RU2009119919A - NEW CHROMEN-2-ONE DERIVATIVES AND THEIR APPLICATION AS REVERSE INHIBITORS FOR MONOAMINE NEUROMEDIATORS - Google Patents

Abstract

 1. The compound of Formula I! . ! any of its stereoisomers or any mixture of its stereoisomers,! or a pharmaceutically acceptable salt thereof,! where Q is a chromen-2-one-yl group; ! wherein said chromen-2-one-yl group is substituted with one heteroaryl group; ! wherein said heteroaryl group is optionally substituted with one or more substituents independently selected from the group consisting of! halo, trifluoromethyl, trifluoromethoxy, cyano, amino, nitro, hydroxy, alkoxy, cycloalkoxy, methylenedioxy, ethylenedioxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl; ! and the chromen-2-one-yl group is optionally further substituted with one or more substituents independently selected from the group consisting of! halo, trifluoromethyl, trifluoromethoxy, cyano, amino, nitro, hydroxy, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl; ! R1 represents hydrogen or alkyl; ! wherein said alkyl is optionally substituted with one or more substituents independently selected from the group consisting of! halo, trifluoromethyl, trifluoromethoxy, cyano, amino, nitro, hydroxy, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl. ! 2. The chemical compound according to claim 1, where! R1 represents hydrogen or alkyl. ! 3. The chemical compound according to claim 1, where! Q represents a substituted chromen-2-one-7-yl group. ! 4. The chemical compound according to claim 1, where! Q represents a 3- (optionally substituted heteroaryl) -chromen-2-one-yl group. ! 5. The chemical compound according to claim 1, where! Q is chromen-2-one-7-yl substituted with a furanyl or benzofuranyl group. ! 6. Chemical compound

Claims (13)

1. The compound of Formula I

. any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof, where Q is a chromen-2-one-yl group; wherein said chromen-2-one-yl group is substituted with one heteroaryl group; wherein said heteroaryl group is optionally substituted with one or more substituents independently selected from the group consisting of halo, trifluoromethyl, trifluoromethoxy, cyano, amino, nitro, hydroxy, alkoxy, cycloalkoxy, methylenedioxy, ethylenedioxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl; and the chromen-2-one-yl group is optionally further substituted with one or more substituents independently selected from the group consisting of halo, trifluoromethyl, trifluoromethoxy, cyano, amino, nitro, hydroxy, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl; R ¹ represents hydrogen or alkyl; wherein said alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halo, trifluoromethyl, trifluoromethoxy, cyano, amino, nitro, hydroxy, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl. 2. The chemical compound according to claim 1, where R ¹ represents hydrogen or alkyl. 3. The chemical compound according to claim 1, where Q represents a substituted chromen-2-one-7-yl group. 4. The chemical compound according to claim 1, where Q represents a 3- (optionally substituted heteroaryl) -chromen-2-one-yl group. 5. The chemical compound according to claim 1, where Q is chromen-2-one-7-yl substituted with a furanyl or benzofuranyl group. 6. The chemical compound according to claim 1, which is a exo-7 - [(1S, 3S, 5R) - (8-aza-bicyclo [3.2.1] oct-3-yl) oxy] -3-furan-2-yl-chromen-2-one; exo-7 - [(1S, 3S, 5R) - (8-aza-bicyclo [3.2.1] oct-3-yl) oxy] -3-furan-3-yl-chromen-2-one; exo-7 - [(1S, 3S, 5R) - (8-aza-bicyclo [3.2.1] oct-3-yl) oxy] -3-benzofuran-2-yl-chromen-2-one; or a pharmaceutically acceptable salt thereof. 7. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to any one of claims 1 to 6, any of its stereoisomers or any mixture of its stereoisomers or its pharmaceutically acceptable salt, together with at least one pharmaceutically acceptable carrier, excipient or diluent. 8. The use of a chemical compound according to any one of claims 1 to 6, any of its stereoisomers or any mixture of its stereoisomers or its pharmaceutically acceptable salt for the manufacture of a medicament. 9. The use of claim 8 for the manufacture of a pharmaceutical composition for treating, preventing or alleviating a disease, or disorder, or condition of a mammal, including a human, that is sensitive to inhibition of reuptake of monoamine neurotransmitters in the central nervous system. 10. The use according to claim 9, where the disease, disorder or condition is a mood disorder, depression, atypical depression, depression due to pain, major depressive disorder, dysthymic disorder, bipolar disorder, bipolar disorder type I, bipolar disorder type II, cyclotymic disorder , mood disorder due to a general medical condition, substance-induced mood disorder, pseudo-dementia, Ganser syndrome, obsessive-compulsive dissolution swarm, panic disorder, panic disorder without agoraphobia, panic disorder with agoraphobia, agoraphobia without panic disorder in history, panic attack, memory impairment, memory loss, attention deficit hyperactivity disorder, obesity, anxiety, generalized anxiety disorder, eating disorder Parkinson's, parkinsonism, dementia, age-related dementia, senile dementia, Alzheimer's disease, Down syndrome, complex acquired immunodeficiency syndrome-dementia, dysfunction memory when aging, specific phobia, social phobia, social anxiety disorder, post-traumatic stress disorder, acute stress disorder, chronic stress disorder, drug dependence, drug abuse, addiction to drugs, cocaine abuse, nicotine abuse, tobacco abuse, alcohol addiction , alcoholism, kleptomania, withdrawal symptoms caused by cessation of substances, cause their dependence, pain, chronic pain, inflammatory pain, neuropathic pain, diabetic neuropathic pain, migraine pain, tension headache, chronic tension headache, pain associated with depression, fibromyalgia, arthritis, osteoarthritis, rheumatoid arthritis, back pain, cancer pain, irritable bowel pain, irritable bowel syndrome, postoperative pain, pain after mastectomy (PMPS), pain after stroke, drug-induced neuropathy, diabetic nev opathy, sympathetically supported pain, trigeminal neuralgia, toothache, muscle-facial pain, phantom pain, bulimia, premenstrual syndrome, premenstrual dysphoric disorder, late luteal phase syndrome, post-traumatic syndrome, chronic fatigue syndrome, chronic vegetative state, urinary incontinence, stress urinary incontinence, urgent urinary incontinence, bedwetting, sexual dysfunction, premature ejaculation, difficulty in erection, erectile dysfunction, premature female orgasm, tired leg syndrome, recurrent motor limb disorder, eating disorders, anorexia nervosa, sleep disorders, deep developmental disorders, autism, Asperger syndrome, Rett syndrome, childhood disintegrative disorder, learning disabilities, motor disorders, mutism, trichotillomania, narcolepsy, post-stroke depression, stroke-induced brain damage, stroke-induced neuronal damage, Gilles de la Tourette syndrome, tinnitus, ticose disorders, dysmo rficheskih disorders of the body, causing opposition disorder or disability after a stroke. 11. A method of treating, preventing or alleviating a disease, or disorder, or condition of an organism of a living animal, including a person, which is sensitive to inhibiting the reuptake of neurotransmitters monoamines in the central nervous system, comprising the stage of introducing into such an organism a living animal in need thereof an effective amount of a compound according to any one of claims 1 to 6, or any of its stereoisomers, or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof. 12. The compound according to any one of claims 1 to 6, any of its stereoisomers, or any mixture of its stereoisomers, or its pharmaceutically acceptable salt for use as a medicine. 13. The compound according to any one of claims 1 to 6, any of its stereoisomers, or any mixture of its stereoisomers, or its pharmaceutically acceptable salt for use in treating, preventing or alleviating a disease, or disorder, or condition of a mammal, including a human being sensitive to inhibition of reuptake of monoamine neurotransmitters in the central nervous system.