1.51(d，3H，J＝6.8).

identification of Compound AYI Using H¹NMR was used for confirmation.

Compound AYI:

¹H NMR(CDCl₃)，δ9.31(bs，1H)，8.22-8.19(m，1H)，8.08(bs，1H)，7.76-7.70(m，1H)，7.68-7.61(m，2H，6.94-.6.89(m，1H)，4.46(bs，1H)，4.11-4.02(m，1H)，3.85-3.74(m，2H)，3.59-3.48(m，1H)，3.12-3.05(m，1H)，3.02-2.92(m，1H)，1.49(d，3H，J＝6.8).

identification of Compound AYK Using H¹NMR was used for confirmation.

Compound AYK:

¹H NMR(CDCl₃)，δ9.40(bs，1H)，8.22-8.18(m，1H)，7.64-7.60(m，1H)，7.57-7.51(m，1H)，7.30-7.25(m，1H+CHCl3)，7.03-6.97(m，1H)，6.93-6.88(m，1H)，4.45(bs，1H)，4.14-4.00(m，3H)，3.81-3.69(m，2H)，3.53-3.43(m，1H)，3.09-3.02(m，1H)，3.00-2.91(m，1H)，1.48-1.43(m，6H).

identification of Compound AYG Using H¹NMR was used for confirmation.

Compound AYG:

¹H NMR(CDCl₃)，δ8.41(bs，1H)，8.24-8.20(m，1H)，7.68-7.56(m，2H)，7.52-7.46(m，1H)，7.18-7.11(m，1H)，6.95-6.90(m，1H).4.41(bs，1H)，4.09-4.02(m，1H)，3.89-3.77(m，2H)，3.58-3.49(m，1H)，3.14-307(m，1H)，3.05-2.96(m，1H)，1.5(d，3H，J＝6.8).

identification of Compound AYC Using H¹NMR was used for confirmation.

The compound AYC:

¹H NMR(CDCl₃)，δ8.23-8.19(m，1H)，765-7.61(m，1H)，7.52(bs，1H)，7.40(bs，1H)，6.93-6.88(m，1H)，4.50(bs，1H)，4.17-4.06(m，1H)，3.84-3.73(m，2H)，3.56-3.44(m，1H)，3.11-3.03(m，1H)，3.01-2.92(m，1H)，2.36(s，6H)，1.48(d.，3H，J＝6.8).

identification of Compound AZA Using H¹NMR was used for confirmation.

Compound AZA:

¹H NMR(CDCl₃)，δ8.93(bs，1H)，8.17-8.14(m，1H)，8.00-7.96(m，1H)，7.77(bs，1H)，7.60-7.53(m，1H)，7.41-7.33(m，1H)，4.49(bs，1H)，4.16-4.06(m，1H)，4.00-3.94(m，2H)，3.57-3.46(m，1H)，3.19-3.11(m，1H)，3.07-2.98(m，1H)，1.70(s，3H)，1.47(d，3H，J＝6.8).

identification of Compound AZD Using H¹NMR was used for confirmation.

Compound AZD:

¹HNMR(CDCl₃)，δ8.68(bs，1H)，8.21-8.18(m，1H)，7.61-7.43(m，3H)，7.24-7.19(m，1H)，6.94-6.90(m，1H)，4.45(bs，1H)，4.13-4.04(m，1H)，3.54-3.41(m，2H)，3.37-3.32(m，1H)，3.12-3.04(m，1H)，3.64-2.90(m 1H)，2.46(s，3H)，2.35(s，3H)，1.48(d，3H，J＝6.8).

identification of Compound AYN Using H¹NMR was used for confirmation.

Compound AYN:

¹H NMR(CDCl₃)，δ8.20-8.18(m，1H)，7.64-7.59(m，1H)，7.58-7.50(m，1H)，7.29-7.25(m，1H+CHCl₃)，6.91-6.87(m，1H)，4.49(bs，1H)，4.14-4.05(m，1H)，3.79-3.68(m，2H)，3.07-2.89(m，3H)，1.44(d，3H，J＝6.8)，1.31(d，3H，＝7.0).

identification of Compound AYM Using H¹NMR was used for confirmation.

Compound AYM:

¹H NMR(CDCl₃)，δ8.24-8.20(m，1H)，7.76(bs，1H)，7.66-7.62(m，1H)，7.55-7.52(m，.1H)，7.49-7.43(m，1H)，6.94-6.89(m，1H)，4.46(bs，1H)，4.16-4.07(m，1H)，3.87-3.73(m，2H)，3.56-3.45(m，1H)，3.14-3.05(m，1H)，3.04-2.91(m，1H)，1.49(d，3H，J＝6.8)，1.40(s，9H).：

5.2. example 2: synthesis of Benzoxazole piperazine Compounds BDJ and BDG of formula (Ib)

The compounds BDJ and BDG were prepared by an analogous method to that employed in example 1, but replacing 2-chloro-3-X-pyridine 1 with 2, 3-dichloropyrazine. In the preparation of compound BDJ, 2-Q-piperazine 2 is (R) -2-methylpiperidine and 5-Z-6-Y-benzothiazol-2-ylamine 5 is 6-methylbenzothiazol-2-ylamine. In the preparation of compound BDG, 2-Q-piperazine 2 is (R) -2-methylpiperidine and 5-Z-6-Y-benzothiazol-2-ylamine 5 is 6-chlorobenzothiazol-2-ylamine.

Identification of Compound BDJ Using H¹NMR was used for confirmation.

Compound BDJ:

¹H NMR(CDCl₃)，δ8.16-8.13(m，1H)，7.96-7.93(m，1H)，7.56(bs，1H)，7.47(bs，1H)，7.22-7.18(m，1H)，4.56(bs，1H)，4.19-4.13(m，1H)，3.94-3.85(m，2H)，3.49-3.41(m，1H)，3.13-3.06(m，1H)，3.01-2.94(m，1H)，2.45(s，3H)，1.41(d，3H，J＝6.9).

identification of Compound BDG Using H¹NMR was used for confirmation.

Compound BDG:

¹H NMR(CDCl₃)，δ8.66(bs，1H)，8.17-8.15(m，1H)，8.00-7.97(m，1H)，7.76(bs，1H)，7.59-7.54(m，1H)，7.40-7.35(m，1H)，4.47(bs，1H)，4.16-4.07(m，1H)，4.02-3.92(m，2H)，3.57-3.48(m，1H)，3.20-3.13(m，1H)，3.09-2.98(m，1H)，1.48(d，3H，J＝6.8).

5.3. example 3: synthesis of Benzoxazole piperazine Compounds of formula (Ib) BIL, BII and BJE

Compounds BIL, BII and BJE were prepared by an analogous method to that used in example 1, but using 4, 5-dichlorothiadiazole instead of 2-chloro-3-X-pyridine 1 to prepare compounds BIL and BII, and 4-methyl-5-chlorothiadiazole to prepare compound BJE. In the preparation of compound BIL, 2-Q-piperazine 2 is (R) -2-methylpiperidine and 5-Z-6-Y-benzothiazol-2-ylamine 5 is 6-methylbenzothiazol-2-ylamine. In the preparation of compounds BII and BJE, 2-Q-piperazine 2 is (R) -2-methylpiperidine and 5-Z-6-Y-benzothiazol-2-ylamine 5 is 6-chlorobenzothiazol-2-ylamine.

Identification of Compound BIL Using H¹NMR was used for confirmation.

Compound BIL:

¹H NMR(CDCl₃)，δ7.54(bs，1H)，7.49-7.42(m，1H)，7.24-7.17(m，1H)，4.55(bs，1H)，4.24-4.15(m，1H)， 4.02-3.89(m，2H)，3.54-3.39(m，1H)，3.21-3.12(m，1H)，3.11-3.02(m，1H)，2.46(s，3H)，1.46(d，3H，J＝6.8).

identification of Compound BII Using H¹NMR was used for confirmation.

Compound BII:

¹H NMR(CDCl₃)，δ8.64(bs，1H)，7.75(bs，1H)，7.58-7.51(m，1H)，7.41-7.34(m，1H)，4.50(bs，1H)，4.18-4.06(m，1H)，4.01-3.92(m，2H)，3.56-3.44(m，1H)，3.21-3.13(m，1H)，3.12-3.04(m，1H)，1.48(d，3H，J＝6.8).

identification of Compound BJE Using H¹NMR was used for confirmation.

Compound BJE:

¹H NMR(CDCl₃)，δ8.59(bs，1H)，7.73(bs，1H)，7.53-7.47(m，1H)，7.41-7.34(m，1H)，4.55(bs，1H)，4.23-4.14(m，1H)，3.59-3.46(m，1H)，3.43-3.38(m，1H).3.37-3.28(m，1H)，3.11-3.02(m，1H)，3.00-2.90(m，1H)，2.65(s，3H)，1.61(d，3H，J＝6.8).

5.4. example 4: synthesis of Benzoazole piperazine Compounds of formulae (IIa) and (IIb) CBG, CAW, CRU, CSE, DIS, DJC, DIQ, CSE, EAA, DZU, CTA, CTW, CRW and CSB

Benzoxazoles of the formulae (IIa) and (IIb)

Piperazine compounds

A DMSO solution of 2-chloro-3-X-pyridine 1 (about 0.5M to about 1M) and 1 equivalent of 2-Q-piperazine 2 was heated to about 140 ℃ for about 2-4h with stirring. The resulting reaction mixture was then cooled to room temperature and DMSO was removed under reduced pressure to give compound 3.

A solution of compound 3 (about 0.25mmol to about 1mmol) and 1 equivalent of compound 7 in about 3mL of toluene or xylene is heated at a temperature of about 140 deg.C to 150 deg.C for about 3 days. The resulting reaction mixture was then concentrated under reduced pressure to give a residue which was purified by flash chromatography (silica gel, gradient of 2% methanol: DCM-6% methanol: DCM).

Compound 7, wherein R₁₀to-H, can be obtained from commercially available Compound 8 or as shown below

Compound 8 (about 30mmol) and Carbodiimide (CDI) (commercially available from Sigma-Aldrich, st.louis, MO (www.sigma-aldrich.com)) (about 2 equivalents) were dissolved in THF (about 50 to about 150mL) and the reaction mixture was heated at reflux temperature for about 4 hours. The reaction mixture was concentrated under reduced pressure to give a residue. About 50 to about 100mL of ethyl acetate or ethyl acetate/hexane (20: 80 to about 40: 60) was added to the residue, and the resulting insoluble material was collected by filtration and washed with ethyl acetate or ethyl acetate/hexane (20: 80 to about 40: 60) to give Compound 9. Then the ratio was determined according to the standard in j.med.chem.40: 586-593(1997) reacting Compound 9 with POCl₃Reaction to give compound 7.

As shown below, from wherein R₁₀Compound 7 being-H, to give wherein R₁₀is-CH₃The compound (2) of (1) to (7),

8, wherein R₁₀is-H, 8, wherein R₁₀is-CH₃

NaH (about 2 equivalents) is added to the compound of formula 8, wherein R is₁₀To a solution of-H in DMF, the resulting mixture was stirred and allowed to warm to room temperature over 1 hour. Methyl iodide (about 1.2 equivalents) was then added to the solution and the resulting reaction mixture was stirred for several minutes. Then adding water to the reaction mixture to bring R therein ₁₀is-CH₃Compound 8 of (2) is precipitated, filtered, collected and dried.

Table XXIV lists benzoxazole piperazine compounds prepared according to the method of example 4.

TABLE XXIV

Benzoxazole piperazine compound	R	Y	Z	X	Q
						CBG	-H	-tert-butyl	-H	-Cl	-H
CAW	-H	-CH	-CH	-Cl	-H
						CRU	-H	-CH	-CH	-Cl	(R)-CH
CRU	-H	-CH	-CH	-Cl	(S)-CH
						CSE	-H	-tert-butyl	-H	-Cl	(R)-CH
DIS	-CH	-CH	-CH	-Cl	-H
						DJC	-CH	-tert-butyl	-H	-Cl	-H
DIQ	-CH	-H	-tert-butyl	-Cl	-H
						CSE	-H	-tert-butyl	-H	-Cl	(S)-CH
EAA	-CH	-tert-butyl	-H	-Cl	(R)-CH
						DZO	-CH	-H	-tert-butyl	-Cl	(R)-CH
CTA	-H	-tert-butyl	-H	-CH	(R)-CH
						CTW	-H	-tert-butyl	-H	-CF	(R)-CH
CRW	-H	-Cl	-H	-Cl	(R)-CH
						CSB	-H	-OCH	-H	-Cl	(R)-CH

(R)-CH₃The carbon atom to which the silyl group is attached is in the (R) configuration. (S) -CH₃The carbon atom to which the silyl group is attached is in the (S) configuration.

Identification of Compound CBG Using H¹NMR and mass spectroscopy.

Compound CBG:

¹H NMR(CD₃OD)，δ8.21(dd，1H，J1＝1.6Hz，J2＝4.8Hz)；7.77(dd，1H，J1＝1.6Hz，J2＝7.6Hz)；7.34(d，1H，J＝2Hz)；7.21(d，1H，J1＝0.4Hz，.J2＝8.4Hz)；7.14(dd，1H，J1＝2Hz，J2＝8.4Hz)；7.01(dd，1H，J1＝4.8Hz，J2＝7.6Hz)；3.70(m，，4H)；3.49(m，4H)；1.37(s，9H).

MS：370.2(M+1).

identification of Compound CAW Using H¹NMR and mass spectroscopy.

Compound CAW:

¹H NMR(CD₃OD)，δ8.25(dd，1H，J1＝1.6Hz，J2＝4.8Hz)；7.82(dd，1H，J1＝1.6Hz，J2＝8Hz)；7.06(dd，1H，J1＝4.8Hz，J2＝7.6Hz)；3.82(m，4H)；3.58(m，4H)；2.38(s，6H).

MS：342.1(M+1).

the compound CRU, wherein Q is (R) -CH₃Identification of (A) by use of H¹NMR and mass spectroscopy.

The compound CRU, wherein Q is (R) -CH₃：

¹H NMR(CD₃OD)，δ8.25(dd，1H，J1＝1.6Hz，J2＝4.8Hz)；7.82(dd，1H，J1＝2H，J2＝8Hz)；7.07(dd，1H，J1＝4.4Hz，J2＝8Hz)；4.30(m 1H)；3.90(m，4H)；3.26(dd，1H，J1＝13Hz，J2＝1.6Hz)；3.17(m，1H)；2.38(s，6H)；1.59(d，3H，J＝6.8Hz).

MS：356.1(M+1).

The compound CRU, wherein Q is (S) -CH₃Identification of (A) by use of H¹NMR and mass spectroscopy.

The compound CRU, wherein Q is (S) -CH₃：

¹H NMR(CD₃OD)，δ8.25(dd，1H，J1＝1.2Hz，J2＝4.4Hz)；7.81(dd，1H，J1＝1.6Hz，J2＝7.6Hz)；7.07(dd，1H，J1＝4.8Hz，J2＝7.6Hz)；4.31(m，1H)；388(m，4H)；3.26(dd，1H，J1＝3.6Hz，J2＝13Hz)；3.16(m，1H)；2.38(s，6H)；1.59(d，3H，J＝6.4Hz).

MS：356.1(M+1).

The compound CSE, wherein Q is (R) -CH₃Identification of (A) by use of H¹NMR and mass spectroscopy.

The compound CSE, wherein Q is (R) -CH₃：

¹H NMR(CD₃OD)，δ8.22(dd，1H，J1＝1.6Hz，J2＝4.8Hz0；7.78(dd，1H，J1＝1.6Hz，J2＝7.6Hz0；7.33(dd，1H，J1＝0.8Hz，J2＝2Hz)；7.19(dd，1H，J1＝0.8Hz，J2＝8.4Hz0；7.12(dd，1H，J1＝1.6Hz，J2＝8.4Hz)；7.02(dd，1H，J1＝4.8Hz，J2＝8Hz)；4.37(m，1H)；3.84(m，3H)：3.58(m，1H)；3.20(dd，1H，J1＝4Hz，J2＝12Hz)；3.08(dt，1H，J1＝3.2H.z，J2＝12Hz)；1.45(d，3H，J＝6.4Hz)；1.37(s，9H).

MS：420(M+36).

Identification of Compound DIS Using H¹NMR and mass spectroscopy.

A compound DIS:

¹H NMR(CD₃OD)，δ8.23(dd，1H，J1＝1.6Hz，J2＝4.8Hz)；7.78(dd，1h，J1＝2Hz，J2＝8Hz)；727(bs，1H)；7.14(bs，1H)；7.02(dd，1H，J1＝4.8Hz，J2＝7.6Hz)；3.69(s，3H)；3.56(m，4H)；3.45(m，4H)；2.39(s，3H)；2.35(s，3H).

MS：356.1(M+1).

identification of Compound DJC use H¹NMR and mass spectroscopy.

Compound DJC:

¹H NMR(CD₃OD)，δ8.23(dd，1H，1H＝1.6Hz，J2＝4.8Hz)；7.78(dd，1H，J1＝2Hz，J2＝8Hz)；7.53(dd，1H，J1＝0.8Hz，J2＝2Hz)；7.31(dd，1H，J1＝1.6Hz，J2＝8.4Hz)；7.26(dd，1H，J1＝0.4Hz，J2＝8.4Hz)；7.02(dd，1H，J1＝4.8Hz，J2＝8Hz)；3.70(s，3H)；3.57(m，4H)；3.47(m，4H)；1.39(s，9H).

MS：384.1(M+1).

Identification of Compound DIQ Using H¹NMR and mass spectroscopy.

Compound DIQ:

¹H NMR(CD₃OD)，δ8.23)(dd，1H，J1＝1.6Hz，J2＝4.8Hz)；7.78(dd，1H，J1＝2Hz，J2＝8Hz)；7.41(dd，1H，J1＝0.4Hz，J2＝8.4Hz)；7.36(d，1H，J＝1.2Hz)；7.29(dd，1H，J1＝1.6Hz，J2＝8.4Hz)；7.02(dd，1H，J1＝4.8Hz，J2＝7.6Hz)；3.70(s，3H)；3.57(m，4H)；3.47(m，4H)；1.41(s，9H).

MS：384.1(M+1).

compound CSE, wherein Q is (S) -CH₃Identification of (A) by use of H¹MR and mass spectroscopy.

Compound CSE, wherein Q is (S) -CH₃：

¹H NMR(CD₃OD)，δ8.22(dd，1H，J1＝1.6Hz，J2＝4.8Hz)；7.78(dd，1H，J1＝1.6Hz，J2＝7.6Hz)；7.34(d，1H，J＝1.6Hz)；7.20(d，1H，J＝8.4Hz)；7.13(dd，1H，J1＝2Hz，J2＝8.4Hz)；7.02(dd，1H，J1＝4.8Hz，J2＝8Hz)；4.36(m，1H)；3.85(m，3H)；3.60(dt，1H，J1＝2.8Hz，J2＝12Hz)；3.20(dd，1H，J1＝4Hz，J2＝12Hz)；3.08(dt，1H，J1＝3.2Hz，J2＝13Hz)；1.45(d，3H，J＝6.4Hz)；1.37(s，9H).

MS：420(M+36).

Compound EAA, wherein Q is (R) -CH₃Identification of (A) by use of H¹NMR and mass spectroscopy.

Compound EAA, whereinQ is (R) -CH₃：

¹H NMR (DMSO d₆)，δ8.23(dd，1H，J1＝1.6Hz，J2＝2.8Hz)；7.63(dd，1H，J1＝1.6Hz，J2＝7.6Hz)；7.61(d，1H，J1＝8.4Hz)；7.32(dd，1H，J＝2Hz，J2＝8Hz)；7.26(dd，1H，J1＝1.6Hz，J2＝8Hz)；6.90(dd，1H，J1＝4.8Hz，J2＝8Hz)；3.80(m，1H)；3.70(s，3H)；3.69(dd，1H，J1＝2.8Hz，J2＝12Hz)；3.63(m，1H)；3.45(m，2H)；3.35(m，1H)；3.24(dd，1H，J1＝7.6Hz，J2＝12Hz)；1.43(s，9H)；1.20(d，3H，J＝6.4Hz).

MS：398.1(M+1).

The compound DZO, wherein Q is (R) -CH₃Identification of (A) by use of H¹NMR and mass spectroscopy.

The compound DZO, wherein Q is (R) -CH₃：

¹H NMR(DMSO d₆)，δ8.23(dd，1H，J1＝2Hz，J2＝4.8Hz)；7.75(d)；7.63(dd，1H，J1＝2Hz，J2＝7.6Hz)；7.32(dd，1H，J1＝2Hz，J2＝8.4Hz)；7.20(d，1H，J＝8.4Hz)；6.89(dd，1H，J1＝4.8Hz，J2＝7.6Hz)；3.82(m，1H)；3.68(s，3H)；3.68(m，1H)；3.61(m，1H)；3.48(m，2H)；3.37(m，1H)；3.28(dd，1H，J1＝δHz，J2＝12Hz)；1.41(s，9H)；1.22(d，3H，J＝6.4Hz).

MS：398.3(M+1).

Compound CTA, wherein Q is (R) -CH₃Identification of (A) by use of H¹NMR and mass spectroscopy.

Compound CTA, wherein Q is (R) -CH₃：

¹H NMR(CDCl₃)，δ8.17(d，1H，J＝4.8Hz)；7.44(d，1H，J＝7.6Hz)；7.42(s，1H)；7.27(d，1H，J＝8.4Hz)；7.13(d，1H，J＝8.4Hz)；6.91(dd，1H，J1＝4.8Hz，J2＝7.2Hz)；4.42(m，1H)；3.97(d，1H，J＝12Hz)；3.62(dt，1H，J1＝3.2Hz，J2＝12Hz)；3.47(d，1H，J＝12Hz)；3.33(d，1H，J＝13Hz)；3.18(dd，1H，J1＝3.2Hz，J2＝12Hz)；3.06(dt，1H，J1＝2.8Hz，J2＝12Hz)；2.32(s，3H)；1.45(d，3H，J＝6.8Hz)；1.33(s，9H).

MS：364.2(M+1).

The compound CTW, wherein Q is (R) -CH₃Identification of (A) by use of H¹NMR and mass spectroscopy.

The compound CTW, wherein Q is (R) -CH₃：

¹H NMR(CDCl₃)，δ8.49(d，1H，J＝4.8Hz)；7.93(dd，1H，J1＝1.6Hz，J2＝8.0Hz)；7.42(s，1H)；7.26(d，1H，J＝8.4Hz)；7.14(dd，1H，J1＝1.6Hz，J2＝8.4Hz)；7.08(dd，1H，J1＝4.8Hz，J2＝8.0Hz)；4.37(m，1H)；3.89(d，1H，J＝12Hz)；3.64(dt，1H，J1＝3.2H，J2＝12Hz)；3.56(d，1H，J＝13Hz；3.45(d，1H，J＝13Hz)；3.37(dd，1H，J1＝3.6Hz，J2＝12Hz)；3.17(dt，1H，J1＝3.2Hz，J2＝12Hz)；1.39(d，3H，J＝6.8Hz)；1.35(s，9H).

MS：418.2(M+1).

The compound CRW, wherein Q is (R) -CH₃Identification of (A) by use of H¹NMR and mass spectroscopy.

The compound CRW, wherein Q is (R) -CH₃：

¹H NMR(CD₃OD)，δ8.21(dd，1H，J1＝1.6Hz，J2＝4.8Hz)；7.78(dd，1H，J1＝1.6Hz，J2＝7.6Hz)；7.24(s，1H)；7.20(d，1H，J＝8Hz)；7.02(dd，1H，J1＝4.8Hz，J2＝8Hz)；7.01(d，1H，J＝8Hz)；4.36(m，1H)；3.86(m，3H)；3.62(dt，1H，J1＝3.2Hz，J2＝12Hz)；3.18(dd，1H，J1＝2.8Hz，J2＝13Hz)；3.07(dt，1H，J1＝3.2Hz，J2＝13Hz)；1.46(d，3H，J＝6.8Hz).

MS：362.1(M+1).

Compound CSB, wherein QIs (R) -CH₃Identification of (A) by use of H¹NMR and mass spectroscopy.

The compound CSB, wherein Q is (R) -CH₃：

¹H NMR(CD₃OD)，δ8.24(dd，1H，J1＝1.8Hz，J2＝4.8Hz)；7.80(dd，1H，J1＝1.8Hz，J2＝7.9Hz)；4.31(m，1H)；3.91(m，2H)；3.80(dt，1H，J1＝3.5Hz，J2＝12Hz)；3.25(dd，1H，J1＝3.2Hz，J2＝12Hz)；3.15(dt，1H，J1＝4.0Hz，J2＝12Hz)；1.56(d，3H，J＝6.6Hz).

MS：358.1(M+1).

5.5. Example 5: synthesis of Benzoxazole piperazine Compound DBM of formula (IIb)

Compound DBM, wherein R₃Is (R) -CH₃Prepared by an analogous method to that used in example 4, but replacing 2-chloro-3-X-pyridine 1 with 4, 5-dichlorothiadiazole and 2-Q-piperazine 2 is 2- (R) -methylpiperazine and 5-Z-6-Y-2-chloro-1-H-benzimidazole 7 is 6-tert-butyl-2-chloro-1-H-benzimidazole.

Compound DBM, wherein Q is (R) -CH₃Identification of (A) by use of H¹NMR and mass spectroscopy.

Compound DBM, wherein Q is (R) -CH₃：

¹H NMR(CD₃OD)，δ7.34(s，1H)；7.20(d，1H，J＝8.4Hz)；7.13(dd，1H，J1＝1.6Hz，J2＝8.4Hz)；4.38(m，1H)；4.05(bd，2H，J＝12Hz)；3.90(bd，1H，J＝13Hz)；3.58(dt，1H，J1＝3.6Hz，J2＝12Hz)；3.27(dd，1H，J1＝3.6Hz，J2＝12Hz)；3.20(dt，1H，J1＝3.6Hz，J2＝12Hz)；1.43(d，3H，J＝6.4Hz)；1.37(s，9H).

MS：391.1(M+1).

5.6. Example 6: synthesis of Benzoxazole piperazine Compounds of formula 10

Benzoxazole piperazine compounds of formula 10

Prepared by an analogous method to that employed in example 4, using compound 7, where Y is-CH₃And Z is-CH (CH)₃)₂And 2- (R) -methylpiperazine is used instead of 2-Q-piperazine 2.

Compound 10, wherein Q is (R) -CH₃Identification of (A) by use of H¹NMR and mass spectroscopy.

Compound 10, wherein Q is (R) -CH₃

¹H NMR(CD₃OD)，δ8.22(dd，1H，J1＝1.8Hz，J2＝4.9Hz)；7.78(dd，1H，J1＝1.6Hz，J2＝8.0z)；7.20(s，1H)；7.04(dd，1H，J1＝4.9Hz，J2＝7.7Hz)；4.35(m，1H)；3.85(m，3H)；3.62(dt，1H，J1＝3.3Hz，J2＝12Hz)；3.21(m，2H)；3.06(dt，1H，J1＝4.0Hz，J2＝13Hz)；2.40(s，3H)；1.47(d，3H，J＝6.8Hz)；1.27(d，6H，J＝6.8Hz).

MS：384.1(M+1).

5.7. Example 7: benzoxazole piperazine compounds FUY and EXG of formula (IIIa)

Benzoxazole piperazines of formula (IIIa)

Compound 3 (about 1mmol) (prepared as described above in example 5.1) and 1 equivalent of compound 11 were dissolved in toluene or p-xylene (about 0.5 to about 1mL) and the resulting reaction mixture was heated in a sealed tube at a temperature of about 150 ℃ for about 24 h. The reaction mixture was then concentrated under reduced pressure to give a residue. The residue obtained is purified by flash chromatography (silica gel, 5% methanol: DCM) to give the benzoxazole piperazine compound of formula (IIIa).

Compound 11 was obtained as described below

Compound 12 (about 15 to about 20mmol) and 1 equivalent of compound 13 are dissolved in ethanol (about 30 to about 40mL) and the resulting reaction mixture is heated at reflux temperature for about 5 h. The reaction mixture was then concentrated under reduced pressure to give a residue which was diluted with water (about 30mL) and acidified with acetic acid to a pH of about 6. The aqueous layer mixture was extracted with ethyl acetate, the resulting ethyl acetate was dried (sodium sulfate), and the solvent was removed under reduced pressure to give compound 7, which was used without further purification.

Table XXV lists benzoxazole piperazine compounds prepared according to the method of example 7.

TABLE XXV

Benzoxazole piperazine compound	Y	Z	X	Q
					FUY	-H	Tert-butyl radical	-Cl	(R)-CH
EXG	-H	Tert-butyl radical	-Cl	-H

(R)-CH₃The carbon atom to which the silyl group is attached is in the (R) configuration.

Identification of Compound FUY Using H¹NMR and mass spectroscopy.

Compound FUY:

¹H NMR(CDCl₃)，δ8.23(dd，1H，J1＝1.6Hz，J2＝4.8Hz)；7.65(dd，1H，J1＝2Hz，J2＝7.6Hz)；7.47(d，1H，J＝2Hz)；7.20(d，1H，J＝8.4Hz)；7.10(dd，1H，J1＝2Hz，J2＝8.4Hz)；6.91(dd，1H，J1＝4.8Hz，J2＝8Hz)；4.60(m，1H)；4.60(d，1H，J＝13Hz)；3.84(m，2H)；3.67(dt，1H，J1＝3.6Hz，J2＝13Hz)；3.17(dd，1H，J1＝4Hz，J2＝12Hz)；3.08(dt(1H，J1＝3.2Hz，J2＝12Hz；1.52(d，3H，J＝6.8Hz)；1.37(s，9H).

MS：385.2(M+1).

compound EXG, wherein Q is (R) -CH₃Identification of (A) by use of H¹NMR and mass spectroscopy.

Compound EXG:

¹H NMR(CDCl₃)，δ8.23(dd，1H，J1＝1.6Hz，J2＝4.8Hz)；7.65(dd，1H，J1＝2Hz，J2＝7.6Hz)；7.46(d，1H，J＝1.6Hz)；7.20(dd，1H，J1＝0.4Hz，J2＝8.4Hz)；7.10(dd，1H，J1＝2Hz，J2＝8.4Hz)；6.91(dd，1H，J1＝5.2Hz，J2＝7.6Hz)；3.88(m，4H)；3.50(m，4H)；1.37(s，9H).

MS：371.1(M+1).

5.8. example 8: synthesis of benzoxazole piperazine compound FIU of formula (IIIa)

Compound FIU was prepared by an analogous method to that employed in example 1, but replacing 5-Z-6-Y-benzothiazol-2-ylamine with 5-chloro-benzoxazol-2-ylamine.

Identification of Compound FIU Using H¹NMR and mass spectroscopy.

Compound FIU:

¹H NMR(CDCl₃，δ11.45(bs，1H)，8.23-8.18(m，1H)，7.66-7.61(m，1H)，7.25-7.21(m，1H)， 7.18-7.12(m，1H)，6.92-6.86(m，1H)，5.06-4.71(，1H)，4.67-4.32(m，1H)，3.87-3.72(m，2H)，3.56-3.29(m，1H)，3.07-2.86(m，2H)，1.45(d，3H，J＝6.8).

5.9. example 9: synthesis of Benzoxazole piperazine Compounds of formula 14

2-amino-6-methyl-benzothiazole 15(2.0mmol, 328mg) (commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma-Aldrich. com)) and 1, 1' -thiocarbonyldiimidazole (2.0mmol, 356mg) (commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma-Aldrich. com)) were suspended in DMSO (3 mL). 4-dimethyl-aminopyridine (30mg) (commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma-Aldrich. com)) was then added to the suspension, and the resulting reaction mixture was heated to 100 ℃ and stirred at 100 ℃ for about 6 hours. The reaction mixture was then cooled to room temperature and (R) -4- (3-chloro-2-pyridyl) -2-methylpiperazine (2.0mmol, 422mg) (commercially available from Sigma-Aldrich, st. louis, MO (www.sigma-Aldrich. com)) was added to the reaction mixture. The reaction mixture was heated to 100 ℃ and heated to 100 ℃ for 16 hours. The solvent was then removed under reduced pressure to give a residue which was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (gradient eluent from 20: 80 ethyl acetate/hexane-10: 90 ethyl acetate/hexane) to give compound 14 as a yellow solid.

Identification of Compound 14 Using H¹NMR was used for confirmation.

Compound 14:

¹HNMR(CDCl₃)，8.21(1H，dd，J＝1.6，4.7Hz)，7.63(1H，dd，J＝1.6，7.8Hz)，7.40(1H，d，J＝0.5Hz)，7.18(2H，d，J＝0.5Hz)，6.89(1H，dd，J＝4.7，7.8Hz)，5.62(1H，br)，5.27(m，1H)，3.84(2H，t，J＝10.6Hz)，3.50(1H，dt，J＝2.9，15.3Hz)，3.08(1H，dd，J＝3.6，12.6Hz)，3.00(1H，dt，J＝3.3，15.3Hz)，2.44(3H，s)，1.48(3H，d，J＝7.2Hz)ppm.

(M+1)m/z：418.0.

5.10. example 10: synthesis of benzoxazole piperazine compound GIO

Compound 17(5g, 30.7mmol) and piperazine 2(3.1g, 30.7mmol) were dissolved in 18mL of DMSO and stirred at 100 ℃ for about 3 h. The reaction mixture was then cooled to room temperature and the solvent was removed under reduced pressure to give a mixture of compounds 18 and 19.

A solution of 6-fluoro-benzothiazol-2-ylamine 20(3.7g, 23.0mmol) in DCM (15mL) was added dropwise to the cooled solution of chloroformate 4. The resulting reaction mixture was stirred for 5 minutes, and then 10mL of triethylamine was added to the solution. The reaction mixture is then warmed to room temperature and concentrated under reduced pressure at about 40 ℃ to provide the compound of formula 21. The compound of formula 21 was dissolved in DCM (30mL) and the resulting solution was added to a solution of a mixture of compounds 18 and 19 prepared above in DCM (10 mL). The resulting reaction mixture was stirred for 5 minutes, and then the solvent was removed under reduced pressure to obtain a residue comprising the compound GIO and the benzoxazole piperazine compound of formula 22. The residue was purified by silica gel column eluting with 5: 95 ethyl acetate: hexane to give 0.69g of Compound GIO.

5.11.Example 11: binding of benzoxazole piperazine compounds to mGluR5

The following experiments can be applied to demonstrate that benzoxazole piperazine compounds bind to and modulate the activity of mGluR 5.

Cell culture: primary glial (cell) medium was prepared from the cortex of 18-day-old Sprague-Dawley (rat) embryos. The cortex is cut and then dissociated by grinding. The resulting cell homogenate was inoculated into Dulbecco's Modified Eagle's medium ("DMEM," pH7.4 ") in a T175 flask (BIOCOAT, available from Becton Dickinson and company Inc., Franklin Lakes, N.J.) precoated with poly-D-lysine, buffered with 25mM HEPES, and 15% fetal calf serum (" FCS, "available from Omaha, NE, Hyclone Laboratories Inc.), followed at 37 ℃ and 5% CO₂And (4) incubating. After 24 hours, the FCS addition was reduced to 10%. On day six, oligodendrocytes and lattice cells were removed by vigorously tapping the sides of the flask. One day after this purification step, a second generation of astrocyte medium was established by plating it directly in DMEM and 10% FCS in 96T 175 flasks (BIOCOAT) pre-coated with poly-D-lysine at a density of 65,000 cells/well. After 24 hours, the stars were washed with serum-free medium The cells were plated in DMEM without glutamate, with 0.5% FCS, 20mM HEPES, 10ng/mL epidermal growth factor ("EGF"), 1mM sodium pyruvate and 1 XPcillin/streptomycin at pH 7.5, 37 ℃ and 5% CO₂And culturing for 3 to 5 days. As per S.Miller et al Neuroscience 15 (9): 6103-6109(1995), which allows astrocytes to express mGluR5 receptor.

Experimental protocol: after 3-5 days of incubation with EGF, 127mM NaCl, 5mM KCl, 2mM MgCl at pH 7.4₂、700mM NaH₂PO₄、2mM CaCl₂、5mMNaHCO₃The astrocytes were washed with 8mM HEPES, 10mM glucose ("assay buffer"), and then loaded with the dye Fluo-4 using 0.1mL of assay buffer (final concentration 3mM) containing Fluo-4 (molecular probes Inc. available from Eugene, OR). After 90 minutes of dye loading (dye loading), the cells were washed twice with 0.2mL of assay buffer and suspended in 0.1mL of assay buffer. The plate containing the astrocytes was then transferred to a fluorescence imaging plate reader (available from molecular devices Corporation of Sunnyvale, CA) to determine calcium flux in the presence of glutamate and with or without antagonists. After monitoring the fluorescence profile for 15 seconds to establish a baseline, DMSO (dimethylsulfoxide) solutions containing different concentrations of the benzoxazole piperazine compounds diluted in assay buffer (0.05mL of 4X dilution as a competition curve) were added to the cell plate and the fluorescence profile was monitored for 2 minutes. 0.05mL of 4 Xglutamic acid solution (agonist) was then added to each well to give a final glutamic acid concentration of 10mM per well. The fluorescence pattern of the plate was monitored for an additional 60 seconds after addition of the agonist. The final concentration of the DMSO solution in this experiment was 1.0%. In each experiment, fluorescence was monitored as a function of time and data analysis was performed with microsoft excel and GraphPad Prism. Dose-response curves were fitted using curvilinear regression to determine IC ₅₀The value is obtained. In each experiment, each data point was measured twice. The results of the experiments will show that benzoxazole piperazine compounds bind to and modulate the activity of mGluR 5.

5.12.Example 12: preparation ofIn vivo experiments for prevention and treatment of pain

Laboratory animal: at the start of the experiment, rats weighing 200-260g were used for each experiment. Rats were housed in groups and were allowed free access to food and water at all times except for the 16 hours prior to oral administration of a benzoxazole piperazine compound. A control group was used as a control for rats treated with a benzoxazole piperazine compound. The vehicle of the benzoxazole piperazine compound was administered to the control group. The amount of the vehicle administered to the control group was the same as the amount of the benzoxazole piperazine compound and its vehicle administered to the test group.

Acute pain: the tail flick pain test (tail flick test) can be used to assess the effect of benzoxazole piperazine compounds in the treatment or prevention of acute pain. Rats were placed in a cotton bag and their tail was exposed to a radiant heat focused beam at 5cm from the tip of the tail using a tail flick unit (model 7360, available from Italy as ugobaile). Tail flick latency (tail flick latency) is defined as the time interval from the onset of thermal stimulation to the flick. Animals that did not respond within 15 seconds were removed from the tail flick pain apparatus and assigned a retraction latency of 15 seconds. Tail-flick latency was measured immediately before (before treatment) and 1, 3 and 6 hours after administration of the benzoxazole piperazine compound. Data are expressed as percent (% MPE) of tail flick latency (sec) and maximum possible efficacy (i.e., 15 sec) and are calculated as follows:

The tail flick pain test in rats is described in F.E.D' Amour et al, "A Method for determining Loss of pain sensing," J.Pharmacol. exp. Ther.72: 74-79(1941). The results will demonstrate that benzoxazole piperazine compounds are useful for treating or preventing acute pain.

Acute pain can also be assessed by determining paw withdrawal threshold ("PWT") to determine the animal's response to noxious mechanical stimuli, as described below.

Inflammatory pain: the Freund's complete adjuvant ("FCA") model of inflammatory pain can be used to assess the effect of the benzoxazole piperazine compounds in treating or preventing inflammatory pain. FCA-mediated Inflammation of the rat hind paw is associated with the development of hyperalgesia by a persistent inflammatory mechanism, which provides a reliable predictor of the anti-hyperalgesic effects of clinically used analgesics (L.Bartho et al, "invasion of Capsaicin-sensitive nerves in hyperalgesia and Enhanced ocular Inflammation in Inflammation," Nauyn-Schmiedberg's Archives of Pharmacology342: 666-670(1990)). 50 μ L of 100% FCA was administered by injection to the bottom of the left hind paw of each animal. 24 hours after injection, animals were assessed for response to noxious mechanical stimuli by determining PWT as described below. Then, the rats are injected with 1, 3, 10 or 30mg/Kg of one benzoxazole piperazine compound or 30mg/Kg of indometacin or a carrier. Their response to noxious mechanical stimuli was measured 2, 4, 6 and 24 hours after injection. The percentage of hyperalgesia reversal per animal was defined as:

The results show that the benzoxazole piperazine compounds are useful for treating or preventing inflammatory pain.

Neuralgia of nerve: the use of the Seltzer model or Chung model to assess the effect of benzoxazole piperazine compounds in the treatment or prevention of neuropathic pain is useful.

In the Seltzer Model, a partial sciatic nerve ligation Model of neuropathic Pain was used to produce neuropathic hyperalgesia in Rats (Z. Seltzer et al, "A Novel biomedical Model of neuropathic Pain Disorders Produced in Rats by Partial Sciatic NerveInjury，”Pain43: 205-218(1990)). In isoflurane/O₂Left sciatic nerve partial ligation was performed under inhalation anesthesia. Following induction of anesthesia, the left thigh of the rat was shaved, the sciatic nerve was exposed to high femoral levels through a small incision, and then carefully separated from the surrounding connective tissue at a point proximal to the trochanter, i.e., distal to the point where the posterior biceps semitendinosus nerve branch separates from the common sciatic nerve. A 7-0 wire suture is inserted into the nerve and tied using an 3/8 curved reverse-cutting mini-needle, such that 1/3 to 1/2 of the nerve thickness is tied with the tie wire. The wound was closed with a single muscle suture (7-0 silk) and a Michelle forceps. After surgery, the antibiotic powder is scattered on the wound area. Sham-treated (Sham-treated) group rats underwent the same surgical procedure except that the sciatic nerve was not treated. After surgery, animals were weighed and placed on a warm pad until they recovered from anesthesia. The animals were then returned to their cages until the behavioral testing began. The response of the animals to noxious mechanical stimuli was assessed by measuring PWT immediately prior to and 1, 3 and 6 hours after administration via the left and right hind paws of the animals, as described below. The percent reversal of neuropathic hyperalgesia is defined as follows:

% reversal of 100- [ (PWT before right-PWT after left administration)/(PWT before right-PWT before left administration) ] x100

In the Chung model, the spinal nerve ligation model of neuropathic pain was applied to produce mechanical, thermal and tactile hyperalgesia in rats. In isoflurane/O₂Surgery was performed under inhalation anesthesia. After induction of anesthesia, at L₄-S₂A3 cm incision was made horizontally and the left paraspinal muscle was separated from the spinous process. Carefully remove the L with a small rongeur₆Transverse process to see L₄-L₆The spinal nerve. Will be left L₅(or L)₅And L₆) The spinal nerves were separated and tightly ligated with silk threads. Complete hemostasis is confirmed and the wound is then closed with non-absorbable sutures (e.g., nylon sutures) or stainless steel staples. Pseudo-processing (Sham-t)reactivated) group of rats underwent the same surgical procedure except that the spinal nerves were not treated. After surgery, animals were weighed, injected subcutaneously (s.c.) with saline or ringer's lactate, dusted with antibiotic powder over the wound area, and placed on a warm pad until they recovered from anesthesia. The animals were then returned to their cages until the behavioral testing began. Animals were assessed for response to noxious mechanical stimuli by measuring PWT, as described below, immediately prior to and 1, 3 and 5 hours after administration of the benzoxazole piperazine compound via the left and posterior paw of the animal. These animals were also evaluated for their response to noxious thermal stimuli or tactile hyperalgesia, as described below. Chung Model of neuropathic Pain is described in S.H.Kim, "An Experimental Model for PeripheralNeuropathy Produced by segmented Spinal Nerve activation in the Rat," Pain Nerve activation in the Rat 50(3): 355-363(1992). The results show that the benzoxazole piperazine compounds are useful for treating or preventing neuropathic pain.

Response to mechanical stimuli as an assessment of mechanical hyperalgesia: paw pressure experiments can be used to assess mechanical hyperalgesia. In this experiment, Stein, at "Universal Inflammation of the Hindpaw in rates as a Model of Prolongated Noxious Stimulation: alternations in Behavior and nociceptive thresholds, "Pharmacology Biochemistry and Behavior31: 451-455(1988), the hindpaw withdrawal threshold (PWT) for a noxious mechanical stimulus was determined using an analgesymeter (model 7200, Ugo Basile, Italy). The maximum weight applicable to the rat hind paw was designated 250g, while the endpoint was designated as the complete withdrawal of the paw. PWT was determined only once per rat at each time point and only affected (ipsilateral) paw was tested.

Response to thermal stimulus as an assessment of thermal hyperalgesia: thermal hyperalgesia can be assessed using a plantar test. In this test, Hargreaves et al, "A New and sensitive Method for Measuring thermal l Nociception in CutaneousHyperalgesia，”Pain 32(1): 77-88(1988), a hindpaw withdrawal threshold (PWT) for noxious thermal stimuli was determined using a plantar testing device (Ugo Basile available from Italy). The maximum exposure time was set at 32 seconds to prevent tissue damage, and paw withdrawal from any direct withdrawal from the heat source was set as the endpoint. The threshold was determined three times at each time point and then averaged. Only affected (ipsilateral) paw was tested.

Assessment of tactile hyperalgesia: rats were acclimatized for at least 15 minutes in a clear plexiglas compartment with a metal mesh floor for tactile hyperalgesia assessment. After acclimation, the left (operated) plantar surface of the foot of each rat was treated with a series of von Frey monofilaments. The series of von Frey monofilaments consists of six monofilaments of increasing diameter, the smallest diameter being the first to be made. Five tests were run with each filament, with each test being approximately 2 minutes apart. Each effect lasted 4-8 seconds, or until retraction behavior was observed as reflected by pain. Flinching, paw withdrawal or paw licking were considered behavioral responses due to the nociceptive response.

5.13.Example 13: in vivo experiments for prevention or treatment of anxiety

The elevation maze test (the elevated plus size test) or the shock-bar burying test (shock-probe burying test) can be used to evaluate the anxiolytic activity of benzoxazole piperazine compounds in rats or mice.

Plateau maze test: the plateau maze consists of a platform containing 4 arms, two of which are open and two of which are closed (50x10x50cm with one open top plate). The rat (or mouse) is placed in the center of the platform, at the intersection of the 4 arms, facing one of the closed arms. The time of stay in the open arm and in the closed arm and the number of entries into the open arm during the test were recorded. The test was performed before dosing and again after dosing.The test results are expressed as the average time in the open arm and the average number of entries into the open arm. Known anxiolytics increase the time and number of entries into the open arms. The plateau maze test is described in D.Treit, "Animal Models for the student Anti-anxiety Agents: a Review, "Neuroscience&BiobehavioralReviews 9(2)：203-222(1985)。

Burying Test of electric Shock rod (The Shock-Probe Burying Test) : the test equipment for the burying test of the electric shock rod consists of a plexiglass box of size 40x30x40cm, in which approximately 5cm of bedding (odor absorbing cat mat) is uniformly laid, and which has a small hole at one end through which a shock rod (6.5 cm long, 0.5cm diameter) can be inserted. Two copper wires are spirally wound on the organic glass lightning rod in advance, and current can be connected through the copper wires. The current was set to 2 mA. Rats were habituated to the test device by placing them in a box without shock rod inserted for 30 minutes each day for 4 consecutive days. On the test day, following dosing, rats were placed in one corner of the test box. The wand was not energised until the rat touched the test wand with the mouth or fore paw, and immediately the rat received a brief 2mA shock. Immediately after the rat receives its first shock, a 15 minute test period begins with the test bars remaining energized for the remainder of the test period. The shock elicits buried behavior in the rat (burying behavior). After the first shock, the time for the rat to broadcast or cover bedding in the direction of the wand with its mouth or fore paw (burying behavior) was measured and the number of shocks triggered by the touches received by the rat through the wand was recorded. Known anxiolytics reduce the number of burying behaviors in rats. Additionally, an indicator of the response of the rats to each shock was scored on a 4-scale. The total time spent immobile during the 15 minute test period was taken as an indicator of general activity. The shock rod burying test is described in d.treit, 1985, above. The results show that the benzoxazole piperazine compounds are useful for treating or preventing anxiety disorders.

5.14.Example 14: preventing or treatingIn vivo experiments for treating addiction disorders

Habitual site preference tests (The conditioned place preference test) or drug self-administration tests (drug self-administration test) can be used to assess The ability of benzoxazole piperazine compounds to attenuate The dependence of known drugs of abuse.

Habitual place preference test: the apparatus for testing habitual site preferences consisted of two large wooden compartments (45x45x30cm) with a front wall of plexiglass. The two large wooden compartments are significantly different. The door behind each large compartment leads to a small box (36x18x20cm) made of wood painted grey with wire mesh ceiling. The two large compartments differ in many ways: shading (white vs black), illumination level (plexiglas door in white compartment covered with aluminum foil with only 7x7cm window), structure (white compartment with 3cm thick floor (40x40cm), nine holes of 5cm diameter equally spaced, while black compartment with wire mesh floor), and olfactory signature (cue) (saline in white compartment and 1mL 10% acetic acid in black compartment). On the acclimation and testing days, the door to the small box remained open, leaving the rat free access to the two large compartments.

The first time the rat is placed in the compartment is an acclimation period, and the door to the smaller ash box remains open, leaving the rat free access to the two large compartments. During the acclimation period, rats generally do not show a preference for which compartment. After the acclimation period, the rats were given 6 conditioning periods (sessions). The rats were divided into 4 groups: vehicle pretreatment + vehicle (control group), 2-pyrimidylpiperazine compound pretreatment + vehicle, vehicle pretreatment + morphine, 2-pyrimidylpiperazine compound pretreatment + morphine. Rats were injected with one of the drug combinations for each conditioning period and confined in one compartment for 30 minutes. On the following day, rats received a vehicle + vehicle treatment and were confined to another compartment. Each rat received three conditioning periods consisting of 3 drug combination-compartments and 3 vehicle-compartment pairs. The order of injections and drug/compartment pairs were balanced between groups. On the test day, rats were injected with morphine or vehicle prior to testing (30 minutes to 1 hour) and placed in the device with the door to the ash box left open, allowing the rats to freely probe the entire device for 20 minutes. The residence time in each compartment was recorded. During the testing period, known drugs of abuse increase the residence time in the drug paired compartment. If the benzoxazole piperazine compound blocks the execution of preference for morphine habit site (reward), the time taken by rats pre-treated with benzoxazole piperazine compound will not differ on each side, and the group will not differ in two compartments from the group of rats given vehicle + vehicle. The time spent in each compartment (drug pair combination versus vehicle pair) data was analyzed. Generally, the experiment was repeated using a minimum of 3 doses of the benzoxazole piperazine compound.

Drug self-administration test: the instrument used for the drug self-administration test is a standard commercially available conditioned reflex cassette (chamber). Before the drug test began, rats were trained to press a control stick for food reward. After stable compression bar behavior became habituated, rats were tested for habituation of compression bars to receive drug rewards. Rats were implanted with a long-term indwelling jugular catheter to administer the compound intravenously and allowed to recover 7 days before training began. The experimental period was 5 days, 3 hours per day. Rats are trained to self-administer a known drug of abuse, such as morphine. The rats were then provided with two control levers, an "active" lever and a "passive" lever. Pressing the positive lever results in the dosing on a fixed ratio 1(FR1) schedule (i.e. one injection of the plunger) followed by a 20 second pause period (signaled by the light on the top of the lever). Pressing the passive lever results in administration of the vehicle. Training was continued until the total morphine injections stabilized within ± 10% of each phase (total). Trained rats were then used to evaluate the effect of the benzoxazole piperazine compound pretreatment on self-administration. On the test day, rats were pretreated with a benzoxazole piperazine compound or excipient and then allowed to self-treat as usual I administer the drug. If the benzoxazole piperazine compound blocks the rewarding effect of morphine, rats pretreated with the benzoxazole piperazine compound will show a lower response rate compared to their previous response rate and rats pretreated with vehicle. Data analysis was performed for changes in the number of drug infusions per test period (number of drug infusions for test period-number of drug infusions for training period). The results will demonstrate that benzoxazole piperazine compounds are useful for the treatment or prevention of an addictive disorder.

5.15.Example 15: functional assays for demonstrating mGluR1 antagonistic properties

Functional assays that exhibit mGluR1 antagonistic properties are well known in the art. For example, the following program test may be applied.

A CHO-rat mGluR1 cell line (M.Masu and S.Nakanishi, Nature 349: 760-765(1991)) was generated using cDNA-encoded rat mGluR1 receptors. The cDNA encodes the rat mGluR1 receptor, available, for example, from prof.s.nakanishi (Kyoto, Japan).

CHO-rat mGluR1 cells were plated at 40,000/well in a Costar 3409 black clear-bottom 96-well tissue culture treatment plate (Fisher Scientific available from Chicago, IL) and incubated for approximately 12 hours in Dulbecco's modified Eagle's medium (DMEM, pH7.4) supplemented with glutamine, 10% FBS, 1% penicillin/streptomycin, and 500. mu.g/mL Geneticin (Geneticin). CHO-rat mGluR1 cells were then washed and treated with Optimem medium (Invitrogen available from Carlsbad, Calif.), incubated for a period of 1 to 4 hours, and then loaded with the dye Fluo-4 (Molecular Probes Inc. available from Eugene, OR). After incubation, cells were loaded with loading buffer (127mM NaCl, 5mM KCl, 2mM MgCl) ₂、700μM NaH₂PO₄、2mM CaCl₂、5mM NaHCO₃8mM HEPES and 10mM glucose, pH7.4) and then incubated with 3. mu.M Fluo-4 in 0.1mL of loading buffer for 90 minutes. The cells were then washed twice with 0.2mL of loading buffer, resuspended in 0.1mL of loading buffer, and transferredThe flux of calcium flux was measured in the presence of glutamic acid and with or without a benzoxazole piperazine compound by moving to a Fluorometric Imaging Plate Reader (FLIPR) (available from Molecular Devices Corp. of Sunnyvale, Calif.).

To determine calcium flux, the fluorescence spectra were monitored for about 15 seconds to establish a baseline, DMSO (dimethylsulfoxide) solutions containing various concentrations (ranging from about 50 μ M to about 0.8nM) of the benzoxazole piperazine compounds in loading buffer (0.05mL of 4X dilution) were added to the cell plates, and the fluorescence spectra were monitored for about 2 minutes. 0.05mL of 4 Xglutamic acid solution (agonist) was then added to each well to provide a final concentration of 10. mu.M glutamic acid per well, and the fluorescence spectrum was monitored for about 1 minute. The final concentration of the DMSO (dimethyl sulfoxide) solution in this experiment was 1%. In each experiment, the fluorescence spectra were monitored as a function of time and IC was determined using curve regression ₅₀The value is obtained. In each experiment, each data point was measured twice.

5.16.Example 16: combination of benzoxazole piperazine compound and VR1

Methods for assaying compounds for their ability to inhibit VR1 are well known to those skilled in the art, for example, those methods are disclosed in U.S. Pat. No. 6,239,267 to Duckworth et al; McIntyre et al, U.S. Pat. Nos. 6,406,908; julius et al, U.S. patent No. 6,335,180. The results of this assay will demonstrate that benzoxazole piperazine compounds bind to VR1 and modulate its activity.

Binding of compound AAQ to VR 1: test protocol

Human VR1 clone. Human spinal cord RNA (purchased from Clontech, Palo Alto, Calif.) was used. Following its product description, 1.0. mu.g of total RNA was reverse transcribed using Thermoscript reverse transcriptase (available from Invitrogen, Carlsbad. CA) and oligo dT primers (oligo dT primers). The reverse transcription reaction was incubated at 55 ℃ for 1 hour, heat-inactivated at 85 ℃ for 5 minutes, and then treated with RNase (ribonuclease) H at 37 ℃ for 20 minutes.

The human VR1cDNA sequence was obtained by comparing the pre-annotated human genomic sequence to the published rat (genomic) sequence. The intron sequences were removed and flanking exon sequences were added to generate the predicted human cDNA. The coding region flanked by primers for human VR1 was designed as follows: forward primer (forward primer):

AAGATCTTCGCTGGTTGCACACTGGGCCACA, respectively; and reverse primer (reverse primer): GAAGATCTTCGGGGACAGTGACGGTTGGATGT are provided.

VR1 Polymerase Chain Reaction (PCR) was performed on one tenth of the reverse transcription reaction mixture using extended Long template polymerase (extended Long template polymerase) and extended Buffer 2 (extended Buffer 2) IN a final volume of 50 μ L according to the manufacturer's instructions (Roche Applied sciences. indianapolis, IN). After denaturation for 2 min at 94 ℃, a PCR amplification cycle was performed 25 times: amplification was completed at 94 ℃ for 15 seconds, at 58 ℃ for 30 seconds, at 68 ℃ for 3 minutes, followed by a final incubation at 72 ℃ for 7 minutes. Gel separation using 1.0% agarose, Tris-Acetate Gel containing 1.6. mu.g/mL crystal violet gave a 2.8kb PCR product and purified using a S.N.A.P. UV-Free Gel Purification Kit (available from Invitrogen). The PCR product of VR1 was cloned into pIND/V5-His-TOPO vector (commercially available from Invitrogen) according to the manufacturer's instructions. DNA preparation, restriction enzyme digestion, and preliminary DNA sequencing were performed according to standard protocols. Full-length sequencing confirmed the identity of human VR 1.

Generation of inducible cell lines. Unless otherwise indicated, cell culture reagents were purchased from Life Technologies, Rockville, Md. HEK293-EcR cells expressing ecdysone receptors (available from Invitrogen) were cultured in growth medium (Dulbecco's modified Eagles medium containing 10% fetal bovine serum (available from HYCLONE, Logan, UT), 1x penicillin/streptomycin, 1x glutamine, 1mM sodium pyruvate, and 400 μ g/ml zeocin (available from Invitrogen)). VR1-pIND constructs were transfected into HEK293-EcR cell lines using Fugene transfection reagent (available from Roche applied sciences, Basel, Switzerland). After 48 hours, the cells were transferred to selection medium (growth medium containing 300. mu.g/mLG 418 (available from Invitrogen)). After about 3 weeks, Zeocin/G418 resistant clones (resistant colloids) of the individual were isolated and expanded. The multiple clones were seeded in 96-well plates and their expression was induced for 48 hours in selective medium supplemented with 5 μ M ponasterone a ("PonA") (commercially available from Invitrogen) to identify functional clones. On the test day, cells were loaded with Fluo-4, a calcium sensitive dye available from Molecular Probes, Eugene, OR, and CAP-mediated calcium influx was measured using a fluorometric imaging reader ("FLIPR"), available from Molecular Devices corp. Functional clones were retested, amplified and cryopreserved.

pH based testing. Two days prior to performing this assay, cells were seeded at 75,000 cells/well on poly-D-lysine coated 96-well clear bottom blackboards (available from Becton-Dickinson) in growth medium containing 5 μ MPonA (available from Invitrogen) for inducible expression. On the day of testing, each plate contained 1.6mM CaCl at 0.2mL₂And 20mM HEPES, pH7.4 in 1x Hank's balanced salt solution (available from Life Technologies) ("Wash buffer") followed by loading with 0.1mL of Wash buffer containing Fluo-4 (final concentration 3. mu.M, available from Molecular Probes). After 1 hour, the cells were washed twice with 0.2mL of wash buffer and then in 0.05mL of buffer containing 3.5mM CaCl₂And 10mM citrate, pH7.4 in 1 XHank's balanced saline solution (commercially available from Life Technologies) ("test buffer") for resuspension. The plates were then transferred to a FLIPR (commercially available from Molecular Devices) for testing. Compound AAQ was diluted with test buffer, 50mL of the resulting solution was added to the cell plate, and the solution was monitored for two minutes. The final concentration of compound AAQ ranged from approximately 50pM to 3. mu.M. Agonist buffer (wash buffer titrated with 1N HCl to provide a solution of pH 5.5 when mixed 1: 1 with test buffer) was then added to each well (0.1mL) and the plates were incubated for an additional 1 min. All the time course is carried out Data were collected and analyzed in Excel and GraphPad Prism. IC of compound AAQ tested according to this protocol₅₀261.8 ± 75.1(n ═ 6).

Capsaicin (capsaicin) -based assay. Two days before performing this assay, cells were seeded in poly-D-lysine coated 96-well clear-bottom black panels (50,000 cells/well) containing 5 μ M PonA in growth medium (commercially available from Invitrogen) to induce expression. On the day of testing, each plate contained 1mM CaCl at 0.2mL₂And 20mM HEPES, pH 7.4 1x Hank's balanced salt solution (available from Life Technologies) washing, and with 0.1mL containing Fluo-4 (final concentration of 3M) washing buffer loading cells. After one hour, the cells were washed twice with 0.2mL of wash buffer and resuspended in 0.1mL of wash buffer. Each plate was then transferred to a FLIPR (available from Molecular Devices) for testing. 50 μ L of compound AAQ diluted in test buffer was added to each cell plate, followed by incubation for 2 minutes. The final concentration of compound AAQ ranged from approximately 50pM to 3. mu.M. Human VR1 was activated by the addition of 50. mu.L capsaicin (400nM) and plates were incubated for an additional 3 min. Data were collected over the course of all times and analyzed in Excel and GraphPadPrism. IC of compound AAQ tested according to this protocol ₅₀50.7 ± 14.7nM (n ═ 3).

The results of both the pH-based and capsaicin-based tests demonstrate that compound AAQ, an exemplary benzoxazole piperazine compound, binds to and modulates the activity of human VR1 and is therefore useful for the treatment and prevention of pain, UI (urinary incontinence), ulcers or IBS (irritable bowel syndrome).

The invention is not limited to the specific embodiments disclosed in the examples, which are intended as illustrations of a few aspects of the invention, and any functionally equivalent embodiments are within the scope of the invention. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art and are intended to be included within the scope of the appended claims.

Some references are cited herein, the entire contents of which are incorporated herein by reference.

Claims (30)

1. A compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein

Ar₁Is composed of

A is

R₁is-Cl, -Br, -I, - (C)₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

each R₃Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) IICycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C) ₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

R₄is-H or- (C)₁-C₆) An alkyl group;

each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₉Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each-halo is-F, -Cl, -Br or-I;

n is an integer of 0 to 3;

p is an integer of 0 to 2;

m is 0 or 1; and

x is 0 or 1.

2. The compound of claim 1, wherein Ar₁Is a pyridyl group.

3. The compound of any one of claims 1 or 2, wherein x is 1.

4. The compound of claim 3, wherein A is-C (O) N (R)₄)-。

5. The compound of any one of claims 1 or 2, wherein x is 0.

6. The compound of any one of claims 1-2, wherein n or p is 0.

7. The compound of any one of claims 1-2, wherein n or p is 1.

8. The compound of claim 1, wherein Ar₁Is a pyrimidinyl group.

9. The compound of claim 8, wherein x is 1 and A is-C (O) N (R)₄)-。

10. The compound of any one of claims 1 or 2, wherein:

R₁is-CH₃、-CF₃-Cl, -Br or-I;

m is 0;

n or p is 0;

x is 1;

a is-C (O) -N (R)₄)-；

R₄is-H;

R₈is-H; and

R₉is-CH₃、-CF₃、-OCH₂CH₃-tert-butyl, -Cl, -Br or-F.

11. The compound of claim 10, wherein R₁is-CH₃And R₉is-Cl, -Br or-F.

12. The compound of claim 10, wherein R₁is-Cl and R₉is-Cl, -Br or-F.

13. The compound of any one of claims 1 or 2, wherein:

R₁is-CH₃、-CF₃-Cl, -Br or-I;

m is 1;

R₃is- (C)₁-C₁₀) An alkyl group;

n or p is 0;

x is 1;

a is-C (O) -N (R)₄)-；

R₄is-H;

R₈is-H; and

R₉is-CH₃、-CF₃、-OCH₂CH₃-tert-butyl, -Cl, -Br or-F.

14. The compound of claim 13, wherein R₃is-CH₃。

15. The compound of claim 13, wherein R₃To the linkage-C (O) -N (R)₄) -the nitrogen atoms of the group are attached to adjacent carbon atoms.

16. The compound of claim 15, wherein R₁is-CH₃，R₃is-CH₃And R₉is-Cl, -Br or-F.

17. The compound of claim 15, wherein R ₁is-Cl, R₃is-CH₃And R₉is-Cl, -Br or-F.

18. The compound of any one of claims 13, wherein R₃The carbon atom attached is in the (R) configuration.

19. The compound of claim 1, wherein m is 1 and R₃The carbon atom attached is in the (R) configuration.

20. A compound according to claim 1 selected from:

and pharmaceutically acceptable salts thereof.

21. A compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein

Ar₁Is composed of

Ar₂Is composed of

R₁Is-halo, - (C)₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered)) Heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

R₃is-H or-CH₃：

Each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C) ₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₉Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, -C (halo)₃-CH (halo)₂、-CH₂(halo), -OC (halo)₃-OCH (halo)₂、-OCH₂(halo), -CN, -OH, -halo, -N₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each-halo is-F, -Cl, -Br or-I;

n is an integer of 0 to 3; and

p is an integer of 0 to 2.

22. A compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein

Ar₁Is composed of

Ar₂Is composed of

A is

R₁Is-halo, - (C)₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R ₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

R₃is-CH₃；

R₄is-H or- (C)₁-C₆) An alkyl group;

each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₉Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, -C (halo)₃-CH (halo)₂、-CH₂(halo), -OC (halo)₃-OCH (halo)₂、-OCH₂(halo), -CN, -OH, -halo, -N₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each-halo is-F, -Cl, -Br or-I;

n is an integer of 0 to 3;

p is an integer of 0 to 2; and

x is 0 or 1.

23. A composition comprising a compound or a pharmaceutically acceptable salt of the compound of any one of claims 1-20 and a pharmaceutically acceptable carrier.

24. A composition, comprising:

(i) an effective amount of a compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein

Ar₁Is composed of

Ar₂Is composed of

R₁Is-halo, - (C)₁-C₆) Alkyl, -NO₂、-CN、-OH、-OCH₃、-NH₂-C (halo)₃-CH (halo)₂or-CH₂(halo);

each R₂Independently are:

(a) -halo, -CN, -OH, -O (C)₁-C₆) Alkyl, -NO₂or-NH₂；

(b)-(C₁-C₁₀) Alkyl, - (C)₂-C₁₀) Alkenyl, - (C)₂-C₁₀) Alkynyl, - (C)₃-C₁₀) Cycloalkyl, - (C)₈-C₁₄) Bicycloalkyl, - (C)₈-C₁₄) Tricycloalkyl, - (C)₅-C₁₀) Cycloalkenyl, - (C)₈-C₁₄) Bicycloalkenyl, - (C)₈-C₁₄) Tricycloalkenyl, - (3 to 7-membered) heterocycle or- (7 to 10-membered) bicycloheterocycle, each of which is unsubstituted or substituted with one or more R₅Substituted by groups; or

(c) -phenyl, -naphthyl, - (C)₁₄) Aryl or- (5-to 10-membered) heteroaryl, each of which is unsubstituted or substituted by one or more R₆Substituted by groups;

R₃is-H or-CH₃；

Each R₅Independently is-CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₆Independently is- (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃-CH (halo)₂、-CH₂(halo), -CN, -OH, -halo, -N₃、-NO₂、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each R₇Independently is-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C) ₅-C₈) Cycloalkenyl, -phenyl, - (C)₃-C₅) Heterocycle, -C (halo)₃、-CH₂(halo) or-CH (halo)₂；

R₈And R₉Are each independently-H, - (C)₁-C₆) Alkyl, - (C)₂-C₆) Alkenyl, - (C)₂-C₆) Alkynyl, - (C)₃-C₈) Cycloalkyl, - (C)₅-C₈) Cycloalkenyl, -phenyl, -C (halo)₃-CH (halo)₂、-CH₂(halo), -OC (halo)₃-OCH (halo)₂、-OCH₂(halo), -CN, -OH, -halo, -N₃、-N(R₇)₂、-CH＝NR₇、-NR₇OH、-OR₇、-COR₇、-C(O)OR₇、-OC(O)R₇、-OC(O)OR₇、-SR₇、-S(O)R₇or-S (O)₂R₇；

Each-halo is-F, -Cl, -Br or-I;

n is an integer of 0 to 3; and

p is an integer of 0 to 2; and

(ii) a pharmaceutically acceptable carrier or excipient.

25. Use of an effective amount of a composition or compound of any one of claims 1-24, or a pharmaceutically acceptable salt of the compound, in the manufacture of a medicament for treating or preventing a disorder selected from the group consisting of pain, urinary incontinence, ulcers, irritable bowel syndrome, inflammatory bowel disease, addiction, parkinson's disease, parkinson's syndrome, anxiety, epilepsy, stroke, seizure, pruritus, psychosis, cognitive disorders, memory deficits, restricted brain function, huntington's chorea, amyotrophic lateral sclerosis, retinopathy, muscle spasm, migraine, emesis, movement disorders, or depression in an animal.

26. Use of an effective amount of a composition or compound of any one of claims 1-24, or a pharmaceutically acceptable salt of the compound, in the manufacture of a medicament for treating or preventing a disease selected from pain, urinary incontinence, an ulcer, allergic large bowel syndrome, or an inflammatory bowel disease in an animal.

27. Use of an effective amount of the composition or compound of any one of claims 1-24, or a pharmaceutically acceptable salt of said compound, in the manufacture of a medicament for inhibiting VR1 in a cell.

28. A kit comprising a container containing an effective amount of the composition or compound of any one of claims 1-24 or a pharmaceutically acceptable salt of said compound.

29. A method of making a composition comprising the step of admixing a compound or a pharmaceutically acceptable salt of the compound of any one of claims 1-22.

30. A method of inhibiting VR1 function in a cell, comprising contacting a cell capable of expressing VR1 in vitro with an effective amount of the composition or compound of any one of claims 1-24 or a pharmaceutically acceptable salt of the compound.