MXPA97009509A

MXPA97009509A - Therapeutic agents

Info

Publication number: MXPA97009509A
Application number: MXPA/A/1997/009509A
Authority: MX
Inventors: Kerrigan Frank; Crawford Cheetham Sharon; Victor Davies Roy
Original assignee: Knoll Aktiengesellschaft
Priority date: 1995-07-01
Filing date: 1997-12-04
Publication date: 1998-10-15

Abstract

Compounds of the formula I: wherein: A is S (O) pu O; p is 0, 1 or 2; g is 0, 1, 2, 3 or 4, n is 2 or 3, and R1, R2, R3, R4 and R5, are optional substituents, these compounds have utility in the treatment of disorders of the Central Nervous System, for example depression, anxiety, psychosis (for example schizophrenia), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, cerebral ischemia, obsessive-compulsive behavior, panic attacks, social phobias, eating disorders and anorexia, diabetes mellitus not dependent on insulin, hyperglycemia, or obesity

Description

THERAPEUTIC AGENTS The present invention relates to certain novel dihydroimidazole [2, lb] thiazole and dihydro-5H-thiazolo [3,2, a] pyrimidine substituted compounds, which have affinity for 5-HT? neuronal reuptake of 5-hydroxytryptamine and / or ñoradrenaline, to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of disorders of the Central Nervous System, for example depression, anxiety, psychosis (such as schizophrenia) ), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, cerebral ischemia, obsessive-compulsive behavior, panic attacks, social phobias, eating disorders and anorexia, dependent diabetes mellitus no insulin, hypoglicemia and stress.

Sharpe C. J. and Shadboit R. S. disclose certain dihydroimidazo [2, 1-b] thiazole compounds having antidepressant activity, Journal of Medicinal Chemistry, 1971, Vol. 14, No. 10, p 977-982. However, the document also notes that these compounds are generally less active and more toxic than the imidazolines, also described in the document. The compounds of the present invention are not disclosed or suggested herein.

The present invention provides compounds of the formula I: which include their pharmaceutically acceptable salts, wherein: A is S (0) p or O; p is 0, 1 and 2; g is O, 1, 2, 3 or 4; n is 2 or 3; Ri is a) halogen, b) an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, c) an alkoxy group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, d) an alkylthio group, an alkylsulfinyl group or an alkylsulfonyl group, each having 1 to 3 carbon atoms, optionally substituted by one or more halogens, e) hydroxy, f) an acyloxy group containing 1 to 3 carbon atoms, g) a hydroxyalkyl group containing 1 to 3 carbon atoms, h) cyano, i) an alkanoyl group containing 1 to 6 carbon atoms, j) an alkoxycarbonyl group containing 2 to 6 carbon atoms, k) a group carbamoyl or a carbamoylmethyl group, each optionally N-substituted by one or two alkyl groups, which contain 1 to 3 carbon atoms, 1) a sulfamoyl or sulfamoylmethyl group, each optionally N-substituted by one or two alkyl groups, each with 1 to 3 carbon atoms or pi) an amino group, optionally substituted by one or two alkyl groups, each having 1 to 3 carbon atoms; R ^, which are the same or different, when g is 2, 3 or 4; 12 'R3 and R4- independently, are H or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens; and R5 is a) halogen, b) an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, c) an alkoxy group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens , d) is an alkylthio group, an alkylsulfinyl group or an alkylsulfonyl group, each having 1 to 3 carbon atoms, optionally substituted by one or more halogens, e) hydroxy, f) an acyloxy group containing 1 to 3 carbon atoms, carbon, g) a hydroxyalkyl group having 1 to 3 carbon atoms, h) cyano, i) an alkanoyl group containing 1 to 6 carbon atoms, j) an alkoxycarbonyl group containing 2 to 6 carbon atoms, k) a carbamoyl group or a carbamoylmethyl group, each, optionally, N-substituted by one or two alkyl groups, each having 1 to 3 carbon atoms, 1) a sulfamoyl or sulfamoylmethyl group, each, optionally, N-substituted by one or two alkyl groups, each with 3 carbon atoms, m) an amino group, optionally substituted by one or two alkyl groups, each having 1 to 3 carbon atoms or n) is H. In a group of compounds of the formula I, A is S (0) p or O; p is 0, 1 or 2; g is 0, 1, 2, 3 or 4; n is 3; R; L is a) halogen, b) an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, c) an alkoxy group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, d) an alkylthio group, an alkylsulfinyl group or an alkylsulfonyl group, each having 1 to 3 carbon atoms, optionally substituted by one or more halogens, e) hydroxy, f) an acyloxy group containing 1 to 3 carbon atoms, carbon, g) a hydroxyalkyl group containing 1 to 3 carbon atoms, h) cyano, i) an alkanoyl group containing 1 to 6 carbon atoms, j) an alkoxycarbonyl group containing 2 to 6 carbon atoms, k) a carbamoyl group or a carbamoylmethyl group, each, optionally, N-substituted by one or two alkyl groups, each having 1 to 3 carbon atoms, 1) a sulfamoyl or sulfamoylmethyl group, each optionally N-substituted by one or two alkyl groups, each with 1 to 3 carbon atoms om) an amino group, optionally substituted by one or two alkyl groups, each having 1 to 3 carbon atoms; R- ^ are the same or different groups when g is 2, 3 or 4; R2, R3 and R4 are, independently, H or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens; and R3 is H, halogen or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens. In the preferred compounds in this group, A is S (0) p or 0; p is 0, g is 0 or 1; n is 3; R is halogen, an alkoxy group containing 1 to 3 carbon atoms or cyano; and R2 R3 4 and R5 are all H. In particularly preferred compounds in this group, A is S (0) p or O; p is 0, g is O, n is 3; and R2 R3 R4 and R5 are all H. In a group of preferred compounds of formula I, A is S (0) p; p is 0, 1 or 2; g is 0, 1, 2, 3 or 4; b is 2, is a) halogen, b) an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, c) an alkoxy group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, d) an alkylthio group, an alkylsulfinyl group or a sulkylsulfonyl group, each having 1 to 3 carbon atoms, optionally substituted by one or more halogens, e) hydroxy, f) an acyloxy group containing 1 to 3 atoms carbon, g) a hydroxyalkyl group containing 1 to 3 carbon atoms, h) cyano, i) an alkanoyl group containing 1 to 6 carbon atoms, j) an alkoxycarbonyl group containing 2 to 6 carbon atoms, ) a carbamoyl group or a carbamoylmethyl group, each, optionally, N-substituted by one or two alkyl groups, each having 1 to 3 carbon atoms, 1) a sulfamoyl or sulfamoylmethyl group, each, optionally, N-substituted by one or two alkyl groups, each with 1 to 3 carbon atoms or or m) an amino group, optionally substituted by one or two alkyl groups, each having 1 to 3 carbon atoms; ^ are identical or different groups when g is 2, 3 or 4; R2, R3 and R4, independently, are H or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens; and T5 is H, halogen or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens. Preferably, p is 0. In more preferred compounds in this group, p is 0; g is 0 or l; R? is halogen, an alkoxy group containing 1 to 3 carbon atoms or cyano; R2, R3, R4 are all H; and n is 2. In particularly preferred compounds in this group, p is O; g is O or 1; Ri is halogen, an alkoxy group containing 1 to 3 carbon atoms, or cyano, R2, R3, R4 and R5 are all H; n is 2; and when g is 1, the substituent ^ is in position 5 of the benzo ring system [b [thiophene. In especially preferred compounds of this group, p is 9; n is 2; g is 0 or 1; R2, R3, R4 and R5 are all H; and when g is 1, Ri is chlorine, fluorine, methoxy or cyano. More preferably, in compounds in this group where p is 0; n is 2, g is 0 or 1; R2, R3, R4 and R5 are all H; and when g is 1, the substituent R is in the 5-position of the benzo [b] thiophene ring system. In another group of preferred compounds of the formula I, A is 0; g is 0, 1, 2, 3 or 4; n is 2; Ri is a) halogen, b) an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, c) an alkoxy group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens , d) an alkylthio group, an alkylsulfinyl group or an alkylsulfonyl group, each having 1 to 3 carbon atoms, optionally, substituted by one or more halogens, e) hydroxy, f) an acyloxy group, with 1 to 3 carbon atoms, carbon, g) a hydroxyalkyl group containing 1 to 3 carbon atoms, h) cyano, i) an alkanoyl group containing 1 to 6 carbon atoms, j) an alkoxycarbonyl group containing 2 to 6 carbon atoms, k) a carbamoyl group or a carbamoylmethyl group, each, optionally, N-substituted by one or two alkyl groups, each having 1 to 3 carbon atoms, 1) a sulfamoyl or sulfamoylmethyl group, each, optionally, N-substituted by no or two alkyl groups, each with 1 to 3 carbon atoms om) a amino group, optionally substituted by one or two alkyl groups, each with 1 to 3 carbon atoms; Ri are the same or different groups when g is 2, 3 6 4; R2, R3 and R4, independently, are H or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens; and R5 is H, halogen or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or halogen radicals. In more preferred compounds in this group, n is 2, g is 0 or 1; Ri is halogen, an alkoxy group containing 1 to 3 carbon atoms or cyano; R2, R3, R4 and R5 are all H; and n is 2. In particularly preferred compounds in this group, n is 2; g is 0 or 1; is halogen, an alkoxy group containing 1 to 3 carbon atoms or cyano; R2, R3, R4 and R5 are all H; n is 2; and when g is l, the substituent Ri is in the 5-position of the benzo [b] furan ring system. In especially preferred compounds of this group, n is 2; R2, R3, R4 and R5 are all H; and g is 0.

The compounds of the formula I can exist as salts with pharmaceutically acceptable acids. Examples of such salts include hydrochlorides, hydrobromides, sulfates, methanesulfonates, nitrates, maleates, acetates, citrates, fumarates, tartrates (for example (+) - tartrates, (-) - tartrates or their mixtures, including racemic mixtures), succinates, benzoates and salts with amino acids, such as glutamic acid Compounds of the formula I and their salts may exist in the form of solvates (for example hydrates) Certain compounds of the formula I contain one or more chiral centers and there are in different active forms When the compounds of the formula I contain a chiral center, the compounds exist in two enantiomeric forms and the present invention includes both the enantiomers and mixtures of these enantiomers.The enantiomers can be resolved by methods known to those skilled in the art. the matter, for example by the formation of diastereoisomeric salts, which may be desired, for example, by crystallization; diastereoisomeric erivatives or complexes that can be separated, for example, by crystallization, gas-liquid or liquid chromatography; or gas-liquid or liquid chromatography in a chiral environment, for example on a chiral support, for example silica with a bound chiral ligand or in the presence of a chiral solvent. It will be appreciated that when the desired enantiomer is converted to another chemical entity by one of the separation methods described above, a further step is required to release the desired enantiomeric form. Alternatively, specific enantiomers can be synthesized by asymmetric synthesis using optically active reagents, substrates, catalysis or solvents, or by converting one enantiomer into the other by asymmetric transformation. When a compound of formula I contains more than one chiral center, it can exist in the diastereoisomeric forms. The diastereoisomeric pairs can be separated by methods known to those skilled in the art, for example by chromatography or crystallization and the individual enantiomers within each pair can be separated as described above. The present invention includes each diastereomer of compounds of formula I and mixtures thereof. Certain compounds of the formula I may exist in different tautomeric forms or as different geometric isomers, and the present invention includes each tautomeric and / or geometric isomer of the compounds of the formula I and mixtures thereof.

Certain compounds of the formula I can exist in different stable conformations that can be separated. For example, if R4 and / or R5 are bulky groups, there may be a restricted rotation around one or more links, due to steric obstruction. The torsional asymmetry is due to the restricted rotation around a single asymmetric bond, for example, because the steric obstruction or ring stress, can allow the separation of different conformations. The present invention includes each conformational isomer of the compounds of the formula I and mixtures thereof. Certain compounds of the formula I and their salts may exist in more than one crystalline form and the present invention includes each crystalline form and mixtures thereof. Certain compounds of the formula I and their salts may also exist in the form of solvates, for example hydrates, and the present invention includes each solvate and its mixtures. It will be understood that the compounds of the formula I in which g is 0, the substituent Ri is not present and all the substitution positions in the benzene ring are occupied by H. It will also be understood that the Ph symbol used in the formulas represents phenyl and Me represents methyl. Specific compounds of formula I are: 3- (benzo [b] thiophen-3-yl) -5,6-dihydroimidazo [2, 1-b] thiazole; 3- (benzo [b] thiophen-3-yl) -6,7-dihydro-5H-thiazolo [3,2- a] pyrimidine; 3- (benzo [b] furan-3-yl) -5,6-dihydroimidazo [2, 1-b] thiazole; 3- (benzo [b] furan-3-yl) -6,7-dihydro-5H-thiazolo [3,2-a] -pyrimidine; 3- (5-chlorobenzo [b [thiophen-3-yl] -5,6-dihydroimidazo [2, 1-b] thiazole; 3- (5-methoxybenzo [b] thiophen-3-yl) -5,6-dihydroimidazo [2, 1-b] thiazole; 3- (5-fluorobenzo [b] thiophen-3-yl) -5,6-dihydroimidazo [2, 1-b] thiazole 3- (5,6-dihydroimidazo [2, lb] thiazol-3-yl) benzo [ b] thiophene-5-carbonitrile; and their pharmaceutically acceptable salts. The present invention also includes pharmaceutical compositions comprising a therapeutically effective amount of a compound of formula I or its salts, together with a pharmaceutically acceptable diluent or carrier. As used herein, the term "active compound" denotes a compound of formula I or a salt thereof. In therapeutic use, the active compound can be administered orally, rectally, parenterally or topically, preferably orally. Thus, the therapeutic compositions of the present invention can take the form of any of the known pharmaceutical compositions for oral, rectal, parenteral or topical administration. Pharmaceutically acceptable carriers, suitable for use in the compositions, are well known in the art of pharmacy. The compositions of the invention may contain from 0.1 to 99% by weight of the active compound. The compositions of the invention < they are generally prepared in the form of a unit dose. Preferably, the unit dose of the active ingredient is from 1 to 500 mg. The excipients used in the preparation of these compositions are the excipients known in the art of pharmacy. The compositions for oral administration are the preferred compositions of the invention and they are the known dosage forms for such administration, for example, tablets, capsules, syrups and aqueous or oil suspensions. The excipients used in the preparation of these compositions are the excipients known in the art of pharmacy. The tablets can be prepared by mixing the active compound with an inert diluent, such as calcium phosphate, in the presence of disintegrating agents, for example corn starch, and lubricating agents, for example magnesium stearate, and forming tablets. of the mixture by known methods. The tablets can be formulated in a manner known to those skilled in the art, so as to give a sustained release of the compounds of the present invention. These tablets can, if desired, be provided with enteric coatings by known methods, for example by the use of cellulose acetate phthalate. Similarly, capsules, for example hard or soft gelatine capsules, containing the active compound, with or without added excipients, can be prepared by conventional means and, if desired, provided with enteric coatings in a known manner. The tablets and capsules may conveniently contain each of 1 to 500 mg of the active compound. Other compositions for oral administration include, for example, aqueous suspensions containing the active compound in an aqueous medium, in the presence of a non-toxic suspending agent, such as sodium carboxymethylcellulose, and oily suspensions containing a compound of the present invention in suitable vegetable oils, for example peanut oil. The solid oral dosage forms can be formulated in a manner known to those skilled in the art, so as to give a sustained release of the active compound. Form of solid, coated, enteric oral doses comprising the compositions of the present invention may advantageously depend on the nature of the active compound. Various materials, for example, lacquer and / or sugar, may be present as coatings, or otherwise modify the physical form of the oral dosage form. For example, tablets or pills can, if desired, be provided with enteric coatings, by known methods, for example by the use of cellulose acetate phthalate and / or hydroxypropyl methylcellulose phthalate. Capsules and / or mini-capsules (for example hard or soft gelatin capsules), which comprise the active compound (with or without added excipients, such as a fatty oil), can be prepared by conventional means and, if desired, provided with enteric coatings in a known manner. The contents of the capsule and / or mini-capsules can be formulated using known methods to give a sustained release of the active compound. Liquid oral dosage forms, comprising the compositions of the present invention, may be an elixir, suspension and / or syrup (eg, aqueous suspensions containing the active compound in an aqueous medium, in the presence of a suspending agent non-toxic (such as sodium carboxymethylcellulose) and / or oily suspensions containing the active compound in a suitable vegetable oil (such as peanut and / or sunflower oil) The liquid oral dosage forms may also comprise one or more sweetening agents, flavoring agents, preservatives and / or mixtures thereof The active compound can be formulated in granules with or without additional excipients.The granules can be ingested directly by the patient or can be added to a suitable liquid carrier (e.g. The granules may contain disintegrants (for example a pharmaceutically acceptable effervescent couple, formed from a acid and a carbonate and bicarbonate salt) to facilitate dispersion in the liquid medium. Preferably, each of the above oral dosage forms may contain about 1 to 1000 mg, more preferably 5 to 500 mg (eg, 10, 50, 100, 200 or 400 mg) of the active compound. Compositions of the invention suitable for rectal administration are the known dosage forms for such administration, for example, suppositories with hard fat, semi-synthetic glycerides, cocoa butter and / or polyethylene glycol bases. The pharmaceutical compositions may also be administered parenterally (eg, subcutaneously, intramuscularly and / or intravenously (such as by injection and / or infusion) in known pharmaceutical dosage forms for parenteral administration (eg, sterile suspensions in aqueous and / or oily media). and / or sterile solutions in suitable solvents, preferably isotonic with the patient's blood intended.) Parenteral dosage forms can be sterilized (for example by microfiltration and / or using suitable sterilizing agents (such as ethylene oxide)). , one or more of the following pharmaceutically acceptable adjuvants suitable for parenteral administration can be added to the parenteral dosage forms: local anesthetics, preservatives, regulating agents and / or their mixtures Parenteral dosage forms can be stored in sealed containers suitable sterile (for example ampollet ace and / or jars) until use. To increase stability during storage, the parenteral dosage form can be frozen after filling the container and the fluid (eg water) can be removed under reduced pressure. The pharmaceutical compositions can be administered nasally in known pharmaceutical forms for such administration (for example sprays, aerosols, solutions and / or nebulized powders). Dosaged dosage systems, known to those skilled in the art (for example aerosols and / or inhalers) can be used.

The pharmaceutical compositions can be administered by the oral cavity (for example sublingually) in known pharmaceutical forms for such administration (for example slow dissolution tablets, chewing gums, troches, tablets, lozenges, gels, pastes, mouthwashes, rinses and / or powders). Compositions for topical administration comprise a matrix in which the pharmacologically active compounds of the present invention are dispersed so that the compounds are kept in contact with the skin, in order to administer these compounds transdermally. A suitable transdermal composition can be prepared by mixing the pharmaceutically active compound with a topical carrier, such as a mineral oil, petrolatum and / or a wax, for example paraffin wax or beeswax, together with a potential transdermal accelerator, such as dimethyl sulfoxide or propylene glycol. Alternatively, the active compounds can be dispersed in a pharmaceutically acceptable cream or ointment base. The amount of the active compound contained in a topical formulation must be that in which a therapeutically effective amount of the compound is delivered during the period of time for which the topical formulation is attempted to be on the skin.

The compounds of the present invention can also be administered by continuous infusion from an external source, for example by intravenous infusion or from a source of the compound placed within the body. Internal sources include the implanted reservoirs containing the compound to be infused, which is continuously released, for example, by osmosis and implants which may be (a) liquid, such as a suspension or solution, in a pharmaceutically acceptable oil of the compound to be infused, for example in the form of water-soluble derivatives very sparingly, such as a dodecanoate salt or (b) a solid in the form of an implanted support, for example of a synthetic resin or a waxy material , for the compound to be infused. The support can be a simple body containing the entire compound or a series of several bodies, each containing part of the compound to be delivered. The amount of the active compound present in an internal source must be such that a therapeutically effective amount of the compound is delivered over an extended period of time. In some formulations, it may be beneficial to use the compounds of the present invention in the form of very small size particles, for example as obtained by grinding fluid energy.

In the compositions of the present invention, the active compound can, if desired, be associated with other compatible, pharmacologically active ingredients. The present invention also comprises the use of a compound of formula I as a medicament. Pharmaceutical compositions containing a therapeutically effective amount of a compound of formula I can be used to treat depression, anxiety, psychosis (eg, schizophrenia), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, cerebral ischemia, obsessive-compulsive behavior, panic attacks, social phobias, eating disorders and anorexia, diabetes mellitus not dependent on insulin, hyperglycemia or stress in humans. While the precise amount of the active compound administered in such treatment will depend on a number of factors, for example the age of the patient, the severity of the condition and the past medical history and is always within the sound discretion of the physician administering it, the amount of the active compound administered per day is in the range of 1 to 1000 mg, preferably 5 to 500 mg given in a single dose or in divided doses, in one or more times during the day.

A further aspect of the present invention relates to the use of a compound of formula I in the manufacture of a medicament for treating depression, anxiety, psychosis (eg schizophrenia), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, cerebral ischemia, obsessive-compulsive behavior, panic attacks, social phobias, disorders of feeding and anorexia, diabetes mellitus not dependent on insulin, hyperglycemia or stress in humans The present invention also provides a method for treating depression, anxiety, psychosis (eg schizophrenia), tardive dyskinesia, obesity, addition to drugs, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, cerebral ischemia, obsessive-compulsive behavior, panic attacks, social phobias, eating disorders and anorexia, diabetes mellitus not dependent on insulin, hyperglycemia or stress in humans, which comprises the administration of a therapeutically effective amount of a compound of Formula I to a patient who needs it. Processes for the preparation of compounds of formula I will now be described. These processes are preferably carried out at atmospheric pressure.

The compounds of the formula I can be prepared by the dehydration of a compound of the formula II: wherein A, Ri, 2, R3, R4, R5, g and n have the above definitions, in the presence of an acid, for example acetic or sulfuric acid, at a temperature in the range of 0-200 ° C, preferably in the range from 20 to 1502C. The compounds of the formula II can be prepared by the reaction of a compound of the formula III: H S = ((CR2R3) n lll N / H wherein R2, R3 and n have the above definitions, with a compound of formula IV: wherein Z is an leaving group, for example a halogen, such as bromine, and A, Rj_, R4, R5 and g have the above definitions, at a temperature in the range of 0-200BC, in the presence of a solvent, for example ethanol and, optionally, in the presence of an acid, for example, acetic acid; preferably by heating to a temperature in the range of 20 to 150oc. The compounds of the formula I can be prepared directly by the reaction of a compound of the formula III with a compound of the formula IV, at a temperature in the range of 0-200BC, optionally in the presence of an acid, for example the acetic acid and, optionally, in the presence of a solvent, for example ethanol, without isolation of the intermediate of the formula II; preferably heating at a temperature in the range of 20-150oc. The compounds of the formula IV, in which Z is halogen, can be prepared by the reaction of a compound of the formula V: wherein A, Ri, R4, R5 and g have the above definitions, with a halogenating agent, for example a brominating agent, such as phenyltrimethylammonium tribromide or copper (II) bromide, at a temperature in the range of 0-200SC, in the presence of a solvent, for example tetrahydrofuran, preferably at a temperature in the range of 20 to 150 ° C. Compounds of the formula IV, wherein Z is chloro, can also be prepared by the reaction of a compound of the formula VI: wherein A, R, R5 and g have the above definitions, with a compound of the formula R4CH (C1) C0C1, in the presence of a Lewis acid, for example aluminum chloride (III) or tin chloride (IV) ), in a suitable solvent, at a temperature in the range of -20 to 150 ° C.

The compounds of the formula V can be prepared by the reaction of a compound of the formula VII: wherein A, Ri, R5 and g have the above definitions, with a metallating agent, for example butyllithium, followed by an acylating agent, for example a compound of the formula R4CH2CONMe2, in a suitable solvent, for example tetrahydrofuran, at a temperature in the range of -60 to 1500C. The compounds of the formula V can also be prepared by the reaction of a compound of the formula VI with a compound of the formula R 4 CH 2 COCl, in the presence of a Lewis acid, for example aluminum chloride (III) or tin chloride (IV), in a suitable solvent, at a temperature in the range of -20 to 150 ° C. The compounds of the formula V, in which A is O and R5 is H, can be prepared by heating a compound of the formula VIII: wherein i, R4 and g have the above definitions, with the dimethyl acetal of dimethylformamide, at a temperature in the range of 0 to 150 ° C, followed by cooling and reaction with the boron tribromide. Compounds of the formula V in which A is S and 4 and R5 are H, can be prepared by the methods described in KC Majumdar and BS Thyagarajan, International Journal of Sulfur Chemistry, A, 1972, 2, 67 and 93, as outlined below: Compounds of formula V in which A is S , R4 and R5 are H and Ri and g have the above definitions, can be prepared by the reaction of a compound of the formula IX: wherein g is O, 1, 2, 3 or 4, with the concentrated sulfuric acid, at a temperature in the range of 90 to 952c. Compounds of formula IX can be prepared by the reaction of a compound of formula X: wherein Ri and g have the above definitions, with a base, for example sodium hydroxide, in a solvent, for example dichloromethane, at a temperature in the range of 20 to 1500C. Compounds of formula X can be prepared by heating a compound of formula XI: wherein Ri and g have the above definitions, in the presence of a suitable solvent, for example chloroform, at a temperature in the range of 20 to 150SC, preferably in the range of 80 to 90CC. Compounds of the formula XI can be prepared by the reaction of a compound of the formula XII: wherein Ri and g have the above definitions, with an oxidizing agent, for example m-chloroperoxybenzoic acid, in a solvent, for example chloroform, at a temperature in the range of 0 to 40SC. Compounds of the formula XII can be prepared by the reaction of a compound of the formula XIII: XIII XCH2 CH2.OPh wherein X is an leaving group, for example halogen, such as chlorine, with a compound of the formula XIV: wherein i and g have the above definitions, in the presence of a base, for example potassium hydroxide, in a solvent, for example a mixture of ethanol and water, at a temperature in the range of 20 to 150ac. Compounds of formula XIII can be prepared by the reaction of l, 4-dichlorobut-2-yl with the phenol, in the presence of a base, for example potassium hydroxide, in a solvent, for example a mixture of ethanol and water, at a temperature in the range of 20 to 1502C. The ability of the compounds of the formula I to interact with the 5-hydroxytryptamine (5-HT) receptors has been demonstrated by the following test, which determines the ability of the compounds to inhibit ligand binding to the receptors 5-HT in vitro and, in particular, to 5-HT? A receptors. The hippocampal tissue of the brains of Sprague-Dawley rats (Charles River, weight range 150 to 250 g) was homogenized in 50 mM of the ice-cooled Tris-HCl buffer (pH 7.7, when measured at 25 ° C, 1:40 weight / volume) and centrifuged at 30,000g to 4SC for 10 minutes. The re-homogenized pellet in the same regulator, incubated at 37 ° C for 10 minutes and centrifuged at 30,000 G at 4 ° C for 10 minutes. The final pellet was resuspended in 50 mM of the Tris-HCl buffer (pH 7.7). it contains 4 mM of CaCl2, 0.1% of L-ascorbic acid and 10 μM of pargyline hydrochloride (equivalent to 6.25 mg by wet tissue weight / ml) and was used immediately in the ligand assay. Aliquots (400 μl, equivalent to 2.5 mg tissue / tube wet weight) of this membrane preparation were added to tubes containing [3H] 8-hydroxy-2- (dipropylamino) tetralin ([3H] 8- OH-DPAT, 50μl, 2 nM) and distilled water (50 μl, total ligand) or 5-HT (50 μl, 10 μM, non-specific ligand) or the test compound (50 μl, at a single concentration of 10" "6 M or at 10 concentrations ranging from 10-11 to 10 ~ 13 M) and incubated for 30 minutes at 252C. Incubation was terminated by rapid filtration under vacuum through Skatron 11734 filters with the use of a Skatron cell harvester. The filters were washed with 50 mM of the ice-cold Tris-HCl buffer, pH 7.7 (at 252C, wash cycle 9.9.0) and dried. The labeled filter paper discs were placed in flasks, scintillation fluid was added and the radioactivity was determined by counting the liquid scintillation.

The percent displacement of the specific ligand of the tritiated ligand was calculated as a single concentration (10 ~ 6M) of the test compound. The displacement curves were then produced for those compounds that were displaced > 50% of the specific ligand of the ligand tritiated to IO ^ M. using a range of compound concentrations. The concentration giving a 50% inhibition of the specific ligand (IC50) was obtained from the curve. The inhibition coefficient Ki was then calculated using the formula: IC 50 Ki = 1 + ([ligand] / Ko) in which the [ligand] is the concentration of the tritiated ligand used and Ko is the equilibrium dissociation constant for the ligand. The ability of the compounds of the formula I to interact with the reuptake sites of 5-hydroxytryptamine (5-HT) has been demonstrated by the following test that determines the ability of the compounds to inhibit the reuptake of 5-HT in vitro The frontal cortical tissue of the brains of male Sprague-Dawley rats (Charles River; 150-250 g) was homogenized in 0.32 M sucrose cooled with ice (1:10 weight / volume) using a Teflon hub driven by a motor (difference in diameter between the mortar and the 0.5 mm hub). Cell and nucleic debris were removed by centrifugation at 1,500 g and 4dC, for 410 minutes. The pellet (Pl) was discarded and the supernatant centrifuged at 30,000 g and 40 C for 10 minutes. The crude synaptosomal pellet (P2) was resuspended in the Krebs-Henseleit buffer (equivalent to 8.3 mg of tissue wet weight / ml). The crude synaptosomes were incubated in a shaking water bath at 37 ° C for 15 minutes. Aliquots (150 μl, equivalent to 1.25 mg tissue / tube dry weight) were then added to tubes containing 275 μl of the Krebs-Henseleit buffer and 50 μl of the Krebs-Henseleit buffer (total uptake) or 50 μl of the compound of test (at a single concentration of 10 ~ 6 M or at 10 concentrations ranging from 10"11 to 10 ~ 13 M) or 50 μl of zimeldine (10 ~ 5M, non-specific uptake) The uptake was initiated by the addition of 25 μl of freshly prepared [3 H] 5-HT (2nM), followed by vortexing and continued for 5 minutes at 37 ° C in the stirred water bath.The uptake was terminated by filtration under vacuum through Skatron 22734 filters using a Skatron cell harvester The filters were washed with 8 ml of ice-cold saline The marked filter paper discs were placed in flasks, the scintillation fluid was added and the radioactivity was determined by the counting of the liquid scintillation. skill of the compuest The formula I for interacting with the sites of the reuptake of nor-adrenaline has been demonstrated by the following test, which determines the ability of the compounds to inhibit the uptake of noradrenaline in vitro. The frontal cortical tissue of the brain of male Sprague-Dawley rats (Charles River, weight range 150-250 g) was homogenized in ice-cold 0.32M sucrose (1.10 weight / volume) using a Telfon-driven motor hub (difference in diameter between the mortar and the 0.5 mm mace). Nucleic and cellular debris was removed by centrifugation at 1,500 g at 4 ° C for 10 minutes. The pellet (Pl) was discarded and the supernatant centrifuged at 30,000 G at 40C for 10 minutes. The crude synaptosomal pellet (P2) was resuspended in a physiological Krebs regulator (equivalent to 16.7 mg wet weight of tissue / ml). The crude synaptosomes were incubated in a shaking water bath at 37 ° C for 15 minutes. Aliquots (150 μl, equivalent to 1.25 mg of tissue / tube dry weight) were then added to tubes containing 275 μl of the physiological Krebs regulator or 50 μl of test compound (at a single concentration of 10 ~ 6 M or 10 concentrations ranging from 10"11 to 10 ~ 13 M) or 50 μl of desipramine (10 ~ 5M, non-specific uptake). Uptake was initiated by the addition of 25 μl of [3H] ñoradrenaline (10 nM) followed by The vortex was continued for 5 minutes at 37 ° C in the stirred water bath.The uptake was terminated by filtration under vacuum through GF / B filters using a Brandell cell harvester.The filters were washed with 8 ml of saline. The labeled filter paper discs were placed in flasks, the scintillation fluid was added and the radioactivity was determined by counting the liquid scintillation, for both tests of 5-HT uptake and uptake of the ñoradrenaline, the percentage of Inhibition of the specific uptake of the tritiated ligand was calculated for a single concentration (10 ~ 6) of the test compound. The inhibition curves were then produced by the compounds that inhibited a specific uptake of >; 50% of the ligand tritiated at 10 ~ 6 M, using a range of concentrations of the test compound. The concentration of 50% inhibition of specific uptake (IC50) was obtained from the curve. The inhibition constant (Ki) was calculated from the formula: IC 50 Ki = 1 + ([ligand] / Km) in which the [ligand] is the concentration of the tritiated ligand used and Km is the affinity of the uptake site for the ligand The Ki (nM) values obtained in the above tests for the 5-HT? ^ And 5-HT ligand and the NA uptake for each of the final products of Examples 1 to 8 below, are given in Table I The values are the averages of three independent determinations, unless indicated otherwise. The% of the figures are for the% displacement of 10 ~ 6M TABLE 1 * the value is the average of two independent determinations ** the value is the result of a determination NT = not tested These types of activity are indicative of a compound that has utility in the treatment of disorders of the Central Nervous System, particularly depression and anxiety. The compounds of the formula I can have an improved pharmacological profile over the compounds known in the art. The invention is illustrated by the following Examples, which are provided only in exemplary form. The final product of each of these Examples was characterized by one or more of the following procedures: high performance liquid chromatography; elementary analysis; Magnetic-nuclear resonance spectroscopy and infrared spectroscopy.

Example 1 A solution of phenyltrimethylammonium tribromide (9.6 g) in tetrahydrofuran (20 ml) was added in drops in 15 minutes at room temperature to a stirred solution of 3-acetylbenzo [b] thiophene (5 g) in tetrahydrofuran (50 ml). ), then the mixture was stirred at room temperature for 35 minutes. Water (100 ml) was added and the resulting solid was collected by filtration, washed with water (2 x 50 ml) and dried under vacuum at room temperature to give 3- (2-bromoacetyl) benzo [b] thiophene. as a white solid (2.4 g). A mixture of 3- (2-bromoacetyl) benzo [b] thiophene (2.39 g), 2-imidazolidinethione (0.78 g), ethanol (60 ml) and acetic acid (40 ml) was heated under reflux for 18 hours, then allowed to cool to room temperature. The resulting solid was collected by filtration, washed with ether (2 x 50 ml) and dried under vacuum at room temperature to obtain the dihydrate of the 3- (benzo [b] thiophen-3-yl) -5 monobromohydrate, 6-dihydroimidazo [2, 1-b] thiazole, as a white solid (2.96 g), melting point (PF) of 239-240ac. Alternative Preparation The phenyltrimethylammonium tribromide (26.32 g) was added in portions in 45 minutes at -5ac under nitrogen to a stirred solution of 3-acetylbenzo [b] thiophene (12.34 g) in tetrahydrofuran (100 ml), then the mixture was stirred at room temperature for 1 hour. The resulting solid was collected by filtration, washed with ether (100 ml), dried in vacuo at room temperature and crystallized from ethanol to give 3- (2-bromoacetyl) benzo [b] thiophene as a solid of color white (10.8 g). A mixture of 3- (2-bromoacetyl) benzo [b [thiophene (10.0 g), 2-imidazolidinethione (4.0 g), ethanol (120 ml) and acetic acid (80 ml) was heated under reflux for 24 hours, then allowed to cool to room temperature. The resulting solid was collected by filtration and dried in vacuo at room temperature to give the 1,8-hydrate monohydro-hydrate of 3- (benzo [b] thiophen-3-yl) -5,6-dihydroim-idazo [2.1 -b] thiazole as a white solid (11.8 g), MP: 227-229aC.

Example 2 A mixture of 3- (2-bromoacetyl) benzo [b] thiophene (3.35 g, prepared in a manner similar to that described in Example 1, Alternative Preparation), 3,4,5,6-tetrahydro-2- pyrimidinetiol (1.5 g), ethanol (150 ml) and acetic acid (100 ml) was heated under reflux for 18 hours, then the solvents were removed under vacuum to leave an orange hygroscopic solid (4.96 g). A mixture of the orange solid (4.84 g) and 5M sulfuric acid (50 ml) was heated at 90-952C for 18 hours then allowed to cool to room temperature. The resulting solid was collected by filtration, washed with ether (3 x 50 ml) and dried in vacuo at room temperature to give the 0.45 sulfate of 0.1-hydrobromide of 3- (benzo [b] thiophen-3-yl) - 6,7-dihydro-5H-thiazolo [3,2-a] pyrimidine as a pale pink solid (4.92 g). The mixture of salts (3 g) was made basic by the addition of an excess of a 1M aqueous sodium hydroxide solution, and the product was extracted into dichloromethane (3 × 45 ml). The extracts were dried (MgSO 4) and the solvent was removed in vacuo to leave 3- (benzo [b] thiophen-3-yl) -6,7-dihydro-5H-thiazolo [3,2-a] pyrimidine. as a cream-colored solid (1.73 g). P. F. of 155-158ac.

Example 3 A mixture of l- (2-methoxyphenyl) propan-2-one (10 g) and dimethylformamide dimethylacetal (17.8 g) was stirred at 80 ° C under nitrogen for 4 hours, then concentrated in vacuo to leave a viscous oil. The oil was dissolved in dichloromethane (80 ml) and the solution was stirred and cooled in an ice bath, while boron tribromide (1M solution in dichloromethane, 104 ml) was added in drops over 15 minutes. When the addition was complete, the mixture was stirred, with ice cooling, for an additional 1.5 hours, then emptied into an excess of ice and a saturated aqueous solution of sodium hydrogen carbonate. The product was extracted with dichloromethane (3x 200 ml) and the combined extracts were washed with water (2 x 200 ml), dried (Na 2 SO 4) and the solvent was removed in vacuo to leave 3-acetyl-benzo [b. ] furan as a dark red oil (4.25 g). A solution of phenyltrimethylammonium tribromide (2.47 g) in tetrahydrofuran (20 ml) was added dropwise, at room temperature, under nitrogen over 5 minutes to a stirred solution of 3-acetylbenzo [b] furan (1 g) in tetrahydrofuran (20 ml), then the The mixture was stirred at room temperature for 1.5 hours more, filtered and the solvent was removed in vacuo. The residue was triturated with ether and the resulting solid was collected by filtration and dried under vacuum at room temperature, to give 3- (2-bromo-acetyl) benzo [b] furan as an almost white solid (0.25 g) . A mixture of 3- (2-bromoacetyl) benzo [b] furan (0.25 h), 2-imidazolidinthione (0.11 g), ethanol (30 ml) and acetic acid (20 ml) was heated under reflux for 20 hours, then allowed to cool to room temperature. The resulting solid was collected by filtration, washed with ether and dried in vacuo at room temperature to give the monohydrate of the 3-benzo [b] furan-3-yl) -5,6-dihydroimidazo monobromide [2]. lb] thiazole as a white solid (0.145 g), PF: 242.2440C. Alternative Preparation A mixture of l- (2-methoxyphenyl) propan-2-one (77.2 g) and the dimethylformamide dimethylformamide (137.5 g) was stirred at 80 ° C under nitrogen for 4 hours, then concentrated in vacuo to leave a viscous oil. The oil was dissolved in dichloromethane (620 ml), then the stirred solution was cooled to oac. Boron tribromide (1M dichloromethane solution, 800 ml) was added in drops over 1.75 hours at 0-5dC, then the mixture was stirred at 0-5ac for 1.5 hours more and emptied into an excess of ice and a aqueous and saturated solution of sodium hydrogen carbonate. The solid sodium hydrogencarbonate was added in portions, with occasional stirring until the effervescence ceased. The product was extracted into dichloromethane (3 x 600 ml) then the combined extracts were washed with water (2 x 600 ml), dried (Na 2 SO 4) and the solvent was removed in vacuo to leave 3-acetylbenzofb] - furan as a brown oil (78.9 g). A stirred suspension of copper (II) bromide, freshly ground (87.4 g) in ethyl acetate (625 ml), was heated to reflux temperature under nitrogen, then a solution of 3-acetylbenzo [b] furan ( 40 g) in chloroform (625 ml). The mixture was then heated under reflux, with vigorous stirring, for 5 hours, allowed to stand at room temperature for 48 hours, heated again to reflux for 1 hour, cooled to room temperature and filtered. The solvents were removed in vacuo, the residue was triturated with ether (1 liter) and the resulting solid was collected by filtration, ground to a fine powder and dried under vacuum at room temperature to give 3- (2-bromoacetyl). ) benzo [b] furan as a dark gray solid (26 g). The concentration of the ethereal liquor provided a second crop of the gray solid (10.9 g). A mixture of 3- (2-bromoacetyl) benzo [b] furan (36.9 g), 2-imidazolidinethione (15.75 g), ethanol (600 ml) and acetic acid (400 ml) was heated under reflux for 21 hours, then allowed to cool to room temperature. The resulting solid was collected by filtration, washed with ether (500 ml) and dissolved in hot methane (500 ml). Charcoal (2 g) was added and the hot mixture was stirred for a few minutes, then filtered and allowed to cool to room temperature. The resulting solid was cured by filtration, ground to a fine powder and dried under vacuum at 80 ° C, to give monohydrohydrate hydrate 0.7 of 3- (benzo [b] furan-3-yl) -5,6-dihydroimidazo [ 2, lb] thiazole, as an almost white solid (28.1 g). P.F .: 251-254-5ac.

Example 4 A stirred suspension of copper (II) bromide (3.95 g) in chloroform mixture (25 ml) and ethyl acetate (25 ml) was heated to reflux temperature and the 3-acetylbenzo [b] furan (1.7 g, prepared as described in Example 3, Alternative Preparation). The stirred mixture was heated under reflux for 1 hour, cooled to room temperature, filtered and the solvents removed in vacuo. The residue was dissolved in a mixture of ethanol (30 ml) and acetic acid (20 ml), 3,4,5,6-tetrahydro-2-pyrimidinetiol (0.25 g) was added and the mixture was heated to reflux for 18 hours. hours. The solvents were removed in vacuo, 1M sulfuric acid (20 ml) was added, then the mixture was heated to 90-95ßc for 48 hours, cooled to room temperature and made basic by the addition of an aqueous solution of hydroxide. sodium 1M. The product was extracted into chloroform (3 x 20 ml), then the combined extracts were dried (Na 2 SO 4) and the solvent was removed under vacuum to give 3- (benzo [b] furan-3-yl) -6, 7-dihydro-5H-thiazolo [3,2-a] pyridine as a pale yellow solid (0.15 g), PF :: 128-130BC.

Example 5 A mixture of phenol (50.8 g), potassium hydroxide (30 g), ethanol (200 ml) and water (50 ml) was stirred under reflux for 1 hour, then cooled to 30 ° C. A solution of 1,4-dichlorobut-2-nO (100 g) in ethanol (60 ml) was added dropwise over 3.5 hours, then the mixture was stirred at room temperature for 18 hours and filtered. The filter mass was washed with ethanol (60 ml) and the filtrate and washings were combined. The solvents were removed in vacuo and the residue was distilled to give l-chloro-4-phenoxybut-2-yne as a colorless oil (52.5 g (boiling point (PE) from 92.982C to 0.53 mbar). Potassium hydroxide (16.3 g) in a mixture of ethanol (480 ml) and water (120 ml) was added at room temperature, under nitrogen, to a stirred solution of 4-chlorothiophenol (42 g) in a mixture of ethanol (425 ml) and water (25 ml), then the mixture was stirred at room temperature for 4 hours.A solution of l-chloro-4-phenoxybut-2-yne (52.5 g) in a mixture of ethanol (425 ml. ) and water (25 ml) was added in drops over 3 hours, then the mixture was stirred at room temperature for 18 hours, and filtered.The mass of the filter was washed with water (500 ml), then the combined filtrate and the washings were concentrated in vacuo to remove the ethanol The product was extracted from the aqueous residue using ethyl acetate (2 x 250 ml), and the combined extracts were washed with water (100 ml) and saturated brine (50 ml), dried (MgSO 4) and the solvent was removed under vacuum to leave a mixture of 4: 1 del- (4-chlorophenylthio) -4-phenoxybut-2-yne and the l-chloro-4-phenoxybut-2-yne, as a pale yellow oil (79.65 g), which was used without purification. A solution of m-chloroperoxybenzoic acid (55% purity, 81 g) in dichloromethane (1400 ml) was added in drops over 2.5 hours to a stirred, ice-cooled solution of 1- (4-chlorophenylthio) -4-phenoxybutyl -2-N crude (74.5 g) in dichloromethane (600 ml), then the mixture was stirred at room temperature for 18 hours and filtered. The filtrate was washed with an aqueous solution of 5% sodium carbonate (3 x 750 ml) and water (3 x 500 ml), then dried (Na 2 S 4) and the solvent was removed in vacuo. The residue was dissolved in hot dichloromethane (40 ml), then petroleum ether (PE: 60-80ac) (75 ml) was added and the mixture was triturated to give a sticky solid, which was collected by filtration, triturated with warm ether (500 ml), was collected by filtration and dried in vacuo to give l- (4-chloro-phenylsulfinyl) -4-phenoxybut-2-yne, as a solid (21.73 g), PF: 102-103SC . A mixture of 1- (4-chlorophenylsulfinyl) -4-phenoxy-but-2-yne (17.45 g) and chloroform (150 ml) was heated under nitrogen at an external temperature of 80-85ac, for 5 hours, and the solvent it was removed under vacuum to leave 5-chloro-3-methylene-2-phenoxymethyl-2, 3-dihydrobenzo [b] thiophen-2-ol, as a viscous, greenish-yellow oil (17.45 g). A solution of 5-chloro-3-methylene-2-phenoxymethyl-2,3-dihydrobenzo [b] thiophen-2-ol (16.9 g) in dichloromethane (250 ml) was shaken vigorously for a few seconds with an aqueous solution of 5M sodium hydroxide (150 ml), then the organic solution was separated, washed with water (150 ml), dried (MgSO 4) and the solvent was removed under vacuum to leave the l- (5-chloro-2 , 3-dihydrobenzo [b] thiophen-3-yl) -2-phenoxyethanone as a pink solid (16.4 g), which was used without further purification. A mixture of l- (5-chloro-2,3-dihydro-benzo [b] thiophen-3-yl) -2-phenoxyethanone (15.3 g), acetic acid (75 ml) and concentrated sulfuric acid (15 drops) it was heated to 90-952C under nitrogen for 20 hours, then the solvent was removed in vacuo. The residue was partitioned between dichloromethane (250 ml) and a 5M aqueous sodium hydroxide solution (100 ml), then the aqueous phase was separated and washed with dichloromethane (50 ml). The combined dichloromethane solutions were washed with water (100 ml), dried (MgSO4) and the solvent removed in vacuo to leave 3-acetyl-5-chlorobenzo [b] thiophene as a reddish-brown oil (10.7 g. ), which solidified slowly at room temperature. The phenyltrimethylammonium tribromide (3.6 g) was added in portions under nitrogen over 30 minutes to a stirred suspension of 3-acetyl-5-chlorobenzo [b] thiophene (2 g) in tetrahydrofuran (25 ml), then the mixture was stirred at the room temperature for 3 hours and filtered. The filter mass was washed with tetrahydrofuran (10 ml), then the filtrate and the washings were combined and the solvent was removed under vacuum to leave the 3- (2-bromoacetyl) -5-chloro-benzo [b] thiophene as a solid gray (4.2 g), which was used without purification. A mixture of the crude 3- (2-bromoacetyl) -5-chlorobenzo- [b] thiophene (4.2 g), 2-imidazolidinthione (1 g), ethanol (25 ml) and acetic acid (10 ml) was heated to low reflux nitrogen, for 18 hours, then allowed to cool to room temperature. The resulting solid was collected by filtration, washed with ethanol (15 ml) and dried in vacuo to give the monobromhydrate of 3- (5-chlorobenzo [b] thiophen-3-yl) -5,6-dihydroimidazo [2, lb] thiazole, as a white solid (2.1 g), MP: 286-288ac (decomposition).

Example 6 A solution of potassium hydroxide (14.9 g) in a mixture of ethanol (450 ml) and water (110 ml) was added at room temperature under nitrogen to a stirred solution of 4-methoxythiophenol (32.7 g) in a mixture. of ethanol (400 ml) and water (25 ml), then the mixture was stirred at room temperature for 4 hours. A solution of l-chloro-4-phenoxybut-2-ino (48 g, prepared in a manner similar to that described in Example 5) in a mixture of ethanol (400 ml) and water (25 ml) was added, in drops, about 3 hours, then the mixture was stirred at room temperature for 18 hours. The mixture was concentrated in vacuo to remove the ethanol, then the product was extracted into ethyl acetate (2 x 250 ml). The combined extracts were washed with water (100 ml) and saturated brine (50 ml), dried (MgSO 4) and the solvent removed in vacuo to leave a mixture of l: 1- (4-methoxy-phenylthio) ) -4-phenoxybut-2-yne and l, 4-bis- (4-methoxy-phenylthio) but-2-yne, as an oil /76.9 g) which was used without further purification. A solution of m-chloroperoxybenzoic acid (55% pure, 84.9 g) in dichloromethane (1400 ml) was added, in drops, over 2.5 hours, to a stirred, ice-cooled solution of l- (4-methoxyphenylthio) - Crude 4-phenoxybut-2-yne (76.9 g) in dichloromethane (600 ml), then the mixture was stirred at room temperature for 18 hours and filtered. The filtrate was washed with an aqueous solution of 5% sodium carbonate (3x750 ml) and water (3x500 ml), then dried (Na2S4) and divided into two equal portions. The solvent was removed from the first portion by distillation at atmospheric pressure, to leave the crude l- (4-methoxyphenylsulfinyl) -4-phenoxybut-2-yne as a dark brown gum (44 g). The solvent was removed under vacuum from the second portion, to leave the crude 1- (4-methoxyphenylsulfinyl) -4-phenoxybut-2-yne, as an orange-yellow gum (31.4 g). The analysis of nuclear magnetic resonance (NMR) of both gums indicated that the second being of greater purity, so it was used in the subsequent stages. A mixture of crude 1- (4-methoxyphenylsulfinyl) -4-phenoxybut-2-yne (2.1 g) and chloroform (25 ml) was heated under nitrogen at an external temperature of 80-85ac for 1 hour, allowed to stand room temperature for 18 hours and was encouraged at an external temperature of 90-95ac for 6 hours. The solvent was removed by distillation to leave crude 5-methoxy-3-methylene-2-phenoxymethyl-2,3-dihydrobenzo [b] thiophen-2-ol as an orange gum. This gum was dissolved in dichloromethane (30 ml) and the solution was shaken vigorously for a few seconds with a 5M aqueous sodium hydroxide solution (25 ml), then the organic solution was separated, washed with water (25 ml), dried (MgSO 4) and the solvent was removed in vacuo to leave crude l- (5-methoxy-2,3-dihydrobenzo [b] thiophen-3-yl) -2-phenoxyethanone as a red gum ( 1.94 g), which was used without purification. A mixture of crude l- (5-methoxy-2,3-dihydro-benzo [b] thiophen-3-yl) -2-phenoxyethanone (1.94 g), acetic acid (10 ml) and concentrated sulfuric acid (2 drops) ) was heated at 90-95ac for 18 hours, then the solvent was removed in vacuo. The residue was partitioned between dichloromethane (50 ml) and 5M aqueous sodium hydroxide solution (30 ml), then the aqueous phase was separated and washed with dichloromethane (30 ml). The combined dichloromethane solutions were washed with water (20 ml), dried (MgSO 4) and the solvent removed in vacuo to leave a tan gum (1.3 g). This gum was purified by evaporative chromatography on silica, using 10-15% mixtures of ethyl acetate and petroleum ether (P.E .: 60-80ac) as diluents. The appropriate fractions were combined, and the solvents were removed in vacuo to leave 3-acetyl-5-methoxybenzo [b] thiophene as a pale brown gum (0.37 g). Phenyltrimethylammonium tribromide (0.66 g) was added in portions, under nitrogen, about 30 minutes, to a stirred solution of 3-acetyl-5-methoxybenzo [b] thiophene (0.36 g) in tetrahydrofuran (5 ml), then the mixture was stirred at room temperature for 1.75 hours and filtered. The filter mass was washed with tetrahydrofuran (5 ml), then the filtrate and the washings were combined and the solvent was removed in vacuo. The residue was dissolved in ethanol (8 ml), acetic acid (2 ml) and the 2-imidazolidinethione (0.18 g) was added and the mixture was refluxed under nitrogen for 18 hours, then allowed to cool to room temperature. The resulting solid was collected by filtration, washed with ethanol (5 ml) and dried in vacuo at 70 ° C to give the mono-hydrobromide of 3- (5-methoxybenzo [b] thiophen-3-yl) -5,6- dihydro-imidazo [2, 1-b] thiazole, as a beige solid (0.3 g), PF: 246-2482C.

Alternative Preparation A solution of potassium hydroxide (3.4 g) in a mixture of ethanol (110 ml) and water (28 ml) was added dropwise at room temperature, under nitrogen, to a stirred solution of 4-methoxythiophenol (8.55 g). ) in a mixture of ethanol (100 ml) and water (6.5 ml), then the mixture was stirred at room temperature for 3.5 hours. A solution of 1-chloro-4-phenoxybut-2-yne (11 g, prepared in a manner similar to that described in Example 5) in a mixture of ethanol (100 ml) and water (6.5 ml) was added dropwise. about 1.5 hours, then the mixture was stirred at room temperature for 18 hours. This mixture was concentrated in vacuo to remove the ethanol, then the product was extracted into ethyl acetate (2 x 80 ml). The combined extracts were washed with water (30 ml) and saturated brine (20 ml), dried (MgSO 4) and the solvent removed in vacuo to leave an oil (17.7 g). This oil was purified by evaporative chromatography on silica, using 10-20% mixtures of ethyl acetate and petroleum ether (P .: 60.802C) as diluents. The appropriate fractions were combined and the solvents were removed in vacuo to leave l- (4-methoxyphenylthio) -4-phenoxybut-2-yne, as an oil (13.7 g). A solution of m-chloroperoxybenzoic acid (55% purity: 15.2 g) in chloroform (300 ml) was added in drops, over 2.5 hours, to a stirred, ice-cooled solution of 1- (4-methoxyphenylthio) -4 -fenoxibut-2-ino (13.7 g) in chloroform (125 ml), then the mixture was stirred at room temperature for 18 hours and filtered. The filtrate was washed with a solution of 5% sodium carbonate (3x150 ml) and water (3x100 ml), then dried (MgSO 4) and filtered. The filtrate was heated under nitrogen at an external temperature of 80-85 ° C for 6 hours, allowed to stand at room temperature for 18 hours, heated to an external temperature of 80-85 ° C for a further 1.5 hours, then allowed to cool. The solvent was removed in vacuo, the residue dissolved in dichloromethane (250 ml) and the solution shaken vigorously for a few seconds with a 5M aqueous sodium hydroxide solution (150 ml). The organic solution was separated, washed with water (2 x 150 ml), dried (MgSO 4) and the solvent removed in vacuo. The residue was purified by evaporative chromatography on silica, using mixtures of 12.5-25% ethyl acetate and petroleum ether (P .: 60-80ac) as diluents. The appropriate fractions were combined and the solvents were removed in vacuo to leave l- (5-methoxy-2,3-dihydrobenzo [b] thiophen-3-yl) -2-phenoxy-ethanone as a gum (4.5 g). A mixture of l- (5-methoxy-2,3-dihydro-benzofb] thiophen-3-yl) -2-phenoxyethanone (4.5 g), acetic acid (20 ml) and concentrated sulfuric acid (5 drops) was heated under nitrogen at 90-952C for 3 hours, then the solvent was removed in vacuo. The residue was partitioned between dichloromethane (100 ml) and a 5M aqueous sodium hydroxide solution (50 ml), then the aqueous phase was separated and washed with dichloromethane (50 ml). The combined dichloromethane solutions were washed cor. water (50 ml), dried (MgSO 4) and the solvent was removed under vacuum to leave an orange-brown oil (3.2 g). This oil was purified by evaporative chromatography on silica, using mixtures of 20-25% ethyl acetate and petroleum ether (P.E .: 6O-80ac) as diluents. The appropriate fractions were combined and the solvents were removed in vacuo to leave 3-acetyl-5-methoxybenzo [b] thiophene as an almost white solid (1.8 g). The phenyltrimethylammonium tribromide (3.3 g) was added in portions, under nitrogen, over 30 minutes to a stirred solution of 3-acetyl-5-methoxybenzo [b] thiophene (1.8 g) in tetrahydrofuran (20 ml), then the mixture was stirred. stirred at room temperature for 1 hour and filtered. The filter mass was washed with tetrahydrofuran (20 ml), then the filtrate and the washings were combined and the solvent was removed in vacuo. The residue was dissolved in ethanol (25 ml), acetic acid (18 ml) and the 2-imidazolidinethione (0.9 g) was added and the mixture was refluxed under nitrogen for 18 hours, then allowed to cool to room temperature. The resulting solid was collected by filtration, washed with ethanol (25 ml) and dried under vacuum at 70 ° C to give the monobromhydrate of 3- (5-methoxybenzo [b] thiophen-3-yl) -5,6-dihydroimidazo [ 2, 1-b] thiazole as a white solid (1.55 g). P.F .: 246-2482C.

Example 7 A solution of potassium hydroxide (11.5 g) in a mixture of ethanol (340 ml) and water (85 ml) was added at room temperature, under nitrogen, to a stirred solution of 4-fluorothiophenol (26.3 g) in a mixture of ethanol (300 ml)) and water (18 ml), then the mixture was stirred at room temperature for 4 hours. A solution of l-chloro-4-phenoxybut-2-yne (37 g, prepared in a manner similar to that described in Example 5) in a mixture of ethanol (300 ml) and water (18 ml) was added, in drops, about 1.5 hours, then the mixture was stirred at room temperature for 24 hours. The mixture was concentrated in vacuo to remove the ethanol, then the product was diluted with water (100 ml) and extracted into ethyl acetate (2 x 250 ml). The combined extracts were washed with water (100 ml) and saturated brine (100 ml), dried (MgSO 4), and the solvent was removed in vacuo to leave a yellow oil (59.2 g). This oil partially solidified at room temperature and the solid was collected by filtration, washed with petroleum ether (PE: 40.602C) and dried under vacuum at room temperature to give l- (4-fluorophenylthio) - 4-phenoxybut-2-yne as a white solid (39.2 g). A solution of m-chloroperoxybenzoic acid (purity 55%; 23.1 g) in chloroform (450 ml) was added, in drops, over 2.75 hours to a stirred, ice-cooled solution of l- (4-fluorophenylthio) -4-phenoxybut-2-yne ( 20 g) in chloroform (190 ml), then the mixture was stirred at room temperature for 18 hours and filtered. The filtrate was washed with an aqueous solution of 5% sodium carbonate (3 x 230 ml) and water (3 x 150 ml), then dried (MgSO 4) and refiltered. The filtrate was heated under nitrogen at an external temperature of 80-85ac for 1.5 hours, allowed to stand at room temperature for 18 hours, heated to an external temperature of 80-85ac for 7 hours and allowed to stand at room temperature for 65 hours. The solvent was removed in vacuo to leave 5-fluoro-3-methylene-2-phenoxymethyl-2,3-dihydrobenzo [b] thiophen-2-ol as a yellow viscous oil (22.45 g). This oil was dissolved in dichloromethane (380 ml) and the solution was shaken vigorously for a few seconds with a 5M aqueous solution of sodium hydroxide (230 ml), then the organic solution was separated, washed with water (4 x 230 ml). ) and dried (MgS? 4). The solvent was removed in vacuo to leave the crude 1- (5-fluoro-2,3-dihydrobenzo [b] thiophen-3-yl) -2-phenoxyethanone as a pink oil (20.6 g), which solidified slowly at room temperature. A mixture of crude l- (5-fluoro-2,3-dihydro-benzo [b] thiophen-3-yl) -2-phenoxyethanone (23 ml) and concentrated sulfuric acid (6 drops) was heated to 90-95 ° C. under nitrogen for 16 hours, then the solvent was removed in vacuo. The residue was partitioned between dichloromethane (120 ml) and a 5M aqueous sodium hydroxide solution (60 ml), then the aqueous phase was separated and washed with dichloromethane (60 ml). The combined dichloromethane solutions were washed with water (4x50 ml), dried (MgSO 4), and the solvent was removed in vacuo to leave a reddish-brown solid (3.55 g). The solid was purified by evaporative chromatography on silica, using a 17: 3 mixture of petroleum ether (P .: 60.80ac) and ethyl acetate as diluents. The appropriate fractions were combined and the solvents were removed in vacuo to leave 3-acetyl-5-fluorobenzo [b] thiophene as an almost white solid (1.8 g), P.F .: 90-922C. The phenyltrimethylammonium tribromide (0.4 g) was added, in portions, under nitrogen, over 30 minutes, to a stirred solution of 3-acetyl-5-fluorobenzo [b] thiophene (0.2 g) in tetrahydrofuran (4.5 ml), then the The mixture was stirred at room temperature for 1 hour, allowed to stand at this room temperature for 18 hours and filtered. The solvent was removed in vacuo and the residue was combined with the product derived in a similar manner from 3-acetyl-5-fluorobenzo [b] thiophene (1.5 g). The combined residues were dissolved in ethanol (47 ml), 2-imidazolidin-thione (0.9 g) and acetic acid (31 ml) were added, and the mixture was heated to reflux under nitrogen for 20 hours, then allowed to cool to room temperature. The resulting precipitate was collected by filtration, washed with ethanol and dried under vacuum at 60 ° C to give the 3- (5-fluoro-benzo [b] thiophen-3-yl) -5,6-dihydroimidazo [2, lb] thiazole as a yellow crystalline solid (1.7 g), PF: 264-266ac.

Example 8 A solution of potassium hydroxide (7.5 g) in a mixture of ethanol (220 ml) and water (55 ml) was added at room temperature under nitrogen to a stirred solution of 4-mercaptobenzonitrile (18.0 g, prepared in accordance with the method of S. Krishnamurthy and D. Aimino, J. Org. Chem., 1989, 54/4458) in a mixture of ethanol (195 ml) and water (12 ml), then the mixture was stirred at room temperature for 4.5 hours. A solution of l-chloro-4-phenoxybut-2-yne (24.2 g, prepared in a manner similar to that described in Example 5) in a mixture of ethanol (195 ml) and water (12 ml) was added dropwise about 1.5 hours, then the mixture was stirred at room temperature for 17 hours. This mixture was concentrated in vacuo to remove the ethanol, then the product was diluted with water (150 ml) and extracted into ethyl acetate (2 x 250 ml). The combined extracts were washed with water (100 ml) and saturated brine (100 ml), dried (MgSO 4) and the solvent removed under vacuum to leave 4- (4-phenoxybut-2-inylthio) benzonitrile as a solid almost white (37.7 g). A solution of m-chloroperoxybenzoic acid (55% purity, 23.1 g) in chloroform (450 ml) was added in drops, over 2.5 hours, to a stirred, ice-cooled solution of 4- (4-phenoxybut-2-inylthio) ) benzonitrile (22.1 g) in chloroform (190 ml), then the mixture was stirred at room temperature for 16 hours and filtered. The filtrate was washed with a 5% aqueous solution of sodium carbonate (3 x 230 ml) and water (3 x 150 ml), then dried (MgSO 4) and refiltered. The filtrate was heated under nitrogen at an external temperature of 80-85ac for 1.5 hours, allowed to stand at room temperature for 18 hours, heated to an external temperature of 80-852C for 6 hours and allowed to stand at room temperature for 18 hours. The solvent was removed under vacuum to leave the crude 2-hydroxy-3-methylene-2-phenoxymethyl-2,3-dihydrobenzo [b] thiophene-5-carbo-nitrile as an almost white solid (22.7 g). The solid was dissolved in dichloromethane (380 ml) and the solution was shaken vigorously for a few seconds with a 5M aqueous solution of sodium hydroxide (230 ml), then the organic solution was separated, washed with water (4 x 230 ml). ) and dried (MgS? 4). The solvent was removed in vacuo to leave the crude 3- (2-phenoxyacetyl) -2,3-dihydro-benzo [b] thiophene-5-carbonitro as a pale pink solid (23.1 g). A mixture of crude 3- (2-phenoxyacetyl) -2,3-dihydro-benzo [b] thiophene-5-carbonitro (5 g), acetic acid (20 ml) and concentrated sulfuric acid (5 drops) was heated to 90 -95 g under nitrogen, for 20 hours, then the solvent was removed in vacuo. The residue was partitioned between dichloromethane (100 ml) and a 5M aqueous solution of sodium hydroxide (60 ml), then the aqueous phase was separated and washed with dichloromethane (50 ml). The combined dichloromethane solutions were washed with water (6 x 50 ml), dried (MgSO 4), and the solvent was removed in vacuo to leave a pink solid (3.5 mg). The solid was purified by evaporative chromatography on silica, using a 3: 2 mixture of petroleum ether (P .: 60-80ac) and ethyl acetate as diluent. The appropriate fractions were combined, and the solvents were removed in vacuo to leave 3-acetylbenzo [b [thiophene-5-carbonitrile as a pale pink solid (1.5 g). A solution of phenyltrimethylammonium tribromide (2.8 g) in tetrahydrofuran (5 ml) was added, in drops, under nitrogen, over 30 minutes, to a stirred solution of 3-acetylbenzo [b] thiophene-5-carbonitrile (1.5 g) in tetrahydrofuran (50 ml), then the mixture was stirred at room temperature for 2 hours. The resulting solid was collected by filtration and triturated with a hot mixture of ethanol (21 ml) and acetic acid (14 ml). The product was collected by filtration and dried under vacuum to give 3- (bromoacetyl) benzo [b] thiophene-5-carbonitrile as a white solid (1.05 g). A mixture of 3- (bromoacetyl) benzo [b] thiophene-5-carbonitrile (1.05 g), 2-imidazolidin-thione (0.4 g) ethanol (31.5 ml) and acetic acid (21 ml), was heated to reflux under nitrogen for 24 hours and cooled with ice. The resulting precipitate was collected by filtration, washed with ether and dried in vacuo at 65 ° C to give the monohydro-hydrate of 3- (5,6-dihydroimidazo [2, lb] thiazol-3-yl) benzo [b [thiophene-5 -carbonitrile as a white solid (1 g). P.F .: 303-305ac Example 9 The use of the compounds of the present invention in the manufacture of pharmaceutical compositions is illustrated. In this description, the term "active compound" denotes any compound of the invention, but particularly any compound that is the final product of one of the preceding examples. a) Capsules In the preparation of the capsules, 10 parts by weight of the active compound and 240 parts by weight of lactose were disaggregated and mixed. The mixture was filled into hard gelatin capsules, each capsule containing a unit dose or a unit dose part of the active compound. b) Tablets Tablets of the following ingredients were prepared: Parts by weight Active compound 10 Lactose 190 Corn starch 22 Polyvinylpyrrolidone 10 Magnesium stearate 3 The active compound, lactose and some of the starch were disaggregated, mixed and the resulting mixture was granulated with a solution of polyvinylpyrrolidone in ethanol. The dried granulate was mixed with magnesium stearate and the rest of the starch. The mixture was then compressed in a tablet machine, to give tablets each containing a unit dose or part thereof of the active compound. c) Enteric coated tablets Tablets were prepared by the above method (b).

The tablets were enteric coated in a conventional manner, using a solution of 20% cellulose acetate phthalate and 3% diethyl phthalate in ethanol: dichloromethane (1: 1). d) Suppositories In the preparation of suppositories, 100 parts by weight of the active compound were incorporated into 1300 parts by weight of the triglyceride suppository base and the mixture was formed into suppositories each with a therapeutically effective amount of the active ingredient.

Claims

CLAIMS 1. Compounds of formula I: which include their pharmaceutically acceptable salts, wherein: A is S (0) p or O; p is 0, 1 and 2; g is O, 1, 2, 3, 6, 4; n is 2 or 3; Ri is a) halogen, b) an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, c) an alkoxy group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, d) an alkylthio group, an alkylsulfinyl group or an alkylsulfonyl group, each having 1 to 3 carbon atoms, optionally substituted by one or more halogens, e) hydroxy, f) an acyloxy group containing 1 to 3 carbon atoms, g) a hydroxyalkyl group containing 1 to 3 carbon atoms, h) cyano, i) an alkanoyl group containing 1 to 6 carbon atoms, j) an alkoxycarbonyl group containing 2 to 6 carbon atoms, k) a group carbamoyl or a sarbamoylmethyl group, each optionally N-substituted by one or two alkyl groups, which contain 1 to 3 carbon atoms, 1) a sulfamoyl or sulfamoylmethyl group, each optionally N-substituted by one or two alkyl groups, each with 1 to 3 carbon atoms or m) an amino group, optionally substituted by one or two alkyl groups, each having 1 to 3 carbon atoms; Ri, which are the same or different, when g is 2, 3 or 4; R2-R3 and R4 'independently, are H or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens; and R5 is a) halogen, b) an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, c) an alkoxy group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens , d) is an alkylthio group, an alkylsulfinyl group or an alkylsulfonyl group, each having 1 to 3 carbon atoms, optionally substituted by one or more halogens, e) hydroxy, f) an acyloxy group containing 1 to 3 carbon atoms, carbon, g) a hydroxyalkyl group having 1 to 3 carbon atoms, h) cyano, i) an alkanoyl group containing 1 to 6 carbon atoms, j) an alkoxycarbonyl group containing 2 to 6 carbon atoms, k) a carbamoyl group or a carbamoylmethyl group, each, optionally, N-substituted by one or two alkyl groups, each having 1 to 3 carbon atoms, 1) a sulfamoyl or sulfamoylmethyl group, each, optionally, N-substituted by one or two alkyl groups, each with 1 to 3 carbon atoms, m) an amino group, optionally substituted by one or two alkyl groups, each having 1 to 3 carbon atoms or n) is H.
2. Compounds of formula 1, as claimed in claim 1, wherein A is S (0) p or O; p is 0, l 6 2; g is 0, 1, 2, 3 or 4; n is 3; Ri is a) halogen, b) an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, c) an alkoxy group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, d) an alkylthio group, an alkylsulfinyl group or an alkylsulfonyl group, each having 1 to 3 carbon atoms, optionally substituted by one or more halogens, e) hydroxy, f) an acyloxy group containing 1 to 3 carbon atoms, g) a hydroxyalkyl group containing 3 carbon atoms, h) cyano, i) an alkanoyl group containing 1 to 6 carbon atoms, j) an alkoxycarbonyl group containing 2 to 6 carbon atoms, k) a carbamoyl group or a carbamoylmethyl group, each, optionally, N-substituted by one or two alkyl groups, each having 1 to 3 carbon atoms, 1) a sulfamoyl or sulfamoylmethyl group, each optionally N-substituted by one or two alkyl groups , each with 1 to 3 carbon atoms om) an amino group, optionally substituted by one or two alkyl groups, each having 1 to 3 carbon atoms; Ri are the same or different groups when g is 2, 3 or 4; R2, R3 and R4 are, independently, H or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens; and R3 is H, halogen or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens.
3. Compounds of formula I, as claimed in claim 1, wherein A is S (0) p; p is o, l or 2; g is 0, 1, 2, 3 or 4; n is 2, Ri is a) halogen, b) an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, c) an alkoxy group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, d) an alkylthio group, an alkylsulfinyl group or an alkylsulfonyl group, each having 1 to 3 carbon atoms, optionally substituted by one or more halogens, e) hydroxy, f) an acyloxy group containing 1 to 3 carbon atoms, g) a hydroxyalkyl group containing 1 to 3 carbon atoms, h) cyano, i) an alkanoyl group containing 1 to 6 carbon atoms, j) an alkoxycarbonyl group containing 2 to 6 carbon atoms, k) a carbamoyl group or a carbamoylmethyl group, each, optionally, N-substituted by one or two alkyl groups, each having 1 to 3 carbon atoms, 1) a sulfamoyl or sulfamoylmethyl group, each, optionally, N- substituted by one or two alkyl groups, each with 1 to 3 carbon atoms bond or m) an amino group, optionally substituted by one or two alkyl groups, each having 1 to 3 carbon atoms; Ri are the same or different groups when g is 2, 3 or 4; R2, R3 and R4, independently, are H or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens; and R5 is H, halogen or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens.
4. Compounds of the formula I, as claimed in claims 1 to 3, wherein p is 0; g is 0 or 1; R is halogen, an alkoxy group containing 1 to 3 carbon atoms, or cyano; 2, R3, R4 and R5 are all H; and n is 2.
5. Compounds of formula I, as recited in claim 1, wherein A is O; g is 0, 1, 2, 3 or 4; n is 2; Ri is a) halogen, b) an alkyl group containing from 1 to 3 carbon atoms, optionally substituted by one or more halogens, c) an alkoxy group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens , d) an alkylthio group, an alkylsulfinyl group or an alkylsulfonyl group, each having 1 to 3 carbon atoms, optionally, substituted by one or more halogens, e) hydroxy, f) an acyloxy group, with 1 to 3 carbon atoms, carbon, g) a hydroxyalkyl group containing 1 to 3 carbon atoms, h) cyano, i) an alkanoyl group containing 1 to 6 carbon atoms, j) an alkoxycarbonyl group containing 2 to 6 carbon atoms, k) a carbamoyl group or a carbamoylmethyl group, each, optionally, N-substituted by one or two alkyl groups, with 1 to 3 carbon atoms, 1) a sulfamoyl or sulfamoylmethyl group, each, optionally, N-substituted by no or two alkyl groups, each with 1 to 3 carbon atoms om) a group am ino, optionally substituted by one or two alkyl groups, each with 1 to 3 carbon atoms; Ri are the same or different groups when g is 2, 3 or 4; R2, R3 and R4, independently, are H or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens; and R5 is H, halogen or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens.
6. Compounds of the formula I, as claimed in claims 1 or 5, wherein n is 2, g is 0 or 1; Ri is halogen, an alkoxy group containing 1 to 3 carbon atoms or cyano; R2, R3, R4 and R5 are all H; and n is 2.
7. Compounds of the formula I, as claimed in claim 1, selected from the group consisting of: 3- (benzo [b] thiophen-3-yl) -5,6-dihydroimidazo [2, 1-b] thiazole; 3- (benzo [b] thiophen-3-yl) -6,7-dihydro-5H-thiazolo [3,2-a] -pyrimidine; 3- (benzo [b] furan-3-yl) -5,6-dihydroimidazo [2, 1-b] thiazole; 3- (benzo [b] furan-3-yl) -6,7-dihydro-5H-thiazolo [3,2- a] -pyrimidine; 3- (5-chlorobenzo [b [thiophen-3-yl] -5,6-dihydroimidazo [2, 1-b] -thiazole; 3- (5-methoxybenzo [b] thiophen-3-yl) -5,6-dihydroimidazo [2, 1-b] thiazole; 3- (5-fluorobenzo [b] thiophen-3-yl) -5,6-dihydroimidazo [2, lb] -thiazole 3- (5,6-dihydroimidazo [2, lb] thiazol-3-yl) benzo [b ] thiophen-5-carbonitrile; and their pharmaceutically acceptable salts.
8. The compound of formula I, as claimed in claim 1, which is: 3- (benzo [b] thiophen-3-yl) -5,6-dihydroimidazo [2, 1-b] thiazole; and its pharmaceutically acceptable salts.
9. A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula I, as claimed in any of the preceding claims, together with a pharmaceutically acceptable diluent or carrier.
10. Compounds of the formula I, as claimed in claim 1, for use as a medicament.
11. Compounds of formula I, as claimed in claim 1, for use in the treatment of depression, anxiety, psychosis, tardive dyskinesia, obesity, addiction to drugs, drug abuse, cognitive disorders, Alzheimer's disease, dementia senile, cerebral ischemia, obsessive-compulsive behavior, panic attacks, social phobias, eating disorders and anorexia, diabetes mellitus not dependent on insulin, hyperglycemia, or stress, in humans.
12. Use of the compounds of formula I, as defined in claim 1, in the manufacture of a medicament for the treatment of depression, anxiety, psychosis, tardive dyskinesia, obesity, addiction to drugs, drug abuse, cognitive disorders , Alzheimer's disease, senile dementia, cerebral ischemia, obsessive-compulsive behavior, panic attacks, social phobias, eating disorders and anorexia, diabetes mellitus not dependent on insulin, hyperglycemia, or stress, in humans.
13. A method to treat depression, anxiety, psychosis, tardive dyskinesia, obesity, addiction to drugs, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, cerebral ischemia, obsessive-compulsive behavior, panic attacks, social phobias, Eating disorders and anorexia, non-insulin-dependent diabetes mellitus, hyperglycemia, or stress, in humans, this method comprises administering a therapeutically effective amount of a compound of formula I, as claimed in claim 1, to a patient who needs treatment.
14. Process for the preparation of compounds of the formula I, as claimed in claim 1, comprising the reaction of a compound of the formula III: with a compound of formula IV: at a temperature in the range of 0 to 200ac, optionally in the presence of an acid and optionally in the presence of a solvent.