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Title:
DIHYDROIMIDAZO[2,1-B]THIAZOLE AND DIHYDRO-5H-THIAZOLO[3,2-A]PYRIMIDINE DERIVATIVES WITH 5-HT RECEPTOR AFFINITY
Document Type and Number:
WIPO Patent Application WO/2002/026747
Kind Code:
A1
Abstract:
The present invention relates to certain novel substituted dihydroimidazo[2,1-b]thiazole and dihydro-5H-thiazolo[3,2-a]pyrimidine compounds of Formula (I) which have affinity for 5-HT¿1A? receptors and which inhibit neuronal reuptake of 5-hydroxytryptamine and/or noradrenaline, to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, obsessive-compulsive behaviour, panic attacks, social phobias, eating disorders such as bulimia, anorexia, snacking and binge eating, non-insulin dependent diabetes mellitus, hyperglycaemia, hyperlipidaemia, stress, as an aid to smoking cessation and in the treatment and/or prophylaxis of seizures, neurological disorders such as epilepsy and/or conditions in which there is neurological damage such as stroke, brain trauma, cerebral ischaemia, head injuries and haemorrhage.

Inventors:
Brough, Paul (R5 Pennyfoot Street Nottingham NG1 1GF, GB)
Watts, John Paul (R5 Pennyfoot Street Nottingham NG1 1GF, GB)
Cockroft, Victor (R5 Pennyfoot Street Nottingham NG1 1GF, GB)
Kerrigan, Frank (R5 Pennyfoot Street Nottingham NG1 1GF, GB)
Doyle, Kevin James (R5 Pennyfoot Street Nottingham NG1 1GF, GB)
Application Number:
PCT/GB2001/004317
Publication Date:
April 04, 2002
Filing Date:
September 27, 2001
Export Citation:
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Assignee:
KNOLL GMBH (Knollstrasse Ludwigshafen, 67061, DE)
Brough, Paul (R5 Pennyfoot Street Nottingham NG1 1GF, GB)
Watts, John Paul (R5 Pennyfoot Street Nottingham NG1 1GF, GB)
Cockroft, Victor (R5 Pennyfoot Street Nottingham NG1 1GF, GB)
Kerrigan, Frank (R5 Pennyfoot Street Nottingham NG1 1GF, GB)
Doyle, Kevin James (R5 Pennyfoot Street Nottingham NG1 1GF, GB)
International Classes:
A61P25/24; C07D513/04; (IPC1-7): C07D513/04; A61K31/425; A61P25/24
Domestic Patent References:
WO1997002269A1
WO2000071548A1
WO2000071549A1
WO2001068653A1
Other References:
SHARPE C J ET AL: "PHENACYLTHIOIMIDAZOLINES AND 3-ARYL-5,6-DIHYDROIMIDAZO[2,1-BÜTHIAZOLES WITH ANTIDEPRESSANT ACTIVITY" JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 14, no. 10, 1971, pages 977-982, XP002015395 ISSN: 0022-2623 cited in the application
Attorney, Agent or Firm:
Nash, David Allan (Haseltine Lake & Co. Imperial House 15-19 Kingsway London WC2B 6UD, GB)
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Claims:
Claims
1. Compounds of Formula I including pharmaceutical acceptable salts thereof in which g is 0, 1, 2, 3, 4 or 5 ; n is 2 or 3; R, is a) halo, b) an alkyl group containing 1 to 3 carbon atoms optionally substituted by one or more halo, c) an alkoxy group containing 1 to 3 carbon atoms optionally substituted by one or more halo, d) an alkylthio group, an alkylsulphinyl group or an alkylsulphonyl group each containing 1 to 3 carbon atoms optionally substituted by one or more halo, e) hydroxy, X an acyloxy group containing 1 to 3 carbon atoms, g) a hydroxyalkyl group containing 1 to 3 carbon atoms, h) cyano, i) an alkanol 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 Nsubstituted by one or two alkyl groups each containing 1 to 3 carbon atoms, I) a sulphamoyl or sulphamoylmethyl group each optionally Nsubstituted by one or two alkyl groups each containing 1. to 3 carbon atorris, or m) an amino group optionally substituted by one or two alkyl groups each containing 1 to 3 carbon atoms; Ri being the same or different when g is 2,3,4 or 5; R2 represents H, an alkyl group containing 1 to 6 carbon atoms optionally substituted by one or more halo, a hydroxyalkyl group containing 1 to 6 carbon atoms, an a hydroxyarylmethyl group, a hydroxyalkenyl group containing 3 to 6 carbon atoms in < which hydroxy is not attached directly to either carbon of the double bond, a hydroxyalkynyl group containing 3 to 6 carbon atoms in which hydroxy is not attached directly to either carbon of the triple bond, a hydroxycycloalkyl group containing 3 to 6 carbon atoms, an alkenyl group containing 2 to 8 carbon atoms, an arylalkenyl group containing 8 to 10 carbon atoms, a cycloalkyl group containing 3 to 6 carbon atoms, a C3cycioalkoxyC13alkyl group, a C37 alkynylalkoxyC13alkyl group, a C47 cycloalkylalkoxyC13alkyl group, a C13alkoxyC13alkyl group, a C13alkylthioC13alkyl group, a C13alkoxy group, a C13alkylthio group, an arylthio group, a C16 alkanoyl group, a C3. 6 alkoxycarbonylalkyl group, cyano, halo, a C1 4alkyliminomethyl group, a C14alkylaminoalkyl group or a hydroxyiminomethyl group ; and wherein the condensed thiazole ring is attached at the 4,5,6 or 7position of the benzofuran ring.
2. Compounds of Formula I according to claim 1 in which g is 0, 1 or 2; n is 2 or 3 ; Ri is halo, an alkyl group containing 1 to 3 carbon atoms, an alkoxy group containing 1 to 3 carbon atoms or hydroxy; and R2 represents H, an alkyl group containing 1 to 3 carbon atoms, an alkenyl group containing 2 to 3 carbon atoms, a hydroxyalkyl group containing 1 to 6 carbon atoms, or a C13alkylthio group.
3. Compounds according to either claim 1 or claim 2 in which n is 2.
4. Compounds of Formula) according to claim 1 as represented by Formula) Il in which R1, R2, n and g are as initially defined.
5. Compounds of Formula 1 according to claim 1 as represented by Formula ill in which R1, R2, n and g are as initially defined.
6. Compounds of Formula I according to claim 1 as represented by Formula IV in which RI, R2, n and g are as initially defined.
7. Compounds of Formula # according to claim 1 as represented by Formula V in which Ri, R2, n and g are as initially defined.
8. Compounds according to any one of claims 4 to 7 in which g is 0,1 or 2; n is 2 or 3; R, is halo, an alkyl group containing 1 to 3 carbon atoms, an alkoxy group containing 1 to 3 carbon atoms. or hydroxy; and Rz represents H, an alkyl group containing 1 to 3 carbon atoms, an alkenyl group containing 2 to 3 carbon atoms, a hydroxyalkyl group containing 1 to 6 carbon atoms, or a C alkylthio group.
9. Compounds according to claim 8 in which n is 2.
10. Compounds according to claim 4 in which g is 0 or 1, n is 2; and R2 represents H, an alkyl group containing 1 to 3 carbon atoms, an alkenyl group containing 2 to 3 carbon atoms, a hydroxyalkyl group containing 1 to 6 carbon atoms, or a C1 3alkylthio group.
11. Compounds according to claim 5 in which g is 0 or 1, n is 2; and R2 represents an alkyl group containing 1 to 3 carbon atoms, an alkenyl group containing 2 to 3 carbon atoms, a hydroxyalkyl group containing 1 to 6 carbon atoms, or a C1<alkylthio group.
12. Compounds according to claim 6 in which g is 0 or 1, n is 2, and R2 represents H, an alkyl group containing 1 to 3 carbon atoms, an alkenyl group containing 2 to 3 carbon atoms, a hydroxyalkyl group containing 1 to 6 carbon atoms, or a C13alkylthio group.
13. Compounds according to claim 7 in which g is 0 or 1, n is 2, and R2 represents H, an alkyl group containing 1 to 3 carbon atoms, an alkenyl group containing 2 to 3 carbon atoms, a hydroxyalkyl group containing 1 to 6 carbon atoms, or a C13alkylthio group:.
14. Compounds. according to any one of claims 10 to 13 in which R2 represents an alkyl group containing 1 to 3 carbon atoms.
15. A compound of Formula I which is 3 (benzojb] furan7yl)2methyl5, 6 dihydroimidazo [2, 1b] thiazoie or a pharmaceutically acceptable salt thereof, including individual enantiomers, racemates or other mixtures of enantiomers.
16. A compound of Formula I which is 3 (benzo [b] furan4yi)2methyl5, 6 dihydroimidazo {2, 1bithiazole or a pharmaceutically acceptable salt thereof, including individual enantiomers, racemates or other mixtures of enantiomers.
17. A pharmaceutical composition comprising a therapeutical effective amount of a compound of Formula I, as claimed in any previous claim, together with a pharmaceutical acceptable diluent or carrier.
18. A compound of Formula I, as claimed in any of claims 1 to 16, for use as a medicament.
19. A compound of Formula 1, as claimed in any of claims 1 to 16, for use in the treatment of depression, anxiety, psychoses, schizophrenia, tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, cerebral ischaemia, obsessivecompulsive behaviour, panic attacks, social phobias, eating disorders such as bulimia, anorexia, snacking and binge eating, noninsulin dependent diabetes mellitus, hyperglycaemia, hyperlipidaemia, and stress, and as an aid to smoking cessation.
20. Use of a compound of Formula I, as claimed in any of claims 1 to 16, in the manufacture of a medicament for use in the treatment of depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, cerebral ischaemia, obsessivecompulsive behaviour, panic attacks, social phobias, eating disorders such as bulimia, anorexia, snacking and binge eating, noninsulin dependent diabetes mellitus, hyperglycaemia, hyperlipidaemia, and stress, and as an aid to smoking cessation.
21. A method of treating depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, cerebral ischaemia, obsessivecompulsive behaviour, panic attacks, social phobias, eating disorders such as bulimia, anorexia, snacking and binge eating, noninsulin dependent diabetes mellitus, hyperglycaemia, hyperlipidaemia, and stress, comprising the administration of a therapeutically effective amount of a compound'of Formula 1, as claimed in any of claims 1 to 16, to a patient in need thereof.
22. A method of reducing the craving to smoke in human beings which comprises the administration of a therapeutical effective amount of a compound of Formula i, as claimed in any of claims 1 to 16, to a patient in need thereof.
23. A method of reducing weight gain after smoking cessation in human beings which comprises the administration of a therapeutically effective amount of a compound of Formula I, as claimed in any of claims 1 to 16, to a patient in need thereof.
24. A compound of Formula !, as claimed in any of claims 1 to 16, for use in the treatment of depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, obsessivecompulsive behaviour, panic attacks, social phobias, eating disorders such as bulimia, anorexia, snacking and binge eating, noninsulin dependent diabetes mellitus, hyperglycaemia, hyperlipidaemia, stress, as an aid to smoking cessation and in the treatment and/or prophylaxis of seizures, neurological disorders such as epilepsy and/or conditions in which there is neurological damage such as stroke, brain trauma, cerebral ischaemia, head injuries and haemorrhage.
25. A compound of Formula I, as claimed in any of claims 1 to 16, for use in the treatment or prevention of metabolic diseases and conditions arising therefrom, in particular non exercise activity thermogenesis and increased metabolic rate, sexual dysfunction, sleep apnoea, premenstrual syndrome, urinary incontinence, hyperactivity disorders, hiatial hernia and reflux esophagitis, pain, especially neuropathic pain, weight gain associated with drug treatment, chronic fatigue syndrome, osteoarthritis and gout, cancers associated with weight gain, menstrual dysfunction, gallstones, orthostatic hypotension and pulmonary hypertension.
26. A compound of Formula 1, as claimed in any of claims 1 to 16, for use in the prevention of cardiovascular disease, in reducing platelet adhesiveness, in aiding weight loss after pregnancy or in aiding weight loss after smoking cessation.
27. A compound of Formula ! as claimed in any one of claims 1 to 16 for use in the treatment obesity and related comorbid conditions.
28. Processes for the preparation of compounds of Formula 1, as described herein.
Description:
Therapeutic Agents The present invention relates to certain novel substituted dihydroimidazo [2, 1- b] thiazole and dihydro-5H-thiazolo [3, 2-a] pyrimidine compounds. which have affinity for 5-HT1A receptors and which inhibit neuronal reuptake of 5-hydroxytryptamine and/or noradrenaline, to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, obsessive- compulsive behaviour, panic attacks, social phobias, eating disorders such as bulimia, anorexia, snacking and binge eating, non-insulin dependent diabetes mellitus, hyperglycaemia, hyperlipidaemia, stress, as an aid to smoking cessation and in the treatment and/or prophylaxis of seizures, neurological disorders such as epilepsy and/or conditions in which there is neurological damage such as stroke, brain trauma, cerebral ischaemia, head injuries and haemorrhage.

WO 98/41528 discloses that compounds of formula A including pharmaceutical acceptable salts thereof in the form of individual enantiomers, racemates, or other mixtures of enantiomers, inwhich: Ar is phenyl, naphthyl or benzo [b] thiophenyl, each of which may be optionally substituted by one or more substituents selected from a) halo, b) an alkyl group containing 1 to 3 carbon atoms optionally substituted by one or more halo, c) an alkoxy group containing 1 to 3 carbon atoms optionally substituted by one or more halo, d) an alkylthio group containing 1 to 3 carbon atoms optionally substituted by one or more halo, e) a phenoxy group optionally substituted by one or more halo or f) phenyl optionally substituted by one or more halo ;

Ri and R2, which may be the same or different, independently are a) H, b) an alkyl group containing 1 to 6 carbon atoms, c) an alkenyl group containing 3 to 6 carbon atoms, d) a cycloalkyl group containing 3 to 7 carbon atoms, e) a cycloalkyimethyl group in which the ring contains 3 to 7 carbon atoms, 0 an aryl orheteroaryl group optionally substituted by one or more substituents-selected fromi) halo, ii) an alkyl group containing 1 to 3 carbon atoms optionally substituted by one or more haio, iii) an alkoxy group containing 1 to 3 carbon atoms optionally substituted by one or more halo, iv) an alkylthio group containing 1 to 3 carbon atoms optionally substituted by one or more halo, g) an arylalkyl or heteroarylalkyl group in which the alkyl chain contains 1 to 3 carbon atoms and in which the aryl or heteroaryl group may optionally be substituted by one or more substituents selected from i) halo, ii) an alkyl group containing 1 to 3 carbon atoms optionally substituted by one or more halo, iii) an alkoxy group containing 1 to 3 carbon atoms optionally substituted by one or more halo, iv) an alkylthio group containing 1 to 3 carbon atoms optionally substituted by one or more halo ; or Ri and R2 form an alkylen chain optionally substituted by one or more alkyl groups each containing 1 to 3 carbon atoms, such that, together with the atoms to which they are attached, they form a 5 or 6 membered ring, R3 is a) H, b) an aryl or heteroaryl group optionally substituted by one or more substituents selected from i) halo, ii) an alkyl group containing 1 to 3 carbon atoms optionally substituted by one or more haio, iii) an alkoxy group containing 1 to 3 carbon atoms optionally substituted by one or more halo, iv) an alkylthio group containing 1 to 3 carbon atoms optionally substituted by one or more halo, c) an arylmethyl group in which the aryl is optionally substituted by one or more substituents selected from i) halo, ii) an alkyl group containing 1 to 3 carbon atoms optionally substituted by one or more halo, iii) an alkoxy group containing 1 to 3 carbon atoms optionally substituted by one or more halo, iv) an alkylthio group containing 1 to 3 carbon atoms optionally substituted by one or more halo ; or d) an alkoxyalkyl group containing 3 to 6 carbon atoms; and R4 and R5, which may be the same or different, independently are an alkyl group containing 1 to 3 carbon atoms, or R4 and R5 together with the atom to which they are attached form a cycloalkyl ring containing 3 to 6 carbon atoms; are useful in the treatment of depression, anxiety, Parkinson's disease, obesity, cognitive disorders, seizures, neurological disorders such as epilepsy, and as

neuroprotective agents to protect against conditions such as stroke. The compounds of the present invention are not disclosed or suggested in this document.

Sharpe C. J and Shadbolt R. S. (Journal of Medicinal Chemistry, 1971, Vol 14 No. 10, p977-982) disclose certain dihydroimidazo [2,1-b] thiazole compounds having antidepressant activity. However, the document also states that these compounds were generally less active and more toxic than the imidazolines also disclosed in the document. The compounds of the present invention are not disclosed or suggested in this document.

WO 97/02269 discloses that compounds of formula B including pharmaceutical acceptable salts thereof in which A is S (O) p or O ; p is 0, 1 or 2 ; g is 0, 1,2,3, or 4 ; n is 2 or 3 ; Ri is a) halo, b) an alkyl group containing 1 to 3 carbon atoms optionally substituted by one or more halo, c) an alkoxy group containing 1 to 3 carbon atoms optionally substituted by one or more halo, d) an alkylthio group, an alkylsulphinyl group or an alkylsulphonyl group each containing 1 to 3 carbon atoms optionally substituted by one or more halo, 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 alkanol 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 containing 1 to 3 carbon atoms, I) a sulphamoyl or sulphamoylmethyl group each optionally N-substituted by one or two alkyl groups each containing 1 to 3 carbon atoms, or m) an amino group optionally

substituted by one or two alkyl groups each containing 1 to 3 carbon atoms; R1 being 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 halo ; and R5 is a) halo, b) an alkyl group containing 1 to 3 carbon atoms optionally substituted by one or more halo, c) an alkoxy group containing 1 to 3 carbon atoms optionally substituted by one or more halo, d) an alkylthio group, an alkylsulphinyl group or an alkylsulphonyl group each containing 1 to 3 carbon atoms optionally substituted by one or more halo, 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 alkanol 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 containing 1 to 3 carbon atoms, 1) a sulphamoyl or sulphamoylmethyl group each optionally N-substituted by one or two alkyl groups each containing 1 to 3 carbon atoms, m) an amino group optionally substituted by one or two alkyl groups each containing 1 to 3 carbon atoms, or n) H ; have affinity for 5-HT1A receptors and inhibit neuronal reuptake of 5-hydroxytryptamine and/or noradrenaline. These compounds are stated to be useful in the treatment of CNS disorders. The compounds of the present invention are not disclosed or suggested in this document.

The prior art compounds generally exhibit activity as monoamine oxidase inhibitors and/or have affinity for other receptors, for example muscarinic receptors, and are therefore likely to cause undesired side effects. Surprisingly, the present invention provides compounds with unexpectedly superior selectivity and efficacy.

International applications nos PCT/EPOO/4279 and PCT/EP00/04280, both filed 11 May 2000, disclose certain substituted dihydroimidazo [2, 1-b] thiazole and dihydro- 5H-thiazoio [3, 2-a] pyrimidine compounds which have affinity for 5-HT1A receptors and inhibit neuronal reuptake of 5-hydroxytryptamine and/or noradrenaline.

US 4,160,768 discloses that 3- (2-benzo [b] furanyl)-5, 6-dihydroimidazo [2,1- thiazole is useful as an anti-inflammatory agent. This document does not disclose or suggest the compounds of the present invention.

The present invention provides compounds of Formula 1

including pharmaceutical acceptable salts thereof in which gisO, 1,2,3,4 or 5; n is. 2 or 3; Ri is a) halo, b) an alkyl group containing 1 to 3 carbon atoms optionally substituted by one or more halo, c) an alkoxy group containing 1 to 3 carbon atoms optionally substituted by one or more halo, d) an alkylthio group, an alkylsulphinyl group or an alkylsulphonyl group each containing 1 to 3 carbon atoms optionally substituted by one or more halo, e) hydroxy, an acyloxy group containing 1 to 3 carbon atoms, g) a hydroxyalkyl group containing 1 to 3 carbon atoms, h) cyano, i) an alkanol 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 containing 1 to 3 carbon atoms, I) a sulphamoyl or sulphamoylmethyl group each optionally N-substituted by one or two alkyl groups each containing 1 to 3 carbon atoms, or m) an amino group optionally substituted by one or two alkyl groups each containing 1 to 3 carbon atoms; Ri being the same or different when g is 2,3,4 or 5; R2 represents H, an alkyl group containing 1 to 6 carbon atoms optionally substituted by one or more halo, a hydroxyalkyl group containing 1 to 6 carbon atoms, an a- hydroxyarylmethyl group, a hydroxyalkenyl group containing 3 to 6 carbon atoms in which hydroxy is not attached directly to either carbon of the double bond, a hydroxyalkynyl group containing 3 to 6 carbon atoms in which hydroxy is not

attached directly to either carbon of the triple bond, a hydroxycycloalkyl group containing 3 to 6 carbon atoms, an alkenyl group containing 2 to 8 carbon atoms, an arylalkenyl group containing 8 to 10 carbon atoms, a cycloalkyl group containing 3 to 6 carbon atoms, a C3-6cycloalkoxyC1-3alkyl group, a C3-7 alkynylalkoxyC1-3alkyl group, a C4-7 cycloalkylalkoxyC1-3alkyl group, a C1-3alkoxyC1-3alkyl group, a C1-3alkylthioC1-3alkyl group, a C1-alkoxy group, a C1-3alkylthio group, an arylthio group, a C1-6 alkanol group, a C3-6 alkoxycarbonylalkyl group, cyano, halo, a C1- 4alkyliminomethyl group, a C1-4 alkylaminoalkyl group or a hydroxyiminomethyl group; and wherein the condensed thiazole ring is attached at the 4,5,6 or 7-position of the benzofuran.

It will be understood that the term halo, when used herein, includes fluoro, chloro, bromo and iodo. It will be understood that in alkyl groups, alkenyl groups, alkynyl groups, alkylthio groups and alkoxy groups containing more than two carbon atoms the alkyl group may be straight or branched. Aryl means phenyl optionally substituted by one or more of the following : halo, a Cl-3 alkyl group or a Cl-3 alkoxy group.

Preferred values of R1 are methyl, ethyl, propyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, bromo, chloro, fluoro, iodo, trifluoromethyl, trifluoromethoxy, methlthio, methylsulphinyl, methylsulphonyl, hydroxy, formyloxy, acetoxy, hydroxymethyl, 1-hydroxyethyl, 1-hydroxy-1-methylethyl, 1-hydroxypropyl, cyano, formyl, acetyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, carbamoylmethyl, sulphamoyl, sulphamoylmethyl, amino, methylamino, dimethylamino, ethylamin or diethylamino. More preferably Ri is methyl, methoxy, chloro, fluoro or hydroxy.

Preferred values of R2 are H, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, methoxy, ethoxy, bromo, chloro, fluoro, iodo, trifluoromethyl, trifluoromethoxy hydroxymethyl, 1-hydroxyethyl, 1-hydroxy-1-methylethyl ; 1-hydroxypropyl, 1- hydroxy-2-methylpropyl, 1-hydroxybutyl, 1-hydroxy-3-methylbutyl, 1-hydroxypentyl, <BR> <BR> <BR> 1-hydroxypropenyl, 1-hydroxybut-3-enyl, 1-hydroxy-2-methylpropenyl, 1-hydroxy-2-<BR> <BR> <BR> <BR> <BR> <BR> <BR> methylbut-3-enyf, 1-hydroxypent4-enyl, 3-hydroxybut-1-enyl, 1-hydroxypropynyl, 1-

hydroxybut-2-ynyl,. a-hydroxy-2-methoxybenzyl, methoxymethyl, ethoxymethyl, isopropoxymethyl, cyclopropylmethoxymethyl, cyclobutylmethoxymethyl, prop-2- ynyloxymethyl, methylthio, phenylthio, vinyl, allyl, prop-1-enyl, 2-methylprop-2-enyl, 1-methylvinyl, styryl, formyl, acetyl, cyano, ethoxycarbonylmethyl, N-(1- methylethyl) iminomethyl, N-methylaminomethyl and hydroxyiminomethyl. More preferably R2 is H, hydroxymethyl, methyl, ethyl, isopropyl, vinyl and methylthio.

Most preferably R2 is hydroxymethyl, methyl or ethyl.

In a first preferred group of compounds of Formula 1 : g is 0, 1 or 2 ; n is 2 or 3 ; Ri is halo, an alkyl group containing 1 to 3 carbon atoms, an alkoxy group containing 1 to 3 carbon atoms or hydroxy; and R2 represents H, an alkyl group containing 1 to 3 carbon atoms, an alkenyl group containing 2 to 3 carbon atoms, a hydroxyalkyl group containing 1 to 6 carbon atoms, or a C1-3alkylthio group.

More preferably g is 0 or 1, for example 0. More preferably n is 2.

A second preferred group of compounds of Formula ! is represented by Formula li in which Ri, R2, n and g are as initially defined.

A third preferred group of compounds of Formula 1 is represented by Formula III

in which Ri, R2, n and g are as initially defined.

A fourth preferred group of compounds of Formula I is represented by FormulaIV in which R1, R2, n and g are as initially defined.

A fifth preferred group of compounds of Formula I is represented by Formula V

in which R1, R2, n and g are as initially defined.

Preferably in compounds of Formulae II, I11, IV and V, g is 0,1 or 2 ; n is 2 or 3 ; Ri is halo, an alkyl group containing 1 to 3 carbon atoms, an alkoxy group containing 1 to 3 carbon atoms or hydroxy; and R2 represents H, an alkyl group containing 1 to 3 carbon atoms, an alkenyl group containing 2 to 3 carbon atoms, a hydroxyalkyl group containing 1 to 6 carbon atoms, or a d-aatkytthio group. More preferably n is 2.

More preferably in compounds of Formula II, g is 0 or 1, n is 2 ; and R2 represents H, an alkyl group containing 1 to 3 carbon atoms, an alkenyl group containing 2 to 3 carbon atoms, a hydroxyalkyl group containing 1 to 6 carbon atoms, or a CI-3alkylthio group. Most preferably R2 is methyl, ethyl, isopropyl, vinyl, hydroxymethyl or methylthio.

More preferably in compounds of Formula III, g is 0 or 1, n is 2; and R2 represents an alkyl group containing 1 to 3 carbon atoms, an alkenyl group containing 2 to 3 carbon atoms, a hydroxyalkyl group containing 1 to 6 carbon atoms, or a C1-3alkylthio group. Most preferably R2 is methyl, ethyl, isopropyl, vinyl, hydroxymethyl or methylthio.

More preferably in compounds of Formula ! V, g is 0 or 1, n is 2, and R2 represents H, an alkyl group containing 1 to 3 carbon atoms, an alkenyl group containing 2 to 3 carbon atoms, a hydroxyalkyl group containing 1 to 6 carbon atoms, or a C1-3alkylthio group. Most preferably R2 is methyl, ethyl, isopropyl, vinyl, hydroxymethyl or methylthio.

More preferably in compounds of Formula V, g is 0 or 1, n is 2, and R2 represents H, an alkyl group containing 1 to 3 carbon atoms, an alkenyl group containing 2 to 3 carbon atoms, a hydroxyalkyl group containing 1 to 6 carbon atoms, or a Calkylthio group. Most preferably R2 is methyl, ethyl, isopropyl, vinyl, hydroxymethyl or methyithio.

Compounds of Formula I may exist as salts with pharmaceutical acceptable acids. The present invention includes all such salts. Examples of such salts include hydrochlorides, hydrobromides, sulphates, methanesulphonates, nitrates, maleates, acetates, citrates, fumarates, tartrates [eg (+)-tartrates, (-)-tartrates or mixtures thereof including racemic mixtures], succinates, benzoates and salts with amino acids such as glutamic acid.

Certain compounds of Formula I may exist in differenttautomeric forms or as different geometric isomers, and the present invention includes eachtautomer and/or geometric isomer of compounds of Formula I and mixtures thereof.

Certain compounds of Formula I may exist in different stable conformational forms which may be separable. For example, if R2 is a bulky group there may be restricted rotation about one or more single bond or bonds due tosteric hindrance.

Torsional asymmetry due to restricted rotation about an asymmetric single bond, for example because of steric hindrance or ring strain, may permit separation of different conformers. The present invention includes each conformational isomer of compounds of Formuia I and mixtures thereof.

Certain compounds of Formula I and their salts may exist in more than one crystal form and the present invention includes each crystal form and mixtures thereof. Certain compounds of Formula I and their salts may also exist in the form of solvates, for example hydrates, and the present invention includes each solvate and mixtures thereof.

Certain compounds of Formula I contain one or morechiral centres, and exist in different optically active forms. When compounds of Formula I contain onechiral centre, the compounds exist in two enantiomeric forms and the present invention includes both enantiomers and mixtures of enantiomers. The enantiomers may be resolved by methods known to those skilled in the art, for example by formation of

diastereoisomeric salts which may be separated, for example, by crystallisation ; formation of diastereoisomeric derivatives or complexes which may be separated, for example, by crystallisation, 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 where the desired enantiomer is converted into another chemical entity by one of the separation procedures described above, a further step is required to liberate the desired enantiomeric form. Alternatively, specific enantiomers may be synthesised by asymmetric synthesis using optically active reagents, substrates, catalysts or solvents, or by converting one enantiomer into the other by asymmetric transformation.

When a compound of Formula I contains more than one chiral centre it may exist in diastereoisomeric forms. The diastereoisomeric pairs may be separated by methods known to those skilled in the art, for example chromatography or crystallisation and the individual enantiomers within each pair may be separated as described above. The present invention includes each diastereoisomer of compounds of Formula I and mixtures thereof.

A preferred group of compounds of Formula I are compounds, including pharmaceutical acceptable salts thereof, in which g is 0,1 or 2, preferably 0 or 1 nis2 R, is a) halo, b) an alkyl group containing 1 to 3 carbon atoms optionally substituted by one or more halo, c) an alkoxy group containing 1 to 3 carbon atoms optionally substituted by one or more halo, d) an alkylthio group, an alkylsulphinyl group or an alkylsulphonyl group each containing 1 to 3 carbon atoms optionally substituted by one or more halo, e) hydroxy, X an acyloxy group containing 1 to 3 carbon atoms, g) a hydroxyalkyl group containing 1 to 3 carbon atoms, h) cyano, i) an alkanol 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 M-substituted by one or two alkyl groups each containing 1 to 3 carbon atoms, I) a suiphamoyl or sulphamoylmethyl group each optionally N-substituted by one or two

alkyl groups each containing 1. to 3 carbon atoms, or m) an amino group optionally substituted by one or two alkyl groups each containing 1 to 3 carbon atoms; R1 being the same or different when g is 2; R2 represents H or an alkyl group containing 1 to 6 carbon atoms, an alkyl group containing 1 to 6 carbon atoms optionally substituted by one or more halo, a hydroxyalkyl group containing 1 to 6 carbon atoms, an a-hydroxyarylmethyl group, a hydroxyalkenyl group containing 3 to 6 carbon atoms in which hydroxy is not attached directly to either carbon of the double bond, a hydroxyalkynyl group containing 3 to 6 carbon atoms in which hydroxy is not attached directly to either carbon of the triple bond, a hydroxycycloalkyl group containing 3 to 6 carbon atoms, an alkenyl group containing 2 to 8 carbon atoms, anarylalkenyl group containing 8 to 10 carbon atoms, a cycloalkyl group containing 3 to 6 carbon atoms, a C3- 6cycloalkoxyC1-3alkyl group, a C3-7 alkynylalkoxyC1-3alkyl group, a C4- 7cycloalkylalkoxyC1-3alkyl group, a C1-3alkoxyC1-3alkyl group, a C1-3alkylthioC1-3alkyl group, a C1-3alkoxy group, a C1-3alkylthio group, an arylthio group, a C1-6 alkanoyl group, a C3-6 alkoxycarbonylalkyl group, cyano, halo, a C, 4alkyliminomethyl group, a C1-4alkylaminoalkyl group or a hydroxyiminomethyl group; and wherein the condensed thiazole ring may be attached at the 4 or 7-position of the benzofuran ring.

Specific compounds of Formula) are given in List 1.

List 1 3- (benzo [b] furan-4-yl)-5, 6-dihydroimidazo [2, 1-b] thiazole [3-(benzo [bifuran4-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] methanol <BR> <BR> <BR> <BR> 3-(benzo [b] furan4-yl)-2-methyl-5,6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> <BR> 3- (benzo (b] furan-4-yl)-2-ethyl-5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> <BR> 3-(benzo [bifuran-5-yl)-2-methyl-5,6-dihydroimidazo [2,1-b] thiazole<BR> <BR> <BR> <BR> <BR> <BR> 3-(benzo [befuran-4-yl)-2-(methylthio)-5, 6-dihydroimidazol2, 1-blthiazole<BR> <BR> <BR> <BR> <BR> <BR> 3-(benzo [bafuran-7-yl)-2-methyl-5, 6-dihydroimidazor2, 1-b] thiazole [3- (benzo [b] furan-5-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] methanol 3-(benzo[b]furan-5-yl)-2-(1-methylethyl)-5,6-dihydroimidazo [2, 1-b]thiazole

3-(benzo [b] furan-5-yl)-2-(methylthio)-5, 6-dihydroimidazo[2,1-b] thiazole 3-(benzo[b]furan-5-yl)-2-ethyl-5,6-dihydroimidazo[2,1-b]thia zole <BR> <BR> <BR> 3- (benzo [b] furan-4-yi)-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> 3- (benzo [b] furan-4-yl)-2- {1-methylethyl)-5, 6-dihydroimidazo (2, 1-bjthiazole<BR> <BR> <BR> <BR> <BR> 3-(benzo [b] furan4-yl)-2-cyclopropyl-5,6-dihydroimidazo [2,1-b] thiazole 3-(benzo [b] furan4-yl)-2-vinyl-5, 6-dihydroimidazo [2,1-b] thiazole 1-[3-(benzo[b]furan-4-yl)-5,6-dihydroimidazo[2,1-b]thiazol-2 -yl]ethanol 2-[3-(benzo[b]furan-4-yl)-5,6-dihydroimidazo[2,1-b]thiazol-2 -yl]ethanol 3-(6-chlorobenzo [b] furan-4-yl)-2-methyl-5,6-dihydroimidazo [2, 1-b] thiazole 3- (6-chlorobenzo [b] furan-4-yl)-2-ethyf-5, 6-dihydroimidazo [2, 1-b] thiazole 3- (6-chlorobenzo[b]furan-4-yl)-2-propyl-5,6-dihydroimidazo[2,1 -b]thiazole 3-(6-chlorobenzo[b]furan-4-yl)-2-(1-methylethyl)-5,6-dihydro imidazo [2,1-b] thiazole 3- (6-chlorobenzo [b] furan-4-yl)-2-cyclopropyl-5, 6-dihydroimidazo [2,1-b] thiazole 3- (6-chlorobenzo [b] furan-4-yi)-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3- (6-chlorobenzo [b] furan-4-yl)-2- (methylthio)-5, 6-dihydroimidazo [2,1-b] thiazole [3(6-chlorobenzo[b]furan-4-yl)-5,6-dihydroimidazo[2,1-b]thia zol-2yl]methanol 1- 3- (6-chlorobenzo [b] furan-4-yi)-5, 6-dihydroimidazo [2, 1-bjthiazol-2-yljethanol 2- [3- (6-ch) orobenzo [jb] furan-4-y))-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 3- (7-chlorobenzo [b] furan-4-yl)-2-methyl-5, 6-dihydroimidazo [2,1-b] thiazole 3-(-7chlorobenzo[b]furan-4-yl)-2-ethyl-5,6-dihydroimidazo[2, 1-b]thiazole 3-(7-chlorobenzo[b]furan-4-yl)-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(7-chlorobenzo[b]furan-4-yl)-2-(1-methylethyl)-5,6-dihydro imidazo [2, 1-b] thiazole 3-(7-chlorobenzo[b]furan-4-yl)-2-cyclopropyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3- (7-chlorobenzo (b] furan-4-yl)-2-vinyl-5, 6-dihydroimidazo [2,1-b] thiazole 3-(7-chlorbenzo[b]furan-4-yl)-2-(methylthio)-5, 6-dihydroimidazo [2, 1-b] thiazole [3-(7-chlorobenzo[b]furan-4-yl)-5, 6-dihydroimidazo [2, 1-blthiazol-2-yl] methanol 1- [3- (7-chlorobenzo [b] furan-4-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] ethanol 2-[3-(7-chlorobenzo[b]furan-4-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 3-(6-fluorbenzo[b]furan-4-yl)-2-methyl-5,6-dihydroimidazol[2 ,1-b]thiazole 3- (6-fluorobenzo (b] furan-4-yi)-2-ethyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(6-fluorobenzo[b]furan-4-yl)-2-propyl-5,6-dihydroimidazo [2,1-b] thiazole 3- (6-fluorobenzo [b] furan-4-yl)-2- (1-methylethyl)-5, 6-dihydroimidazo [2,1-b] thiazole 3-(6-fluorobenzofb] furan-4-yl)-2-cyclopropyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(6-fluorbenzo[b]furan-4-yl)-2-vinyl-5,6-dihydroimidazo [2,1-b] thiazole 3-(6-fluorbenzo[b]furan-4-yl)-2-(methylthio)-5,6-dihydroimid azo[2,1-b]thiazole [3-(6-fluorbenzo[b]bfuran-4-yl)-5,6-dihydroimidazo [2, 1-b] thiazol-2-yl]methanol

1-[3-(6-fluorobenzo[b]furan-4-yl)-5,6-hydrydroimidazo [2,1-b] thiazol-2-yl] ethanol 2- [3- (6-fluorobenzojbJfuran-4-yl)-5, 6-dihydroimidazQ [2, 1-b] thiazol-2-yl] ethanol 3-(7-fluorobenzo[b]furan-4-yl)-2-methyl-5,6-dihydroimidazol[ 2,1-b]thiazole 3- (7-fluorobenzo [b] furan-4-yl)-2-ethyl-5, 6-dihydroimidazo [2,1-b] thiazole 3- (7-fluorobenzo [b] furan-4-yl)-2-propyl-5, 6-dihydroimidazo [2,1-b] thiazole 3-(7-fluorobenzo[b]furan-4-yl)-2-(1-methylenthyl)-5, 6-dihydroimidazo [2,1-b] thiazole 3- (7-fluorobenzo [b] furan-4-yl)-2-cyclopropyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(7-fluorobenzo[b]furan-4-yl)-2-vinyl-5,6-dihydroiidazo[2,1 -b]thiazole 3-(7-fluorobenzo [b] furan4-yl)-2-(methylthio)-5, 6-dihydroimidazo [2, 1-bthiazole [3-(7-fluorobenzo[b]furan-4-yl)-5,6-dihydroiidazo[2,1-b]thia zol-2-yl]methanol 1-[3-(7-fluorobenzo[b]furan-4-yl)-5,6-dihydroimidazo[2,1-b]t hiazol-2-yl]ethanol 2- [3- (7-fluorobenzo b] furan-4-yi)-5, 6-dihydroimidazo[2,1-b] thiazol-2-yl] ethanol 3- (6-methoxybenzo [b] furan-4-yl)-2-methyl-5, 6-dihydroimidazo [2,1-b3thiazole 2-ethyl-3-(6-methoxybenzo [b] furan-4-yl)-5, 6-dihydroimidazo [2, 1-bithiazole 3- (6-methoxybenzo [b] furan-4-yl)-2-propyl-5, 6-dihydroimidazo [2, 1-b]thiazole <BR> <BR> <BR> 3-(6-methoxybenzo [b3furan-4-yl)-2-(1-methylethyl)-5,6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> 2-cyclopropyl-3-(6-methoxybenzo [b] furan-4-yl)-5,6-dihydroimidazo [2,1-b] thiazole 3-(6-methoxybenzo[b]furan-4-yl)-2-vinyl-5,6-dihydroimidazo [2,1-b] thiazole 3-(6-methoxybenzolb] furan-4-yl)-2-(methylthio)-5, 6-dihydroimidazo [2,1-b] thiazole [3- (6-methoxybenzo [b] furan-4-yi)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] methanol 1-[3-(6-methoxybenzo[b]furan-4-yl)-5,6-dihydroimidazo [2,1-b] thiazol-2-yf] ethanoi 2-[3-(6-methoxybenzo[b]furan-4-yl)-5,6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 3- (7-methoxybenzo [b] furan-4-yl)-2-methyl-5, 6-dihydroimidazo [2, 1-b] thiazole 2-ethyl-3-(7-methoxybenzo[b]furan-4-yl)-5, 6-dihydroimidazo [2,1-b] thiazole 3-(7-methoxybenzo [b] furan4-yl)-2-propyl-5, 6-dihydroimidazol2, 1-b] thiazole 3- (7-methoxybenzo [blfuran-4-yl)-2- (1-methylethyl)-5, 6-dihydroimidazo [2, 1-b]thiazole 2-cyclopropyl-3- (7-methoxybenzo [b] furan-4-yl)- 5, 6-dihydroimidazo [2,1-b] thiazole 3-(7-methoxybenzo[b]furan-4-yl)-2-vinyl-5,6-dihydroimidazo[2 , 1-b] thiazole 3- (7-methoxybenzo [b] furan-4-yl)-2-(methylthio)-5, 6-dihydroimidazo [2, 1-b]thiazole [3- (7-methoxybenzo [b] furan-4-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl]methanol 1-j3- (7-methoxybenzo [b] furan-4-yl)-5, 6-dihydroimidazo[2,1-b] thiazol-2-yl] ethanol 2-[3-(7-methoxybenzo[b]furna-4-yl)-5,6-dihydroimidazo[2,1-b] thiazol-2-yl]ethanol 2-methyl-3- (2-methylbenzo [b] furan-4-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole 2-ethyl-3- (2-methylbenzo [b] furan-4-yl)- 5, 6-dihydroimidazo [2,1-b] thiazole 3-(2-methylbenzo [b] furan4-yl)-2-propyl-5, 6-dihydroimidazo[2,1-b] thiazole

3- (2-methylbenzo [b] furan-4-yi)-2- (1-methylethyl)-5, 6-dihydroimidazo [2, 1-b] thiazole 2-cyclopropyl-3-(2-methylbenzo[b]furan-4-yl)-5,6-dihydroimid azo [2,1-b] thiazole 3-(2-methylbenzo [b] furan4-yl)-2-vinyl-5,6-dihydroimidazo [2, 1-b] thiazole 3-(2-methlbenzo[b]furan-4-yl)-2-(methylthio)-5,6-dihydroimid azo[2,1-b]thiazole [3-(2-methylbenzo [b] furan4-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] methanol 1-[3-(2-methylbenzo[b]furan-4-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol <BR> <BR> <BR> <BR> 2- [3- (2-methylbenzo [b] furan-4-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yi] ethanol<BR> <BR> <BR> <BR> <BR> <BR> 2-methyl-3- (3-methylbenzo (b] furan-4-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> <BR> 2-ethyl-3- (3-methylbenzo [b] furan-4-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole 3- (3-methylbenzo b] furan-4-yl)-2-propyl-5, 6-dihydroimidazo [2,1-b] thiazole <BR> <BR> <BR> <BR> 3- (3-methyibenzo [b] furan-4-yl)-2- (1-methylethyl)-5, 6-dihydroimidazo [2, 1-b] thiazole 2-cyclopropyl-3-(3-methylbenzo [b] furan4-yl)-5, 6-dihydroimidazo[2,1-b] thiazole 3- (3-methylbenzo [b] furan-4-yl)-2-vinyl-5, 6-dihydroimidazo [2,1-b] thiazole3- (3- methylbenzo [b] furan-4-yi)-2- (methylthio)-5, 6-dihydroimidazo [2, 1-b] thiazole [3- (3-methylbenzo [bJfuran-4-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] methanol 1- (3 ; (3-methylbenzo [b] furan-4-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] ethanol 2- [3- (3-methylbenzo [b] furan-4-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 2-methyl-3-(6-methylbenzo[b]furan-4-yl)-5,6-dihydroimidazo[2 ,1-b]thiazole 2-ethyl-3-(6-methylbenzorb] furan4-yl)-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(6-methylbenzo[b]furan-4-yl)-2-propyl-5,6-dihydroimidazo [2,1-b] thiazole 3- (6-methylbenzo [b] furan-4-yl)-2- (1-methylethyl)-5, 6-dihydroimidazo [2,1-b] thiazole 2-cyclopropyl-3- (6-methylbenzo [b] furan-4-yl)- 5, 6-dihydroimidazo [2,1-b] thiazole 3-(6-methylbenzo[b]furan-4-yl)-2-vinyl-5, 6-dihydroimidazo [2,1-b] thiazole 3-(6-methylbenzo[b]furan-4-yl)-2-(methylthio)-5,6-dihydroimi dazo[2,1-b]thiazole [3-(6-methylbenzo[b]furan-4-yl)-5,6-dihydroimidazo [2,1-b] thiazol-2-yl]methanol 1- [3- (6-methylbenzo [b] furan-4-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] ethanol 2-[3-(6-methylbenzo[b]furna-4-yl)-5, 6-dihydroimidazo [2, 1-b]thiazol-2-yl]ethanol <BR> <BR> <BR> <BR> 2-methyl-3- (7-methylbenzo [b] furan-4-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> <BR> <BR> 2-ethyl-3- (7-methylbenzo [b] furan-4-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole 3-(7-methylbenzo[b]furan-4-yl)-2-propyl-5,6-dihydroimidazo[2 ,1-b]thiazole 3-(7-methylbenzo[b]furan-4-yl)-2-(1-methylethyl)-5,6-dihydro imidazo[2,1-b]thiazole 2-cyclopropyl-3- (7-methylbenzo [b] furan-4-yl)- 5, 6-dihydroimidazo [2,1-b] thiazole 3- (7-methylbenzo [b] furan-4-yl)-2-vinyl-5, 6-dihydroimidazo [2,1-b] thiazole 3- (7-methylbenzo [b] furan-4-y !)-2- (methylthio)-5, 6-dihydroimidazo [2,1-b] thiazole [3- (7-methylbenzo [b] furan-4-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl]methanol 1- [3- (7-methylbenzo (b] furan-4-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol

2-[3-(7-methylbenzo[b]furan-4-yl)-5,6-dihydroimidazo [2,1-b] thiazol-2-yl]ethanol 2-methyl-3- [6- (methylthio) benzo [b] furan-4-yi]- 5, 6-dihydroimidazo [2, 1-b] thiazole 2-ethyl-3- [6- (methylthio) benzo [b] furan4-yl]-5, 6-dihydroimidazol2, 1-b] thiazole 3- [6- (methylthio) benzo [b] furan4-yl]-2-propyl-5, 6-dihydroimidazo [2,1-b} thiazole 2-(1-methylethyl)-3-[6-(methlthio)benzo[b]furan-4-yl]-5,6-di hydroimidazo[2,1- b] thiazole 2-cyclopropyl-3- [6- (methylthio) benzo [b] furan-4-yl]-5, 6-dihydroimidazo [2, 1-b] thiazole 3- [6- (methylthio) benzo [b] furan-4-yl]-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole 2- (methylthio)-3- [6- (methylthio) benzo [b] furan-4-yi]-5, 6-dihydroimidazo [2, 1-bjthiazole [3- [6- (methylthio) benzo [b] furan-4-yl]-5, 6-dihydroimidazo[2,1-b]thiazol-2-yl]methanol 1-[3-[6-(methylthio)-benzo[b]furan-4-yl]-5,6-dihydroimidazo[ 2,1-b]thiazol-2-yl]ethanol 2- [3- [6- (methylthio) benzo [b] furan-4-yl]-5, 6-dihydroimidazo [2, 1-b]thiazol-2-yl]ethanol 2-methyl-3- [7- (methylthio) benzo [b] furan-4-yf]- 5, 6-dihydroimidazo [2, 1-b] thiazole 2-ethyl-3-[7-(methylthio)-benzo[b]furan-4-yl]- 5,6-dihydroimidazo [2,1-b] thiazole <BR> <BR> 3- [7- (methylthio) benzo [b] furan-4-yl]-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> <BR> 2- (1-methylethyl)-3- [7- (methylthio) benzo [bjfuran-4-yi]-5, 6-dihydroimidazo [2, 1- b] thiazole 2-cyclopropyl-3- [7- (methylthio) benzojb] furan-4-yi]-5, 6-dihydroimidazo [2, 1-b] thiazole 3- [7- (methylthio) benzojb] furan-4-yl]-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole 2- (methylthio)-3- [7- (methylthio) benzo [b] furan-4-yl]-5, 6-dihydroimidazo [2, 1-b] thiazole [3-[7-(methylthio)benzo[b]furan-4-yl]-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] methanol 1-[3-[7-(methylthio) benzo [b] furan-4-yl]-5, 6-dihydroimidazo [2, 1-bjthiazol-2-yl] ethanoi 2- [3- [7- (methylthio) benzo [b] furan4-yi]-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] ethanol 3- (benzo [b] furan-5-yl)-2-propyl-5, 6-dihydroimidazo [2,1-b] thiazole <BR> <BR> <BR> 3-(benzo [b] furan-5-yi)-2-cyclopropyl-5, 6-dihydroimidazol2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> 3- (benzo [b] furan-5-yl)-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole 1- [3- (benzo [b] furan-5-yi)-5, 6-dihydroimidazo [2, 1-b]thiazol-2-yl]ethanol 2- [3- (benzo [bjfuran-5-yl)-5, 6-dihydroimidazo [2, 1-b]thiazol-2-yl]ethanol 3- (7-chlorobenzo [b] furan-5-yl)-2-methyl-5, 6-dihydroimidazo[2,1-b] thiazole 3-(7-chlorobenzo[b]furan-5-yl)-2-ethyl-5,6-dihydroimidazo [2,1-b] thiazole 3- (7-chlorobenzo [b] furan-5-yl)-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(7-chlorobenzo[b]furan-5-yl)-2-(1-methylethyl)-5,6-dihydro dimidazo[2,1-b]thiazole 3-(7-chlorobenzo[b]furan-5-yl)-2-cyclopropyl-5,6-dihydroimid azo[2,1-b]thiazole 3-(7-chlorobenzo[b]furan-5-yl)-2-=vinyl-5,6-dihydroimidazo[2 ,1-b]thiazole 3-(7-chlorobenzo[b]furan-5-yl)-2-(methylthio)-5,6-dihydroimi dazo[2, 1-b] thiazole [3- (7-chlorobenzo [b] furan-5-yl)-5, 6-dihydroimidazo [2, 1-b thiazol-2-yl] methanol

1-[3-(7-chlorobenzo[b]furan-5-yl)-5,6-dihydroimidazo[2,1-b]t hiazol-2-yl]ethanol 2- [3- (7-chlorobenzo (b] furan-5-yi)-5, 6-dihydroimidazo [2,1-bJthiazoi-2-yl] ethanol 3- (7-fluorobenzo [b] furan-5-yl)-2-methyl-5, 6-dihydroimidazo [2,1-b] thiazole <BR> <BR> <BR> 3- (7-fluorobenzo [b] furan-5-yl)-2-ethyl-5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> 3- (7-fluorobenzo [b] furan-5-yl)-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(7-fluorobenzo[b]furan-5-yl)-2-(1-methylethyl)-5,6-dihydro imidazo [2,1-b] thiazofe 3- (7-fluorobenzo [b] furan-5-yl)-2-cyclopropyl-5, 6-dihydroimidazo [2,1-b] thiazole 3-(7-fluorobenzo[b]furan-5-yl)-2-vinyl-5,6-dihydroimidazol [2,1-b] thiazole 3- (7-fluorobenzo [b] furan-5-yl)-2- (methylthio)-5, 6-dihydroimidazo [2,1-b] thiazole (3- (7-fluorobenzo (b] furan-5-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] methanol 1-[3-(7-fluorobenzo[b]furan-5-yl)-5,6-dihydroiidazo [2,1-b] thiazol-2-yl]ethanol 2- [3- (7-fluorobenzo [b] furan-5-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] ethanoi 3- (7-methoxybenzo [b] furan-5-yl)-2-methyl-5, 6-dihydroimidazo[2,1-bXthiazole 2-ethyl-3-(7-methoxybenzo[b]furan-5-yl)- 5, 6-dihydroimidazo [2, 1-b]thiazole 3-(7-methoxybenzo[b]furan-5-yl)-2-propyl-5,6-dihydroimidazo[ 2,1-b]thiazole 3-(7-methoxybenzo[b]furan-5-yl)-2-(1-methylethyl)-5,6-dihydr oimidazo[2,1-b]thiazole 2-cyclopropyl-3- (7-methoxybenzo [b] furan-5-yl)- 5, 6-dihydroimidazo[2,1-b] thiazole 3-(7-methoxybenzo[b]furan-5-yl)-2-vinyl-5,6-dihydroimidazo[2 ,1-b]thiazole 3-(7-methoxybenzo[b]furan-5-yl)-2-(methylthio)-5,6-dihydroim idazo[2,1-b]thiazol <BR> <BR> <BR> (3- (7-methoxybenzo [b] furan-5-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] methanol<BR> <BR> <BR> <BR> <BR> 1- [3- (7-methoxybenzo [b] furan-5-yl)-5, 6-dihydroimidazo (2, 1-b] thiazol-2-yllethanof 2-[3-(7-methoxybenzo [b] furan-5-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 2-methyl-3- (2-methylbenzo [b] furan-5-yl)-5, 6-dihydroimidazo [2,1-b] thiazole 2-ethyl-3- (2-methylbenzo [b] furan-5-yf)- 5, 6-dihydroimidazo [2,1-b] thiazole 3-(2-methylbenzo[b]furan-5-yl)-2-propyl-5,6-dihydroimidazo [2,1-b] thiazole 3- (2-methylbenzo [bJfuran-5-yl)-2- {1-methylethyl)-5, 6-dihydroimidazo [2,1-b] thiazole 2-cyclopropyl-3-(2-methylbenzo[b]furan-5-yl)- 5,6-dihydromidazo[2,1-b]thiazole 3- (2-methylbenzo [b] furan-5-yl)-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3- (2-methylbenzo b] furan-5-yl)-2- (methylthio)-5, 6-dihydroimidazo [2, 1-b]thiazole [3- (2-methylbenzo [b] furan-5-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] methanol 1- [3- (2-methylbenzo [b] furan-5-y1)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl]ethnaol 2- [3- (2-methylbenzo [b] furan-5-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yljethanol 2-methyl-3- (3-methylbenzo [b] furan-5-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole 2-ethyl-3-(3-methylbenzo[b]furan-5-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole 3- (3-methylbenzo [b] furan-5-yl)-2-propyl-5, 6-dihydroimidazo [2, 1-b]thiazole

3-(3-methylbenzo[b]furna-5-yl)-2(1-methylethyl)-5,6-dihdroim idazo [2,1-b] thiazole 2-cyclopropyl-3-(3-methylbenzo [bfuran-5-yl)-5, 6-dihydroimidazol2, 1-b] thiazole 3- (3-methylbenzo [b] furan-5-yl)-2-vinyl-5, 6-dihydroimidazo [2,1-b] thiazole 3-(3-methylbenzo[b]furan-5-yl)-2-(methylthio)-5, 6-dihydroimidazo [2,1-b] thiazole [3- (3-methylbenzo [b] furan-5-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yljmethanol 1- [3- (3-methylbenzojb] furan-5-yl)-5, 6-dihydroimidazo [2, 1-b]thiazol-2-yl]ethanol 2- [3- (3-methylbenzo [b] furan-5-yi)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yi] ethanol 2-methyl-3-(7-methylbenzo[b]furan-5-yl)- 5,6-dihydroimidazo[2,1-b]thiazole 2-ethyl-3- (7-methylbenzo [b] furan-5-yi)- 5, 6-dihydroimidazo [2, 1-b] thiazole 3-(7-methylbenzo[b]furan-5-yl)-2propyl-5,6-dihydroimidazo[2, 1-b]thiazole 3- (7-methylbenzo [b] furan-5-yl)-2- (1-methylethyl)-5, 6-dihydroimidazo [2, 1-b] thiazole 2-cyclopropyl-3-(7-methylbenzo[b]furan-5-yl)- 5,6-dihydroimidazo[2,1-b]tiazole 3- (7-methylbenzo [b] furan-5-yl)-2-vinyl-5, 6-dihydroimidazo [2,1-b] thiazole 3-(7-methylbenzo[b]furan-5-yl)-2-(methylthio)-5,6-dihydroimi dazo[2,1-b]thiazole [3-(7-methylbenzo [b] furan-5-yl)-5, 6-dihydroimidazol2, 1-b] thiazol-2-yl] methanol 1-[3-(7-me;thylbenzo[b]furan-5-yl)-5,6-dihydroimidazo[2,1-b] thiazol-2-yl]ethanol 2- [3- 7-methylbenzojb] furan-5-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] ethanof 2-methyl-3- [7- (methylthio) benzo [b]furan-5-yl]- 5,6-dihydroimidazo [2,1-b] thiazole 2-ethyl-3- [7- (methylthi6) benzo [b] furan-5-yl]- 5, 6-dihydroimidazo [2,1-b] thiazole 3-[7-(methylthio) benzo [b] furan-5-y ]-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole 2-(1-methylethyl)-3-[7-(methylthio) benzo [b]furan-5-yl]-5,6-dihydroimidazo [2,1- b] thiazole 2-cyclopropyl-3- [7- (methylthio) benzo [b]furan-5-yl]-5,6-dihydroimidazo[2,1-b]thiazole 3- [7- (methylthio) benzo [b] furan-5-yl]-2-vinyl-5, 6-dihydroimidazo [2,1-b] thiazole 2- (methylthio)-3- [7- (methylthio) benzo [b] furan-5-yl]-5, 6-dihydroimidazo [2, 1-b] thiazole [3- [7- (methylthio) benzo [b]furan-5-yl]-5, 6-dihydroimidazo [2, 1-blthiazol-2-yl] methanol <BR> <BR> <BR> 1- [3- [7- (methyithio) benzo [blfuran-5-y ]-5, 6-dihydroimidazo [2, 1-b]3thiazol-2-yi] ethanol<BR> <BR> <BR> <BR> <BR> 2- [3- [7- (methylthio) benzo [b] furan-5-yI]-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] ethanol 3-(benzo[b]furan-6-yl)-2-methyl-5,6-dihydroiidazo[2,1-b]thia zole <BR> <BR> <BR> 3- (benzo [blfuran-6-yl)-2-ethyl-5, 6-dihydroimidazo [2, 1-blthiazole<BR> <BR> <BR> <BR> <BR> 3- (benzo [b] furan-6-yl)-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(benzo[b]furan-6-yl)-2-(1-methylethyl)-5,6-dihydroimidazo[ 2,1-b]thiazol 3- (benzo [b] furan-6-yl)-2-cyclopropyl-5, 6-dihydroimidazo [2,1-b] thiazole 3- (benzo [b] furan-6-yl)-2-vinyl-5, 6-dihydroimidazo [2, 1-b]thiazole 3-(benzo[b]furan-6-yl)-2-(methylthio)-5, 6-dihydroimidazo [2, 1-b] thiazole [3- (benzo [b] furan-6-yi)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yllmethanol

1- [3- (benzojb] furan-6-yi)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanof 2- [3- (benzo [b] furan-6-yl)-5, 6-dihydroimidazo [2, 1-b]thiazol-2-yl]ethanol 3- (4-chlorobenzo [b] furan-6-yi)-2-methyl-5, 6-dihydroimidazo [2, 1-bjthiazole 3-(4-chlorobenzojb] furan-6-yl)-2-ethyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3- (4-chlorobenzo [b] furan-6-yl)-2-propyl-5, 6-dihydroimidazo [2,1-b] thiazole <BR> <BR> <BR> 3- (4-chiorobenzo [b] furan-6-yl)-2- (1-methylethyl)-5, 6-dihydroimidazo [2, 1-b] thiazole 3- (4-chlorobenzo [b] furan-6-yl)-2-cyclopropyl-5, 6-dihydroimidazo [2, 1-b]thiazole 3- (4-chlorobenzo [b] furan-6-yi)-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(4-chorobenzo[b]furan-6-yl)-2-(methylthio)-5,6-dihydroimid azo[2,1-b]thiazole [3-(4-chlorobenzo[b]furan-6-yl)-5,6-dihydroimidazo [2,1-b] thiazol-2-yl]methyanol 1- [3- (4-chlorobenzofbjfuran-6-yl)-5, 6-dihydroimidazo [2, 1-b]thiazol-2-yl]ethanol 2-[3-(4-chlorobenzo[b]furan-6-yl)-5,6-dihydroimidazo[2,1-b]t hiazol-2-yl]ethanol 3-94-fluorobenzo[b]furan-6-yl)-2-methyl-5,6-dihydroimidazo[2 ,1-b]thiazole 3-(4-fluorobenzo[b]furan-6-yl)-2-ethyl-5,6-dihydroimidazo[2, 1-b] thiazole 3- (4-fluorobenzo [bjfuran-6-yl)-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(4-fluorobenzo[b]furan-6-yl)-2-(1-methylethyl)-5,6-dihydro imidazo[2,1-b]thiazole 3- (4-fluorobenzo [b] furan-6-yl)-2-cyclopropyl-5, 6-dihydroimidazo [2, 1-b] th iazole 3- (4-fluorobenzo [b] furan-6-yi)-2-vinyl-5, 6-dihydroimidazo [2,1-b] thiazole 3- (4-fluorobenzo [b] furan-6-yl)-2- (methylthio)-5, 6-dihydroimidazo [2, 1-b] thiazole [3- (4-fluorobenzo [b] furan-6-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] methanol 1-[3-(4-fluorobenzo[b]furan-6-yl)-5,6-dihydroimidazo[2,1-b]t hiazol-2-yl]ethanol 2- 3- (4-fluorobenzo [b] furan-6-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yllethanol 3- (4-methoxybenzo [b] furan-6-yl)-2-methyl-5, 6-dihydroimidazo [2, 1-b] thiazole 2-ethyl-3- (4-methoxybenzoEb] furan-6-yl)- 5, 6-dihydroimidazo [2, 1-6 thiazole 3-(4-methoxybenzo[b]furan-6-yl)-2-propyl-5,6-dihydroimidazo[ 2,1-b]thiazole <BR> <BR> <BR> 3- (4-methoxybenzo [b] furan-6-yl)-2- (1-methylethyl)-5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> 2-cyclopropyl-3- (4-methoxybenzo [b] furan-6-yi)- 5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> 3- (4-methoxybenzo [b] furan-6-yl)-2-vinyi-5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> 3- (4-methoxybenzo [b] furan-6-yl)-2- (methylthio)-5, 6-dihydroimidazo [2, 1-b] thiazole [3- (4-methoxybenzo [b] furan-6-yi)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yljmethanol <BR> <BR> <BR> 1- [3- (4-methoxybenzojb] furan-6-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yI] ethanol<BR> <BR> <BR> <BR> <BR> 2- [3- (4-methoxybenzo [b] furan-6-y1)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] ethano ! 2-methyl-3-(2-methylbenzo[b]furan-6-yl)- 5,6-dihydroimidazo[2,1-b]thiazole 2-ethyl-3-(2-methylbenzo[b]furan-6-yl)- 5,6-dihydroimidazo[2,1-b]thiazole 3-(2-methylbenzo[b]furan-6-yl)-2-propyl-5,6-dihydroimidazo[2 ,1-b]thiazole

3-(2-methlbenzo[b]furan-6-yl)-2-(1-methylethyl)-5,6-dihydroi midazo[2,1-b]thiazole 2-cyclopropyl-3- (2-methylbenzo [b] furan-6-yi)- 5, 6-dihydroimidazo [2, 1-b]thiazole 3-(2-methylbenzo[b]furan-6-yl)-2vinyl-5,6-dihydroimidazo[2,1 -b]thiazole 3- (2-methylbenzo [b] furan-6-yi)-2- (methylthio)-5, 6-dihydroimidazo [2, 1-b] thiazole j3- (2-methylbenzo [b] furan-6-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] methanol 1- [3- (2-methylbenzo [b] furan-6-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 2- [3- (2-methylbenzo [b] furan-6-yl)-5, 6-dihydroimidazo [2, 1-b3thiazol-2-yl] ethanol 2-methl-3-(3-methylbenzo[b]furan-6-yl)- 5,6-dihydroimidazo[2,1-b]thiazole 2-ethyl-3-(3-methylbenzo[b]furan-6-yl)- 5,6-dihydroimidazo[2,1-b]thiazole 3- (3-methylbenzo [b] furan-6-yi)-2-propyl-5, 6-dihydroimidazo [2,1-b] thiazole 3-(3-methylbenzo[b]furan-6-yl)-2-(1-methylethyl)-5,6-dihydro imidazo[2,1-b]thiazole 2-cyclopropyl-3- (3-methylbenzo [b] furan-6-yl)- 5, 6-dihydroimidazo [2,1-b]thiazole 3-(3-metylbenzo[b]furan-6-yl)-2-vinyl-5,6-dihydroimidazo [2,1-b] thiazole 3- (3-methyibenzo [b] furan-6-yl)-2- (methylthio)-5, 6-dihydroimidazo [2,1-b] thiazole [3-(3-methylbenzo[b]furan-6-yl)-5,6-dihydroimidazo[2,1-b]thi azol-2-yl]methanol 1- [3- (3-methylbenzo [b] furan-6-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yllethanol 2- [3- (3-methylbenzo [b] furan-6-yi)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 2-methyl-3- (4-methylbenzo [b] furan-6-yl)- 5, 6-dihydroimidazo [2,1-b] thiazole 2-ethyt-3- (4-methylbenzo [b] furan-6-yl)- 5, 6-dihydroimidazo[2,1-b] thiazole 3- (4-methylbenzo [b] furan-6-yl)-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(4-methylbenzo[b]furan-6-yl)-2-(1-methylethyl)-5,6-dihydro imidazo[2,1-b]tiazole 2-cyclopropyl-3-(4-methylbenzo[b]furan-6-yl)- 5,6-dihyroimidazo[2,1-b]thiazole 3-94-methylbenzo[b]furan-6-yl)-2-vinyl-5,6-dihydroimidazo[2, 1-b]thiazole 3-(4-methylbenzo[b]furan-6-yl)-2-(methylthio)-5, 6-dihydroimidazo [2,1-b] thiazole [3- (4-methylbenzo [b] furan-6-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] methanol 1- [3- (4-methylbenzo [b] furan-6-y )-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 2-[3-(4-methylbenzo[b]furan-6-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 2-methyl-3- [4- (methylthio) benzo [b] furan-6-yl]-5, 6-dihydroimidazol2, 1-b] thiazole 2-ethyl-3- [4- (methylthio) benzo [b] furan-6-yl]- 5, 6-dihydroimidazo [2,1-b] thiazole 3-[4-(methylthio)benzo[b]furan-6-yl]-2-propyl-5, 6-dihydroimidazo [2,1-b] thiazole 2- (1-methylethyl)-3- [4- (methylthio) benzo [b] furan-6-yl]-5, 6-dihydroimidazol2, 1- b]thiazole 2-cyclopropyl-3- [4- (methylthio) benzo [b] furan-6-yl]-5, 6-dihydroimidazo [2, 1-b] thiazole 3- [4- (methylthio) benzo (b] furan-6-yl]-2-vinyl-5, 6-dihydroimidazo [2, 1-blthiazole 2- (methylthio)-3- [4- (methyithio) benzo (b] furan-6-yl]-5, 6-dihydroimidazo [2, 1-b] thiazole [3- [4- (methylthio) benzo [b] furan-6-y1]-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] methanol

1- [3- [4- (methylthio) benzo [b] furan-6-yl]-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl]ethnaol 2- [3- [4- (methylthio) benzo [b]furan-6-yl]-5,6-dihydromidazo[2,1-b]thiazol-2-yl]ethanol 3-(benzo[b]furn-6-yl)-2-ethyl-5,6-dihydroimidazo[2,1-b]thiaz ole 3- (benzo [bjfuran-7-yl)-2-propyl-5, 6-dihydroimidazo[2,1-b] thiazole 3-(benzo[b]furan-7-yl)-2-(1-methylethyl)-5,6-dihydroimidazo [2, 1-b] thiazole 3-(benzo[b]furan-7-yl)-2-cyclopropyl-5,6-dihydroimidazo[2,1- b]thiazole 3-(benzo[b]furan-7-yl)-2-vinyl-5, 6-dihydroimidazo [2,1-b] thiazole 3-(benzo[b]furan-7-yl)-2-(methylthio)-5, 6-dihydroimidazo [2, 1-b] thiazole [3-(benzo[b]furan-7-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] methanol 1-[3-(benzo[b]furan-7-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl]ethanol 2- 3- (benzo [b] furan-7-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl3ethanol 3- (4-chlorobenzo [b] furan-7-yl)-2-methyl-5, 6-dihydroimidazo [2,1-b] thiazole 3- (4-chlorobenzo [b] furan-7-yl)-2-ethyl-5, 6-dihydroimidazo [2,1-b] thiazole 3- (4-chforobenzo [b] furan-7-yl)-2-propyl-5, 6-dihydroimidazo [2,1-b] thiazoie 3-(4-chlorobenzo[b]furan-7-yl)-2-(1-methylethyl)-5,6-dihydro imidazo [2,1-bjthiazole 3-(4-chlorobenzo[b]furan-7-yl)-2-cylopropyl-5,6-dihydroimida zo[2,1-b]thiazole 3-(4-chlorobenzo[b]furan-7-yl)-2-vinyl-5,6-dihydroiidazo[2,1 -b]thiazole 3- (4-chlorobenzojb] furan-7-yi)-2- (methyithio)-5, 6-dihydroimidazo [2,1-b] thiazole [3- (4-chlorobenzo [bjfuran-7-y1)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] methanol 1-[3-(4-chlorobenzo[b]furan-7-yl)-5,6-dihydroimidazo[2,1-b]t hiazol-2-yl]ethanol <BR> <BR> <BR> <BR> 2- [3- (4-chlorobenzo [b] furan-7-yi)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] ethanol<BR> <BR> <BR> <BR> <BR> <BR> 3-(5-chlorobenzolb] furan-7-yl)-2-methyl-5, 6-dihydroimidazol2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> <BR> 3- (5-chlorobenzo [b] furan-7-yi)-2-ethyi-5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> 3- (5-chlorobenzo [b] furan-7-yi)-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3- (5-chlorobenzojb] furan-7-yi)-2- (1-methylethyl)-5, 6-dihydroimidazo [2, 1-bjthiazole 3- (5-chlorobenzo [b] furan-7-yl)-2-cyclopropyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3- (5-chlorobenzo [b] furan-7-y )-2-vinyl-5, 6-dihydroimidazo[2,1-bjthiazole 3- (5-chlorobenzo (b] furan-7-yl)-2- (methylthio)-5, 6-dihydroimidazo[2,1-bjthiazole <BR> <BR> <BR> [3- (5-chlorobenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] methanol<BR> <BR> <BR> <BR> <BR> <BR> 1- 3- (5-chlorobenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] ethanol 2- [3- (5-chlorobenzo [b] furan-7-y )-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl]ethanol 3-(4-fluorobenzo[b]furany-7-yl)-2-methyl-5,6-dihydroimidazo [2,1-bJthiazole 3-(4-fluorobenzo[b]furan-7-yl)-2-ethyl-5,6-dihydroimidazo[2, 1-b]thiazole 3-(4-fluorobenzo[b]furan-7-yl)-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole

3-(4-fluorobenzolb] furan-7-yl)-2-(1-methylethyl)-5, 6-dihydroimidazo[2,1-b] thiazole 3-(4-fluorobenzo[b]furan-7-yl)-2-cyclopropyl-5,6-dihydroimid azo[2,1-b]thiazole 3- (4-fluorobenzo [b] furan-7-yl)-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(4-fluorobenzo[b]furan-7-yl)-2-(methylthio)-5, 6-dihydroimidazo [2, 1-b]thiazole [3-(4-fluorobenzo[b]furane-7-yl)-5,6-dihydroimidazo[2,1-b]th iazol-2-yl]methanol 1- [3- (4-fluorobenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2, 1-b]thiazol-2-yl]ethanol 2- [3- (4-fluorobenzo [b] furan-7-yi)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 3-(5-fluorobenzo[b]furan-7-yl)-2-methyl-5,6-dihydroimidazo [2,1-6] thiazole 3- (5-fluorobenzo [b] furan-7-yl)-2-ethyl-5, 6-dihydroimidazo[2,1-b] thiazole 3- (5-fluorobenzo [bJfuran-7-yl)-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(5-fluorobenzo[b]furan-7-yl)--2(1-methylethyl)-5,6-dihydro imidazo[2,1-b]thiazole 3- (5-fluorobenzo [b] furan-7-yl)-2-cyclopropyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(5-fluorobenzo [b3furan-7-yl)-2-vinyl-5, 6-dihydroimidazo[2,1-bjthiazole 3- (5-fluorobenzo [b] furan-7-yi)-2- (methylthio)-5, 6-dihydroimidazo [2,1-b] thiazole [3- (5-fluorobenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] methanol 1- [3- (5-fluorobenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] ethanol 2- [3- (5-fluorobenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 3-(5-methoxybenzo[b]furan-7-yl)-2-methyl-5,6-dihydroimidazo[ 2,1-b]thiazole 2-ethyl-3- (5-methoxybenzo [b] furan-7-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole 3-(5-methoxybenzo[b]furan-7-yl)-2-propyl-5,6-dihydroimidazo [2,1-b] thiazole 3-(5-methoxybenzo[b]furan-7-yl)-2-(1-methylethyl)-5,6-dihydr o9imidazo[2,1-b]thiazole <BR> <BR> <BR> 2-cyclopropyl-3- (5-methoxybenzo [b] furan-7-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> 3- (5-methoxybenzo [b] furan-7-yl)-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(5-methoxybenzo[b]furan-7-yl)-2-(methyltio)-5, 6-dihydroimidazo [2, 1-b] thiazole [3-(5-methoxybenzo[b]furan-7-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] methano ! 1- [3- (5-methoxybenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 2- [3- (5-methoxybenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 2-methyl-3-(2-methylbenzo[b]furan-7-yl)-5,6-dihydroimidazo[2 ,1-b]thiazole 2-ethyl-3-(2-methylbenzo[b]furan-7-yl)- 5,6-dihydroimidazo [2, 1-b] thiazole 3-92-methylbenzo[b]furan-7-yl)-2-propyl-5, 6-dihydroimidazo [2,1-b] thiazole 3-(2-methylbenzo[b]furan-7-yl)-2-(1-methylethyl)-5,6-dihydro imidazo [2,1-b] thiazole <BR> <BR> <BR> 2-cyclopropyl-3- (2-methylbenzo [b] furan-7-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> 3- (2-methylbenzo [b] furan-7-yl)-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(2-methylbenzo[b]furan-7-yl)-2-(methylthio)-5,6-dihydromid azol[2,1-b]thiazole <BR> <BR> <BR> [3- (2-methylbenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl] methanoi<BR> <BR> <BR> <BR> <BR> 1- [3- (2-methylbenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yllethanol

2-[3-(2-methylbenzo[b]furan-7-yl)-5,6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 2-methyl-3- (3-methylbenzo [b] furan-7-yi)- 5, 6-dihydroimidazo [2, 1-b] thiazole 2-ethyl-3- (3-methylbenzo [b] furan-7-yi)- 5, 6-dihydroimidazo [2,1-b] thiazole 3- (3-methylbenzo [b] furan-7-yl)-2-propyl-5, 6-dihydroimidazo [2,1-b] thiazole 3- (3-methylbenzo [b] furan-7-yl)-2- (1-methylethyl)-5, 6-dihydroimidazo [2,1-b] thiazole 2-cyclopropyl-3-(3-methylbenzo[b]furan-7-yl)- 5,6-dihydroimidazo [2,1-b] thiazole <BR> <BR> <BR> 3- (3-methylbenzo [b] furan-7-yl)-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole<BR> <BR> <BR> <BR> <BR> 3- (3-methylbenzo [b] furan-7-yl)-2- (methylthio)-5, 6-dihydroimidazo [2, 1-b] thiazole (3- (3-methylbenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] methanol 1- 3- (3-methylbenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yl]ethanol 2- [3- (3-methylbenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 2-methyl-3-(4-methylbenzo[b]furan-7-yl)- 5,6-dihydroimidazo[2,1-b]thiazole 2-ethyl-3- (4-methylbenzo [b] furan-7-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole 3- (4-methylbenzo [b] furan-7-yl)-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(4-methylbenoz[b]furan-7-yl)-2-(1-methylethyl)-5, 6-dihydroimidazo [2,1-b] thiazole 2-cyclopropyl-3- (4-methylbenzo [b] furan-7-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole 3- (4-methylbenzo [b] furan-7-yl)-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(4-methylbenzo[b]furan-7-yl)-2-(methylthio)-5, 6-dihydroimidazo [2,1-b] thiazole [3- (4-methylbenzo [bjfuran-7-y !)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl3methanol 1- [3- (4-methylbenzo [b] furan-7-yl)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] I-2-yl]ethanol 2-[3-(4-methylbenzo[b]furan-7-yl)-5,6-dihydroimidzo[2,1-b]th iazol-2-yl]ethanol 2-methyl-3-(5-methlbenzo[b]furan-7-yl)- 5, 6-dihydroimidazo [2,1-b] thiazole 2-ethyl-3- (5-methylbenzo [b] furan-7-yl)- 5, 6-dihydroimidazo[2,1-b] thiazole 3- (5-methylbenzo [b] furan-7-yl)-2-propyl-5, 6-dihydroimidazo [2, 1-b]thiazole 3-(5-methylbenzo[b]furan-7-yl)-2-(1-methylethyl)-5, 6-dihydroimidazo [2,1-b] thiazole 2-cyclopropyl-3- (5-methylbenzo [b] furan-7-yl)- 5, 6-dihydroimidazo [2, 1-b] thiazole 3-95-methylbenzo[b]furan-7-yl)-2-vinyl-5,6-dihydroimidazo [2,1-b] thiazole 3-(5-methylbenzo[b]furan-7-yl)-2-(methylthio)-5, 6-dihydroimidazo [2, 1-b] thiazole [3- (5-methylbenzo [b furan-7-yl)-5, 6-dihydroimidazo [2, 1-b] thiazol-2-yljmethanol 1-[3-(5-methylbenzo[b]furan-7-yl)-5,6-dihydroimidazo[2,1-b]t hiazol-2-yl]ethanol 2-j3- (5-methylbenzolb] furan-7-yi)-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl]ethanol 2-methyi-3- [4- (methylthio) benzo [b furan-7-yl]- 5, 6-dihydroimidazo [2, 1-b] thiazole 2-ethyl-3- [4- (methylthio) benzo [b] furan-7-yl]- 5, 6-dihydroimidazo [2,1-b] thiazole 3- [4- (methylthio) benzo [b] furan-7-yl]-2-propyl-5, 6-dihydroimidazo [2, 1-b] thiazole

2- (1-methylethyl)-3- [4- (methylthio) benzo [b] furan-7-yl]-5, 6-dihydroimidazo [2,1- b] thiazole 2-cyclopropyl-3-[4-(methylthio)benzo[b]furan-7-yl]-5, 6-dihydroimidazo [2, 1-b] thiazole 3- (4- (methylthio) benzo [b] furan-7-yl]-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole 2- (methylthio)-3- [4- (methyithio) benzojb] furan-7-yi]-5, 6-dihydroimidazo [2,1-b] thiazole [3-[4-(methylthio)benzo[b]furan-7-yl]-5, 6-dihydroimidazo [2, 1-b]thiazol-2-yl]methanol 1- [3- [4- (methylthio) benzo [b] furan-7-yl]-5, 6-dihydroimidazo [2, 1-b]thiazol-2-yl]ethanol 2- [3- [4- (methyithio) benzo {b] furan-7-yt]-5, 6-dihydroimidazo [2,1-b] thiazol-2-yljethanol 2-methyl-3-[5-(methylthio)benzo[b]furan-7-yl]- 5,6-dihydroimidazo [2,1-b] thiazole 2-ethyl-3- [5- (methylthio) benzo [b] furan-7-yI]- 5, 6-dihydroimidazo [2, 1-b] thiazole 3-[5-(methylthio)benzo[b]furan-7-yl]-2-propyl-5,6-dihydroimi dazo[2, 1-b] thiazole 2- (1-methylethyl)-3- [5- (methylthio) benzo [bjfuran-7-yl]-5, 6-dihydroimidazo [2, 1- b]thiazole 2-cycloprpyl-3-[5-(methylthio)benzo[b]furan-7-yl]-,56-dihydr oimdazo[2,1-b]thiaozle 3- [5- (methylthio) benzo [b] furan-7-yl]-2-vinyl-5, 6-dihydroimidazo [2, 1-b] thiazole 2- (methylthio)-3- [5- (methylthio) benzo [b] furan-7-yl]-5, 6-dihydroimidazo [2,1-b] thiazole [3- [5- (methylthio) benzo [b] furan-7-yl]-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] methanol 1- [3- [5- (methylthio) benzo [b] furan-7-yi]-5, 6-dihydroimidazo [2,1-b] thiazol-2-yl] ethanol 2- [3- [5- (methylthio) berizo [b] furan-7-yl]-5, 6-dihydroimidazo [2,1-b]thiazol-2-yl]ethanol including pharmaceutically acceptable salts thereof and individual enantiomers, racemates or other mixtures of enantiomers.

Particularly preferred compounds are the following : 3-(benzo[b]furan-7-yl)-2-methyl-5, 6-dihydroimidazo [2, 1-b] thiazole 3-(benzo[b]furan-4-yl)-2-methyl-5, 6-dihydroimidazo [2,1-b] thiazole including pharmaceutically acceptabie salts thereof and individual enantiomers, racemates or other mixtures of enantiomers.

The present invention also includes pharmaceutical compositions comprising a therapeutically effective amount of a compound of Formula) or a salt thereof together with a pharmaceutical acceptable diluent or carrier.

As used hereinafter, the term"active compound"denotes a compound of Formula t or a salt thereof. In therapeutic use, the active compound may be administered orally, rectally, parenterally or topically, preferably orally. Thus the therapeutic compositions of the present invention may take the form of any of the known pharmaceutical compositions for oral, rectal, parenteral or topical administration. Pharmaceutically acceptable carriers suitable for use in such compositions are well known in the art of pharmacy. The compositions of the invention may contain 0.1-99% by weight of active compound. The compositions of the invention are generally prepared in unit dosage form. Preferably the unit dosage of active ingredient is 1-500 mg. The excipients used in the preparation of these compositions are the excipients known in the pharmacist's art.

Compositions for oral administration are the preferred compositions of the invention and these are the known pharmaceutical 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 pharmacist's art. Tablets may be prepared by mixing the active compound with an inert diluent such as calcium phosphate in the presence of disintegrating agents, for example maize starch, and lubricating agents, for example magnesium stearate, and tableting the mixture by known methods. The tablets may 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. Such tablets may, 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 gelatin capsules, containing the active compound with or without added excipients, may be prepared by conventional means and, if desired, provided with enteric coatings in a known manner. The tablets and capsules may conveniently each contain 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 a suitable vegetable oil, for example arachis oil.

Preferably the compositions of the invention are administered orally in the known pharmaceutical forms for such administration. Dosage forms suitable for oral administration may comprise tablets, pills, capsules, caplets, multiparticulates

including: granules, beads, pellets and micro-encapsulated particles ; powders, elixirs, syrups, suspensions and solutions.

Solid oral dosage forms, for example tablets, may be prepared by mixing the pharmaceutical composition of the present invention with one or more of the following ingredients or mixtures thereof : inert diluents, for example calcium carbonate, calcium sulphate, compressible sugar, confectioner's sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, glyceryl palmitostearate, hydrogenated vegetable oil, kaolin, lactose, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, microcrystalline cellulose, polymethacrylates, potassium chloride, powdered cellulose, pregelatinized starch, sodium chloride, sorbitol, starch, sucrose, sugar spheres, talc and tribasic calcium phosphate; disintegrating agents, for example alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium, crospovidone, guar gum, magnesium aluminium silicate, methylcellulose, microcrystalline cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate, sodium starch glycolat, starch including maize starch and agar; lubricating agents, for example calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated. vegetable oil, light mineral oil, magnesium stearate, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulphate, sodium stearyl fumarate, stearic acid, talc and zinc stearate ; binders, for example acacia, alginic acid, carbomer, carboxymethylcellulose sodium, dextrin, ethyfcellulose, gelatin, guar gum, hydrogenated vegetable oil, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, liquid glucose, magnesium aluminium silicate, maltodextrin, methylcellulose, polymethacrylates, povidone, pregelatinized starch, sodium alginate, starch including maize starch, zein, sugars (such as sucrose, molasses and lactose), and natural and synthetic gums (such as extract of Irish moss, polyethylene glycol, waxes, microcrystalline cellulose and poiyvinylpyrrolidone) ; colouring agents, for example conventional pharmaceutically acceptable dyes; sweetening and flavouring agents; preservatives;

one or more pharmaceutical acceptable couple or couples (such as those comprising an acid and a carbonate or bicarbonate salt), which effervesces to aid dissolution when the solid dosage form is added to water; and other optional ingredients known in the art to permit production of oral dosage forms by known methods such as tabletting.

Solid oral dosage forms may be formulated in a manner known to those skilled in the art so as to give a sustained release of the active compound. Film coated, solid oral dosage forms comprising compositions of the present invention may be advantageous, depending on the nature of the active compound. Various materials, for example shellac and/or sugar, may be present as coatings, or to otherwise modify the physical form of the oral dosage form. For example tablets or pills may, if desired, be provided with enteric coatings by known methods, for example by the use of cellulose acetate phthalate and/or hydroxy propyl methylcellulose phthalate.

Capsules and/or capiets (for example hard or soft gelatin capsules) comprising the active compound (with or without added excipients such as a fatty oil), may be prepared by conventional means and, if desired, provided with enteric coatings in a known manner. The contents of the capsule and/or caplet may be formulated using known methods to give sustained release of the active compound.

Liquid oral dosage forms comprising compositions of the present invention may be an elixir, suspension and/or syrup (for example, aqueous suspensions containing the active compound in an aqueous medium in the presence of a non- toxic suspending agent [such as sodium carboxymethylcelfulose] and/or oily suspensions containing the active compound in a suitable vegetable oil [such as arachis oil and/or sunflower oil]). Liquid oral dosage forms may also comprise one or more sweetening agent, flavouring agent, preservatives and/or mixtures thereof.

The active compound may be formulated into granules with or without additional excipients. The granules may be ingested directly by the patient or they may be added to a suitable liquid carrier (for example water) before ingestion. The granules may contain disintegrants (for example a pharmaceutical acceptable effervescent couple formed from an acid and a carbonate or bicarbonate salt) to facilitate dispersion in the liquid medium.

Preferably each of the above oral dosage forms may contain from about 1 mg to about 1000 mg, more preferably from about 5 mg to about 500 mg (for example 10 mg, 50 mg, 100 mg, 200 mg, or 400 mg) of the active compound.

Compositions of the invention suitable for rectal administration are the known pharmaceutical forms for such administration, for example, suppositories with hard fat, semi-synthetic glyceride, cocoa butter and/or polyethylene glycol bases.

Pharmaceutical compositions may also be administered parenterally (for example subcutaneously, intramuscularly, intradermally and/or intravenously [such as by injection and/or infusion3 in the known pharmaceutical dosage forms for parenteral administration (for example sterile suspensions in aqueous and/or oily media and/or sterile solutions in suitable solvents, preferably isotonic with the blood of the intended patient). Parenteral dosage forms may be sterilised (for example by micro-filtration and/or using suitable sterilising agents [such as ethylene oxide]).

Optionally one or more of the following pharmaceutically acceptable adjuvants suitable for parenteral administration may be added to parenteral dosage forms: local anaesthethetics, preservatives, buffering agents and/or mixtures thereof.

Parenteral dosage forms may be stored in suitable sterile sealed containers (for example ampoules and/or vials) until use. To enhance stability during storage the parenteral dosage form may be frozen after filling the container and fluid (for example water) may be removed under reduced pressure.

Pharmaceutical compositions may be administered nasally in known pharmaceutical forms for such administration (for example sprays, aerosols, nebulised solutions and/or powders). Metered dose systems known to those skilled in the art (for example aerosols and/or inhalers) may be used.

Pharmaceutical compositions may be administered to the buccal cavity (for example sub-lingually) in known pharmaceutical forms for such administration (for example slow dissolving tablets, chewing gums, troches, lozenges, pastilles, gels, pastes, mouthwashes, rinses and/or powders).

Compositions for topical administration may comprise a matrix in which the pharmacologically active compounds of the present invention are dispersed so that

the compounds are held in contact with the skin in order to administer the compounds transdermally. A suitable transdermal composition may be prepared by mixing the pharmaceutical active compound with a topical vehicle, such as a mineral oil, petrolatum and/or a wax, for example paraffin wax or beeswax, together with a potential transdermal accelerant such as dimethyl sulphoxide or propylene glycol. Alternatively the active compounds may be dispersed in a pharmaceutical acceptable cream or ointment base. The amount of active compound contained in a topical formulation should be such that a therapeutically effective amount of the compound is delivered during the period of time for which the topical formulation is intended to be on the skin.

The compounds of the present invention may also be administered by continuous infusion either from an external source, for example by intravenous infusion or from a source of the compound placed within the body. Internal sources include 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 a very sparingly water-soluble derivative such as a dodecanoate salt or (b) solid in the form of an implanted support, for example of a synthetic resin or waxy material, for the compound to be infused. The support may be a single body containing all the compound or a series of several bodies each containing part of the compound to be delivered. The amount of active compound present in an internal source should be such that a therapeuticaily effective amount of the compound is delivered over a long period of time. in some formulations it may be beneficial to use the compounds of the present invention in the form of particles of very small size, for example as obtained by fluid energy milling.

In the compositions of the present invention the active compound may, if desired, be associated with other compatible pharmacologically active ingredients.

The present invention also comprises a compound of Formula I for use as a medicament.

The pharmaceutical compositions containing a therapeutical effective amount of a compound of Formula) may be used to treat depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, obsessive-compulsive behaviour, panic attacks, social phobias, eating disorders such as bulimia, anorexia, snacking and binge eating, non-insulin dependent diabetes mellitus, hyperglycaemia, hyperlipidaemia, stress in mammals particularly humans, as an aid to smoking cessation in human beings and in the treatment and/or prophylaxis of seizures, neurological disorders such as epilepsy and/or conditions in which there is neurological damage such as stroke, brain trauma, cerebral ischaemia, head injuries and haemorrhage. Whilst the precise amount of 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 always lies within the sound discretion of the administering physician, the amount of active compound administered per day is in the range 1 to 1000 mg preferably 5 to 500 mg given in single or divided doses at one or more times during the day.

In yet another aspect, the present invention provides the use of a compound of Formula I in the manufacture of a medicament for use in the treatment of depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, obsessive-compulsive behaviour, panic attacks, social phobias, eating disorders such as bulimia, anorexia, snacking and binge eating, non-insulin dependent diabetes mellitus, hyperglycaemia, hyperlipidaemia, stress, as an aid to smoking cessation and in the treatment and/orprophylaxis of seizures, neurological disorders such as epilepsy and/or conditions in which there is neurological damage such as stroke, brain trauma, cerebral ischaemia, head injuries and haemorrhage.

The present invention also provides a method of treating depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, obesity, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, obsessive-compulsive behaviour, panic attacks, social phobias, eating disorders such as bulimia, anorexia, snacking and binge eating, non-insulin dependent diabetes mellitus, hyperglycaemia, hyperiipidaemia, stress and seizures, neurological disorders such as epilepsy and/or conditions in which there is neurological damage such as stroke, brain trauma, cerebral ischaemia, head injuries and haemorrhage which comprises the

administration of a therapeutical effective amount of a compound of Formula I to a patient in need thereof.

The present invention also provides a method of reducing the craving to smoke in human beings which comprises the administration of a therapeutical effective amount of a compound of Formula t to a patient in need thereof. The present invention also provides a method of reducing weight gain after smoking cessation in human beings which comprises the administration of a therapeutical effective amount of a compound of Formula I to a patient in need thereof.

In addition the compounds of the present invention may be useful in the treatment or prevention of metabolic diseases and conditions arising therefrom, for example non exercise activity thermogenesis and increased metabolic rate, sexual dysfunction, sleep apnoea, premenstrual syndrome, urinary incontinence, hyperactivity disorders, hiatial hernia and reflux esophagitis, pain, especially neuropathic pain, weight gain associated with drug treatment, chronic fatigue syndrome, osteoarthritis and gout, cancers associated with weight gain, menstrual dysfunction, gallstones, orthostatic hypotension and pulmonary hypertension.

The compounds of the present invention may be useful in preventing cardio- vascular disease, and in reducing platelet adhesiveness, in aiding weight loss after pregnancy and in aiding weight loss after smoking cessation.

Processes for the preparation of compounds of Formula I will now be described. The processes may be performed on an individual basis, or by multiple parallel synthesis, also known as High Speed Analoguing. The processes are preferably carried out at atmospheric pressure.

Compounds of Formula I may be prepared by methods analogous to those disclosed in WO 97/02269. Additionally compounds of Formula I may be prepared by methods described below.

Compounds of Formula I may be prepared by dehydrating a compound of FormulaVI

in which RI, R2, g and n are as hereinbefore defined, optionally in the presence of an acid, for example acetic or sulphuric acid, and optionally in the presence of a second dehydrating agent, for example acetic anhydride, at a temperature in the range 0- 200°C ; preferably in the range 20-150°C.

Compounds of Formula VI may be prepared by reacting a compound of Formula VII in which n is as hereinbefore defined, with a compound of Formula VIII in which Z is a leaving group, for example a halo such as bromo, and Rr, R2 and g are as hereinbefore defined, at a temperature in the range 0-200°C, in the presence of a solvent, for example ethanol and optionally in the presence of an acid, for

example acetic acid. ; preferably by heating at a temperature in the range 20°C to the boiling point of the solvent used.

Compounds of Formula I may also be prepared directly by reacting a compound of Formula Vil with a compound of Formula VIII at a temperature in the range of 0-200°C, optionally in the presence of an acid, for example acetic acid, and optionally in the presence of a solvent, for example ethanol, without isolation of the intermediate of Formula Vf ; preferably by heating at a temperature in the range 20-150°C.

Compounds of Formula Vlil in which Z is halo may be prepared by reaction of a compound of Formula IX in which Ri, Ra and g are as hereinbefore defined, with a halogenating agent, for example a brominating agent such as phenyltrimethylammonium tribromide or copper (ll) bromide, at a temperature in the range 0-200°C in the presence of a solvent, for example tetrahydrofuran; preferably at a temperature in the range 20- 150°C.

Compounds of Formula IX may be prepared by the reaction of a compound of Formula X in which Ri and g are as hereinbefore defined with an organometallic reagent, for example a compound of formula R2CH2MgX in which R2 is as hereinbefore defined and X is halo, for example bromo, in the presence of a solvent, for example t tetrahydrofuran or ether, at a temperature in the range of-50°C to the boiling point of

the solvent used, followed by hydrolysis of the intermediate imine salt optionally in the presence of an acid catalyst, for example hydrochloric acid.

Compounds of Formula X in which the cyano-group is attached at the 4- position of the benzo [b] furan may be prepared by the reaction of a compound of Formula XI in which Ri and g are as hereinbefore defined with an oxidising agent such as 2,3- dichloro-5, 6-dicyano-1,4-benzoquinone, in the presence of a solvent, for example toluene, at a temperature in the range of 0°C to the boiling point of the solvent used.

Compounds of Formula Xi may be prepared by the reaction of a compound of Formula Xll in which Ri and g are as hereinbefore defined with a source of cyanide, for example trimethylsilyl cyanide, optionally in the presence of an acid, for example a Lewis acid such as boron trifluoride etherate, and optionally in the presence a solvent, for example toluene, at a temperature in the range of 0-250°C, followed by reaction with a reagent capable of generating a double bond, for example phosphorous oxychloride, or an acid, such as 4-toluenesulphonic acid, optionally in the presence of a solvent, for example toluene, at a temperature in the range of 0-250°C.

The methods described above to prepare compounds of Formula X in which Ri and g are as hereinbefore defined in which the cyano-group is attached at the 4- position of benzo [b] furan may be used to prepare compounds of Formula X in which

the cyano-group is attached at the 5-, 6-or 7-position by starting from the appropriate dihydrobenzo[b]furanone having the Formula XIII, XIV or XV Compounds of Formula I in which R2 represents halo may be prepared by reacting a compound of Formula XVI in which R1, n and g. are as hereinbefore defined, with a halogenating agent for example bromine, phenyltrimethylammonium tribromide or benzyltrimethyl- ammonium tetrachloroiodate at a temperature in the range-50-200°C optionally in the presence of a solvent, for example dichtoromethane, tetrahydrofuran or acetone.

Compounds of Formula I in which R2 represents a group of Formula -CH (OH) Rx in which Rx is a C1. 5 alkyl group, an alkenyl group containing 2-5 carbon atoms, an alkynyl group containing 2-5 carbon atoms or an aryl group may be prepared by reacting a compound of Formula XVII in which Ri, n and g are as hereinbefore defined and Ry is H with an organometallic reagent, for example a compound of formula RXMgX or RXLi in which Rx is as hereinbefore defined and X is halo, for example bromo, in the presence of a solvent, for example tetrahydrofuran or ether, at a temperature in the range of-50°C to the boiling point of the solvent used.

Compounds of Formula I in which R2 represents a group of Formula -CH (OH) Ry in which Ry is a Cl-5 alkyl group, an alkenyl group containing 2-5 carbon atoms, an alkynyl group containing 2-5 carbon atoms or an aryl group may be prepared. by reacting a compound of Formula XVII in which R1, n and g are as hereinbefore defined and Ry is a C1-5 alkyl group, an alkenyl group containing 2-5 carbon atoms, an alkynyl group containing 2-5 carbon atoms or an aryl group with a reducing agent, for example sodium borohydride, in the presence of a solvent, for example ethanol, at a temperature in the range of 0°C to the boiling point of the solvent used.

Compounds of Formula I in which R2 is hydroxymethyl may be prepared by reacting a compound of Formula XVII in which Ri, n and g are as hereinbefore defined and Ry is H with a reducing agent, for example sodium borohydride, in a

solvent, for example methanol, at a temperature in the range of-50°C to the boiling point of the solvent used.

Compounds of Formula) in which R2 represents a group of Formula -CH2Rx in which Rx is H or a C,. 5 alkyl group may be prepared by reacting a compound of Formula XVII in which R1, n and g are as hereinbefore defined and Ry is H or a C15 alkyl group with a reducing agent, for example borane-dimethylamine complex, in the presence of a Lewis acid catalyst, for example aluminium chloride, and a solvent, for example dichloromethane, at a temperature in the range of-50°C to the boiling point of the solvent used.

Compounds of Formula I in which R2 is hydroxyiminomethyl may be prepared by reacting a compound of Formula XVII in which RI, n and g are as hereinbefore defined and Ry is H with hydroxylamine or a salt thereof optionally in the presence of a solvent, for example an alcohol, eg ethanol, at a temperature in the range of 0- 250°C.

Compounds of. Formula) in which Rz tscyano may be prepared by reacting a compound of Formula XVII in which Ri, n and g are ashereinbefore defined and Ry is H with hydroxylamine or a salt thereof in the presence of formic acid at a temperature in the range of 0-250°C.

Compounds of Formula I in which R2 represents a C1-4alkyliminomethylene group may be prepared by reacting a compound of Formula XVII in which Ra, n and g are as hereinbefore defined and Ry represents hydrogen with an amine of formula RaNH2 wherein Ra represents a C1-4 alkyl group optionally in the presence of a solvent, for example an alcohol e. g. ethanol, optionally in the presence of an acid catalyst for example, acetic acid, at a temperature in the range 0-250°C.

Compounds of Formula I in which R2 represents a C1-4alkylaminomethylene group may be prepared by reacting a compound of Formula I in which R2represents a C1-4alkylimonomethylene group with a reducing agent, for example sodium borohydride, in the presence of a solvent, for example an alcohol e. g. ethanol, at a temperature in the range 0°C to the boiling point of the solvent used.

Compounds of Formula) in which R2 represents a Calkylaminomethylene group may be prepared directly from a compound of Formula XVII in which R1, n and g are as hereinbefore defined and Ry represents hydrogen by reaction with an amine of formula RaNH2 wherein Ra represents a C1-4 alkyl group and a reducing agent, for example sodium triacetoxyborohydride, in the presence of a solvent, for example tetrahydrofuran, at a temperature in the range 0°C to the boiling point of the solvent used.

Compounds of Formula I in which R2 represents a group of formula -C (OH) RxRy in which Rx and Ry are each independently a C1. 5 alkyl group may be prepared by reacting a compound of Formula XVII in which Ry is a Ci-s alkyl group with an organometallic reagent, for example a compound of formula RxMgX or RxLi in which Rx is as hereinbefore defined and X is halo, for example bromo, in the presence of a solvent, for example tetrahydrofuran or ether, at a temperature in the range of-50°C to the boiling point of the solvent used.

Compounds of Formula I in which R2 represents a group of formula -C (OH) RxRy in which Rx and Ry are the same C1-2 alkyl group may be prepared by reacting a compound of Formula XVII, as hereinbefore defined except that Ry is ORz in which Rz is a C1-6alkyl group, with an organometallic reagent, for example a compound of formula RxMgX or RXLi in which Rx is as hereinbefore defined and X is halo, for example bromo, in the presence of a solvent, for exampletetrahydrofuran or ether, at a temperature in the range of-50°C to the boiling point of the solvent used.

Compounds of Formula I in which R2 represents a C2-6alkenyl group in which the double bond is attached to the carbon alpha to the thiazole ring or a styryl group may be prepared by reacting compounds of Formula XVII, in which Ry represents hydrogen or a C1-4 alkyl group, with a phosphonium salt of formula RzPh3P+Br-or a phosphonate of formula RPO (OEt) 2 in which Rz represents a Cl-5 alkyl group or a benzyl group in the presence of a base, for example n-butyllithium or sodium hydride, in a solvent, for example an ether, e. g. tetrahydrofuran, at a temperature in the range-78°C to the boiling point of the solvent used.

Compounds of Formula I in which R2 represents a C2-6 alkanol group may be prepared by reacting a compound of Formula I in which R2 represents halo, for

example bromo or chloro, or a compound of Formula XVI, with a metallating agent for example a compound of formula RbMgX or RbLi in which Rb is a C14 alkyl group and X is halo, for example bromo or chloro, in the presence of a solvent, for example an ether, eg diethyl ether or tetrahydrofuran, at a temperature in the range-78°C to the boiling point of the solvent used, and then reacting the product obtained with an acylating agent for example a compound of Formula RcCON (CH3) OCH3in which Rc represents a Cl. 5 alkyl group in a solvent, for example an ether e. g. tetrahydrofuran, at a temperature in the range 0°C to the boiling point of the solvent used.

Compounds of Formula XVII may be prepared in a similar manner.

Compounds of Formula I in which R2 represents a C1-3alkoxyC1-3 alkyl group may be prepared by reacting a compound of Formula I in which R2 represents a hydroxyC1 3 alkyl group with a C1-3 alkylating agent, for example a C1-3 alkyl halide e. g. a CI-3 alkyl iodide, in the presence of a base, for example sodium hydride, in a solvent, for example N, N-dimethylformamide, at a temperature in the range of-50 to 150°C.

Compounds of Formula I in which R2 represents a c3-6cloalkoxy C1-3 alkyl group may be prepared by reacting a compound of Formula I in which R2 represents a hydroxyC1-3 alkyl group with a C3-6cyloalkylating agent, for example a C3- 6cycloalkyl halide e. g. a C3-6cycloalkyl iodide, in the presence of a base, for example sodium hydride, in a solvent, for example N,N-dimethylformamide, at a temperature in the range of-50 to 150°C.

Compounds of Formula I in which R2 represents a C4.

7cycloalkylalkoxyC1-3alkyl group may be prepared by reacting a compound of Formula I in which R2 represents a hydroxyC1-3 alkyl group with a C4-7 cycloalkylalkylating agent, for example a C4-7cycloalkylalkyl halide e. g. a ¬4-7 cycloalkylalkyl iodide in the presence of a base, for example sodium hydride, in a solvent, for example NN-dimethylformamide, at a temperature in the range of-50 to 150°C.

Compounds of Formula I in which Rz represents a C-37alkynylakoxyC1-3alkyl group may be prepared by reacting a compound of Formula I in which R2 represents

a hydroxyC1-3 alkyl group with a C3-7 alkynylalkylating agent, for example a ¬3. 7 alkynylalkyl halide e. g. a C3. 7 alkynylalkyi iodide in the presence of a base, for example sodium hydride, in a solvent, for example N, N-dimethylformamide, at a temperature in the range of-50 to 150°C.

Compounds of Formula i in which R2 represents a C1-3alkylthioC1-3alkyl group may be prepared by reacting a compound of Formula I in which R2represents a mercaptoC1-3 alkyl group with a C1-3 alkylating agent, for example a CI-3 alkyl halide e. g. a CI-3 alkyl iodide in the presence of a base, for example sodium hydride or sodium hydroxide, in a solvent, for example N, N-dimethylformamide, at a temperature in the range of-50 to 150°C.

Compounds of Formula I in which R2 represents a C1-3 alkylthio group or an arylthio group and RI, n and g are as previously defined may be prepared by reacting a compound of Formula I in which Rz represents haJo, or a compound of Formula XVI, with a metallating agent, for example a compound of formula RMgX or RLi in which R is a C1-6 alkyl group and X is halo, for example chloro, bromo or iodo, in a solvent, for example an ether or a mixture of ethers, eg tetrahydrofuran or diethyl ether, at a temperature in the range of-100°C to the boiling point of the solvent used to give an intermediate complex, which is reacted with a disulphide of formula RdS-SRd in which Rd is a C1-3 alkyl group or an aryl group, at a temperature in the range of -100°C to the boiling point of the solvent used.

Compounds of Formula I in which R2 represents a C1-3 alkoxy group and R1, n and g are as previously defined may be prepared by reacting a compound of Formula I in which R2 represents halo, for example bromo or iodo, with a CI-3 alkoxide salt, for example a sodium or potassium salt, optionally in the presence of a solvent, for example a C1-3 alcohol or dimethylformamide, optionally in the presence of a catalyst, for example a copper (1) salut, at a temperature in the range of 0-350°C.

Compounds of Formula Vil are commercially available. Compounds of Formula VIII, IX, XII, XIII, XIV and XV may be prepared by methods known to those skilled in the art and as specified in the individual Examples described herein.

The ability of compounds of Formula I to interact with 5-hydroxytryptamine (5-HT) receptors has been demonstrated for the products of Examples 1 to 3 by the following test which determines the ability of the compounds to inhibit tritiated ligand binding to 5-HT receptors in vitro and in particular to 5-HT1A receptors.

Hippocampal tissue from the brains of male Sprague-Dawley rats (Charles River; weight range 150-250 g) was homogenised in ice-cold 50 mM Tris-HCI buffer (pH 7.7 when measured at 25°C, 1: 40 w/v) and centrifuged at 40,000 g at 4°C for 10 minutes. The pellet was rehomogenised in the same buffer, incubated at 37°C for 10 minutes and centrifuged at 40,000 g at 4°C for 10 minutes. The final pellet was resuspended in 50 mM Tris-HCI buffer (pH 7.7) containing 4 mM Cal2, 0.1% L-ascorbic acid and 10 uM pargyline hydrochloride (equivalent to 6.25 mg wet weight of tissue/ml) and used immediately in the binding assay.

Membranes (400 Al ; equivalent to 2.5 mg wet weight of tissue/tube) were incubated with 50 Al of [3H]8-hydroxy-2-(dipropylamino)tetralin ([3H]8-OH-DPAT) at a single concentration of 1 nM and Sû, ul of distiffed water (total binding) or 50 111 of test compound (at a single concentration of 104 M or at 10 concentrations ranging from 10-1'-10-3 M) or 50, al of 5-HT (10 ; nM, non-specific binding) at 25°C for 30 minutes.

The incubation was terminated by rapid filtration under vacuum through Skatron 11734 filters using a Skatron Cell Harvester. Filters were washed with ice-cold 50 mM Tris-HCI buffer, pH 7.7 (at 25°C, wash setting 9,9,0). The scored filter paper discs were punched out into vials, scintillation fluid added and radioactivity determined by liquid scintillation counting.

The ability of compounds of Formula 1 to interact with 5-hydroxytryptamine (5-HT) reuptake sites has been demonstrated for the products of Examples 1 to 3 by the following test which determines the ability of compounds to displace the standard ligand, [3H] citalopram, from 5-HT reuptake sites in vitro.

Frontal cortical tissue from the brains of male Charles River rats weighing 150-250 g was homogenised in ice-cold 50 mM Tris-HCI, pH 7.4 (when measured at 25°C) containing 120 mM sodium chloride and 5 mM potassium chloride (Tris buffer; 1: 30 w/v) and centrifuged at 40,000' g for 10 minutes. The supernatant was

discarded and the pellet rehomogenised in Tris buffer, 1: 60 w/v, and centrifuged at 40,000 g for 10 minutes. This step was repeated a further time. The final pellet was resuspended in 50 mM Tris-HCI, pH 7.4 containing 120 mM sodium chloride and 5 mM potassium chloride (equivalent to 3.125 mg wet weight of tissue/ml) and used immediately in the binding assay. All centrifugations were performed at 4°C.

Membranes (400 fil ; equivalent to 1. 25 mg wet weight of tissue/tube) were incubated with 50 ul [3H] citalopram at a single concentration of 1.3 nM and 50 ul of distilled water (total binding) or 50 pLI of test compound (at a single concentration of 1 a M or at 10 concentrations ranging from 10 « 10-3 M) or 50, ul of paroxetine (0.5 I1M ; non-specific binding) for 1 h at 27°C. Membrane bound radioactivity was recovered by filtration under vacuum through Skatron 11734 filters presoaked in 0.5% PEI using a Skatron Cell Harvester. Filters were then washed in ice-cold 50 mM Tris-HCI buffer, pH 7.4 (at 25°C, wash setting 9,9,0). The scored filter paper discs were punched out into vials, scintillation fluid added and radioactivity determined by liquid scintillation counting.

The ability of compounds of Formula I to interact with noradrenaline (NA) reuptake sites has been demonstrated for the products of Examples 1 to 3 by the following test which determines the ability of compounds to displace the standard ligand, [3H] nisoxetine, from noradrenaline reuptake sites in vitro.

Frontal cortical tissue from the brains of male Charles River rats weighing 150-250 g was homogenised in ice-cold 50 mM Tris-HCI, pH 7.4 (at 25°C) containing 120 mM sodium chloride and 5 mM potassium chloride (Tris buffer; 1: 60 w/v) using a Kinematic poltron (speed setting 6 for 10 seconds) and centrifuged at 40,000 g for 10 minutes. The supernatant was discarded and the pellet rehomogenised in Tris buffer, 1: 60 w/v, and centrifuged at 40,000 g for 10 minutes. This step was repeated twice more so that, in total, the brain tissue was homogenised and centrifuged four times. The final pellet was resuspended in 50 mM Tris-HCI, pH 7.4 containing 300 mM sodium chloride and 5 mM potassium chloride (equivalent to 18.75 mg wet weight of tissue/ml) and used immediately in the binding assay. All centrifugations were performed at 4°C.

Membranes (400 pI ; equivalent to 7.5 mg wet weight of tissue/tube) were incubated with 50 µl [3H] nisoxetine at a single concentration of 0.6 nM and 50 pti of distilled water (total binding) or 50 ; nt of test compound (at a single concentration 10 M or at 10 concentrations ranging from 10-11-10-3 M) or 50 pl of mazindol (1 gM ; non-specific binding) for 4 h at 4°C. Membrane bound radioactivity was recovered by filtration under vacuum through Skatron 11734 filters using a Skatron cell harvester. Filters were rapidly washed with ice-cold 50 mM Tris-HCI, pH 7.4 containing 120 mM sodium chloride and 5 mM potassium chloride (wash setting 9,9,0). The scored filter paper discs were punched out into vials, scintillation fluid added and radioactivity determined by liquid scintillation counting.

The ability of compounds of Formula I to interact with muscarinic receptors has been demonstrated for the products of Examples 1-3 by the following test which determines the ability of compounds to displace the standard ligand, [3H] N-methylscopolamine, from muscarinic receptors in vitro.

Frontal cortical tissue from the brains of male Charles River rats weighing 150-250 g was homogenised in ice-cold 20 mM HEPES buffer, pH 7.5 (measured at 25°C) containing 100 mM sodium chloride and 10 mM magnesium chloride (1: 10 wlv) using a Poltron PT3100 (speed setting 21,700rpm, 3 x 5 seconds) and centrifuged at 49,500 g for 30 minutes at 4°C. The supernatant was discarded and the pellet rehomogenised in 20 mM HEPES buffer, pH 7.5 containing 100 mM sodium chloride and 10 mM magnesium chloride (equivalent to 12.5 mg wet weight of tissue/mi). Membranes were stored at-80°C until required.

Membranes were thawed, diluted 1: 10 in ice-cold 20 mM HEPES buffer, pH 7.5 containing 100 mM sodium chloride and 10 mM magnesium chloride and homogenised using a Poltron PT3100 as above. Diluted membranes (200 ut ; equivalent to 0.25 mg wet weight of tissue/tube) were incubated with 200 ut of 20 mM HEPES buffer, pH 7.5 containing 100 mM sodium chloride and 10 mM magnesium chloride and 50 ul of [3H] N-methylscopolamine at a single concentration of 0.15 nM and 50 pi of distilled water (total binding) or 50 ut of test compound (at a single concentration of leM or at 10 concentrations ranging from 10-11- 10-3 M) or 50 ut of atropine sulphate (1 uM ; non-specific binding) for 30 min at 30°C.

Membrane bound radioactivity was recovered by filtration under vacuum through Skatron 11734 filters using a Skatron cell harvester. Filters were rapidly washed with ice-cold 20 mM HEPES buffer, pH 7.5 (wash 1, 2 at setting 5,5). The scored filter paper discs were punched out into vials, scintillation fluid added and radioactivity determined by liquid scintillation counting.

For each of these tests measuring the ability of compounds of Formula f to displace standard ligands from 5-HT1A receptors and 5-hydroxytryptamine (5-HT) and noradrenaline (NA) reuptake sites and muscarinic receptors in vitro, the percentage displacement of specific binding of tritiated ligand by 10-6 M test compound was calculated in the following way.

Firstly, specific binding of tritiated ligand in the absence (A) and presence (B) of test compound was determined: In the absence of compound: A (dpm) = Total binding (dpm)-Non-specific binding (dpm) In the presence of compound (10-6M) : B (dpm) = Binding at 10-6M (dpm)-Non-specific binding (dpm) The specific binding of tritiated ligand in the presence (B) of compound was then converted to a percentage of specific binding of tritiated ligand in the absence (A) of compound: % Specific binding at 10-6M = B (dpm)/A (dpm) x 100 The percentage displacement of specific binding of tritiated ligand by the test compound (10-6M) was then obtained by subtraction of the percentage specific binding in the presence of compound from the percentage specific binding in the absence of compound, which is taken as the maximum binding and so equals 100%: % Displacement at 1 0-6M = 100-% Specific binding at 1 o-6 M.

In some cases, displacement curves were then produced for compounds which displaced >50% of specific binding of the tritiated ligand at 10-6M using a range of concentrations of the compound. The Kj was then calculated by simultaneous fitting using equations derived from the Feldman equations by robust non-linear regression to data from three experiments simultaneously (De Lean et al., 1978; Munson and Rodbard, 1980; Feldman, 1992).

Munson PJ and Rodbard D. Ligand: a versatile computerised approach for characterisation of ligand binding systems. Anal Biochem 1980 ; 107: 220.

Feldman HA. Mathematical theory of complex ligand binding systems at equilibrium : some methods for parameter fitting. Anal Biochem 1992: 48,317.

De Lean A, Munson PJ and Rodbard D. Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose- response curves. Am J Physiol 1978: 235 (2), E97-E102.

The results obtained in the above tests for 5-HT1A binding and 5-HT and NA uptake and muscarinic binding for the final products of Examples 1 to 3 hereinafter are given in Table 1 below. Kjs are in nM. % Figures are for % displacement at 10- 6 M for a single determination.

TABLE 1 Example No. 5-HT1A 5-HT uptake NA uptake Muscarinic 1 28 18% 5. 8 5% 2 94% 12% 96% 5% 3 52 88% 7. 7 3% Compounds of the present invention show reduced affinity for muscarinic receptors compared to Example 3 of W097/02269 which has a K ; of 57nM Muscarinic affinity may cause undesired side-effects, for example dry mouth, blurred vision, sweating, palpitations, constipation and aggravation of narrow angle glaucoma (Blackwell, B. Adverse effects of antidepressant drugs. Part 1 Monoamine

oxidase inhibitors and tricyclics. Drugs 21,202-219,1981). Obviously it is desirable for compounds to have minimal affinity for muscarinic receptors.

The ability of compounds of the invention to inhibit monoamine oxidase A activity is demonstrable by the following test.

The assay was performed using the following general procedure in which the tissue source was human placenta : Enzyme Substrate Incubation Reaction Method of detection product MAO-A (h) Kynuramine 30min/30°C 4-OHquinoline Spectrophotometry (0.15mM) The compounds were tested at 1 and 10micromolar in duplicate.

Ref. Weyler, W. and Salach, J. I. (1985) Purification and properties of mitochondrial monoamine oxidase type A from human placenta. J. Biof : Chem., 260: 13199- 13207.

Especially preferred compounds of the present invention may have significantly reduced MAOA inhibitory activity compared to compounds exemplified in W097/02269.

The combination of inhibition of monoamine oxidase activity and 5-HT reuptake inhibition may cause serotonin syndrome (Stembach, H. Serotonin syndrome. Am. J. Psychiatry 148,705-713,1991) which is highly undesirable.

Especially preferred compounds of the present invention also exhibit higher 5-HT1A affinity andlor greater selectivity over muscarinic activity compared to compounds of the prior art.

Acute feeding studies Animals and environment Experiments were performed on male Sprague-Dawley rats (300-450 g at the start of the experiment) which were obtained from Charles River (Margate). Animals were individually-housed in polypropylene cages with metal grid floors at a temperature of 21i1 °G and 55% humidity. Polypropylene trays were placed below each cage. Animals were maintained on a reverse phase light-dark cycle. Lights were off from 09.30 h to 17.30 h during which time the room was illuminated by red light. Animals had free access to a powdered rat diet and tap water at all times. The diet was contained in glass feeding jars (10 cm diameter; 8 cm deep) with aluminium lids. Each lid had a hole (3 cm diameter) cut in it to allow access to the food.

Animals were accustomed to these conditions for at least two weeks before experimentation.

Test procedure On the day prior to testing, the animals were randomly allocated to treatment groups containing 6-8 rats, weighed and their food intakes over a 6 h period were measured. These baseline readings were taken to ensure that the body weights and. food intakes of the different groups of rats were not significantly different before drug treatment. On the test day, animals were given vehicle or one of three doses of the test drug. All drugs were dosed orally at the onset of the dark phase since rats consume most of their food during this period. Feeding jars were weighed (to the nearest 0. 1g) at the time of drug administration and 1, 2,4,6 and 24 h after dosing.

At each reading, the trays below the cages were examined for spiltfood which was then returned to the feeding jar. However, spillage of food from the feeding jars was generally negligible.

All drug doses are expressed as the free base. Drugs were dissolved in deionised water or suspended in 0.4% cellosize using a sonic bath.

Data analysis Variations in body weight were accounted for by expressing the results as g/kg rat weight (treatment group means s. e. mean). EDso values (the dose of a drug required to reduce food intake to 50% of the control values) were calculated from a logistic sigmoid curve using a dedicated computer program. Statistical comparisons between mean group intakes were made using analysis of variance and Dunnett's test (two-tailed).

Especially preferred compounds of the present invention have superior activity in acute feeding studies compared to compounds exemplified in W097/02269.

The compounds of the present invention are particularly useful in treating obesity and related co-morbid conditions, for example, diabetes, hyperglycaemia and hyperlipidaemia.

It is known that monoamine reuptake inhibitors which are used to treat obesity are often associated with cardiovascular side effects, for example, increased heart rate and increased blood pressure. The compounds of the present invention reduce the cardiovascular side effects which might be expected to occur from the administration of a monoamine reuptake inhibitor particularly a noradrenaline reuptake inhibitor. Whilst not wishing to be bound by theory it is likely that the combination of 5-HT1A agonism in the compounds of the present invention reduces the cardiovascular side effects which might have arisen from their monoamine reuptake inhibition particularly their noradrenaline reuptake inhibition.

The beneficial properties of especially preferred compounds of the present invention in reducing cardiovascular side-effects can be demonstrated in rat telemetry studies in which heart rate, blood pressure, body temperature and locomotor activity are recorded continuously over time. Suitable methods are described in :

Brockway, BP, Mills, PA & Azar, SH (1991) A new method for continuous chronic measurement of blood pressure, heart rate and activity in the rat via radio-telemetry.

Clinical and Experimental Hypertension-Theory and Practice A13 (5), 885-895 and Guiol, C, Ledoussal, C & Surge, J-M (1992) A radiotelemetry system for chronic measurement of blood pressure and heart rate in the unrestrained rat. Validation of method. Journal of Pharmacological and Toxicological Methods 28,99-105.

The 5-HT1Sv agonism of especially preferred compounds of the present invention can be determined by electrophysiology by methods known to those skilled in the art.

The invention is illustrated by the following Examples which are given by way of example only. The final product of each of these Examples was characterised by one or more of the following procedures : high performance liquid chromatography; elemental analysis, nuclear magnetic resonance spectroscopy, mass spectroscopy and infrared spectroscopy.

Examples Example 1 A mixture of 2-bromophenol (206 g), bromoacetaldehyde dimethyl acetal (202 g), potassium carbonate (500 g) and dimethylformamide (1000 ml) was stirred under nitrogen at 95 °C for 20 hours then cooled to ambient temperature and poured into water (1000 mi). The product was extracted into ether (3 x 500 ml), the combined extracts were dried (MgS04) and the solvent removed in vacuo to give 2- (2- bromophenoxy) acetaldehyde dimethyl acetal (273 g) as å gum which was used without further purification.

A mixture of 2- (2-bromophenoxy) acetaldehyde dimethyl acetal (273 g), phosphoric acid (85 wt. % solution in water, 257 mi), phosphorus pentoxide (77 g) and chlorobenzene (2000 mi) was heated at 95 °C for 3 days then allowed to cool to ambient temperature and poured onto ice-water (2000 ml). The resulting solid was removed by filtration and the product extracted from the filtrate into dichloromethane (3 x 500 mi). The combined extracts were washed with water (2 x 500 ml), then dried (MgS04) and concentrated in vacuo. The residue was purified by distillation in vacuo to give 7-bromobenzolb] furan (133 g) as a colourless oil, b. p. 60-65 °C @ 0.6 mmHg.

A solution of 7-bromobenzo [b] furan (34.0 g) in tetrahydrofuran (340 mi) was added over 15 minutes under nitrogen to a stirred mixture of magnesium turnings (4.35 g) and a crystal of iodine. The mixture was stirred at ambient temperature for 1 hour, then a solution of N-methoxy-N-methylpropionamide (22. 1 g) in tetrahydrofuran (60 ml) was added. The mixture was heated under reflux for 2 hours, then it was cooled to ambient temperature and quenched by the addition of 2M hydrochloric acid (170 mi). The majority of the tetrahydrofuran was removed in vacuo, then the residue was diluted with water (500 mi) and the product extracted into ethyl acetate (600 ml). The extract was washed with water (2 x 500mi) and saturated aqueous sodium chloride solution (500 ml), dried (Na2S04), and the solvents were removed vacuo. The residue was purified by flash chromatography over silica using 99: 1 followed by 97: 3 mixtures of petroleum ether (b. p. 40-60 °C) and ethyl acetate as eluants. Appropriate fractions were combined and the solvents removed// vacuo to

give 1-(benzotbJfuran-7-yl) propan-1-one (19.37 g) as an off-white solid, m. p. 49- 51°C.

Phenyltrimethylammonium tribromide (4. 3 g) was added in portions under nitrogen at 0 °C over 1 minute to a stirred solution of 1-(benzo [b] furan-7-yl) propan-1- one (1.99 g ; prepared in a manner similar to that described above) intetrahydrofuran (25 ml), the mixture was stirred for 30 minutes at 0°C, then at ambient temperature for 3 hours, then it was filtered and the solvent was removed in vacuo. The residue was dissolved in ethanol (40 mi), acetic acid (20 ml) and 2-imidazolidinethione (1.16 g) were added, and the mixture was heated under reflux for 20 hours. The solvents were removed in vacuo, the residue was triturated with ethanol (30 ml) for 1 hour and the resulting solid was collected by filtration, washed with ethanol (25-ml) and dried in vacuo at 70 °C to give 3-(benzo [bafuran-7-yl)-2-methyl-5, 6- dihydroimidazo [2,1-b] thiazole hydrobromide (2.0 g) as a colourless solid, m. p. 255- 257 °C.

Example 2 Aqueous sodium hydroxide solution (5M, 38 ml) was added to a stirred mixture of dichloromethane (500 ml), water (1250 mi) and 3- (benzo [b] furan-7-yl)-2- methyl-5, 6-dihydroimidazo [2,1-b] thiazole hydrobromide (29.07 g; prepared in a manner similar to that described in Example 1). The mixture was stirred for 30 minutes then the dichloromethane layer was separated and the aqueous phase extracted with dichloromethane (2 x 500 ml). The combined dichloromethane extracts were dried (MgS04), and the solvents were removed in vacuo to give 3- (benzo [b] furan-7-yi)-2-methyl-5, 6-dihydroimidazo [2,1-bjthiazole as a solid (22.08 g).

Concentrated hydrochloric acid (7.8 mi) was added to a solution of 3-(benzo[b]furan- 7-yl)-2-methyl-5, 6-dihydroimidazo [2,1-b] thiazole (21.0 g) in ethanol (190 ml), then the mixture was added dropwise over 5 minutes with stirring to ether (1100 ml). The resulting suspension was stirred for 30 minutes, then the product was collected by filtration, washed with ether (400 ml) and dried in vacuo at 60 °C to give 3- (benzolbJfuran-7-yl)-2-methyl-S, 6-dihydroimidazo [2,1-bithiazole hydrochloride (24.7 g) as a colourless solid, m. p. 273-275 °C.

Example 3 Trimethylsilyl cyanide (5.0 g), then boron trifluoride etherate (8 drops) were added with stirring under nitrogen to 6,7-dihydro-4 (5benzofuranone (6.1 g). The mixture was stirred at ambient temperature for 2 hours, at 60°C for 40 minutes and at 100 °C for 5 minutes then it was allowed to cool to ambient temperature. Pyridine (34 ml), then phosphorous oxychloride (6.6 mi) were added, then the mixture was heated to 125 °C for 1. 75 hours whilst volatile materials were removed by distillation.

The residual material was allowed to cool to ambient temperature then poured onto ice (150 mil). Ether (50 mi) was added then the mixture was filtered through Celite.

The Celite was washed with water (3 x 100 m !) and ether (3 x 75 ml), then the combined aqueous layers were extracted with ether (2 x 100 ml). The combined ether layers were washed with 5M hydrochloric acid (100 ml), water (100 ml) and saturated aqueous sodium chloride solution (100 ml), then they were dried (MgSO4) and solvents were removed in vacuo to give 6,7-dihydrobenzo [b] furan-4-carbonitrile (1.3. g) as a brown gum which was used without further purification.

A mixture of 6, 7-dihydrobenzo[b]furan-4-carbonitrile (1.3 g), 2,3-dichloro-5,6- dicyano-1, 4-benzoquihone (2.04 g) and toluene (10 mi) was stirred and heated at 80 °C for 45 minutes, allowed to stand at ambient temperature for 20 hours, then heated at 80 °C for 1.25 hours. The mixture was cooled to ambient temperature then insoluble materials were removed by filtration. The filter cake was washed with toluene (3 x 20 mi) and the solvents removed from the combined filtratesin vacuo to give a residue which was purified by flash chromatography over silica using a 19: 1 mixture of petroleum ether (b. p. 40-60 °C) and ethyl acetate as eluant. Appropriate fractions were combined and the solvents removed in vacuo to give benzo [b] furan-4- carbonitrile as a yellow solid (0.22 g), m. p. 46-48 °C.

A solution of benzo [b] furan4-carbonitrile (0.33 g ; prepared in a manner similar to that described above) in ether (5 mi) was added over 1 minute under nitrogen to a stirred solution of ethylmagnesium bromide (2M solution in tetrahydrofuran; 2.2 ml). The mixture was stirred at ambient temperature for 2.25 hours, heated at 30-40 °C for 1 hour, then allowed to cool to ambient temperature and poured onto ice (7 ml). 5M Hydrochloric acid (3 mi) was added and the mixture was washed with ether (10 ml). The aqueous layer was heated at 95 °C for 30 minutes, then allowed to cool to ambient temperature. The product was extracted

into ether (2 x 20 ml) then the extracts were combined, washed with water (15 ml) and saturated aqueous sodium chloride solution (15 ml), dried (MgSO4) and solvents removed in vacuo to give 1-(benzo [b] furan-4-yl) propan-1-one (0.14 g) as a yellow gum which was used without further purification.

Phenyltrimethylammonium tribromide (0.30 g) was added to a stirred solution of 1-tbenzo [b3furan-4-yl) propan-1-one (0.14 g) in tetrahydrofuran (4 ml), the mixture was stirred for 23 hours at ambient temperature, then resulting solids were removed by filtration. The filter cake was washed with dichloromethane (10 ml), then the combined filtrates were washed with water (30 ml). The separated water layer was extracted with dichloromethane (10 mf), then the combined organic extracts were dried (MgS04) and the solvents were removed in vacuo. A mixture of the residue (0.27 g), 2-imidazolidinethione (66 mg) and ethanol (3 ml) was heated under reflux for 20 minutes. Acetic acid (1.5 ml) was added, the mixture was heated under reflux for 21.5 hours, then it was allowed to cool to ambient temperature. The solvents were removed in vacuo to give a residue which was purified by flash chromatography over silica using 19: 1 followed by 9: 1 mixtures of dichloromethane and methanol as eluants. Appropriate fractions were combined and the solvents removed in vacuo to give 3-(benzo[b]furan-4-yl)-2-methyl-5, 6-dihydroimidazo [2, 1- b jthiazole hydrobromide (0.12 g) as an off-white solid, m. p. 166-168 °C.

Pharmaceutical Examples Example A The use of compounds of the present invention in the manufacture of pharmaceuticai compositions is illustrated by the following description. In this description the term"active compound"denotes any compound of the invention but particularly any compound which is the final product of one of the preceding Examples. a) Capsules In the preparation of capsules, 10 parts by weight of active compound and 240 parts by weight of lactose are de-aggregated and blended. The mixture is filled into hard gelatin capsules, each capsule containing a unit dose or part of a unit dose of active compound. b) Tablets Tablets are prepared from the following ingredients.

Parts by weight Active compound 10 Lactose 190 Maize starch 22 Polyvinylpyrrolidone 10 Magnesium stearate 3 The active compound, the lactose and some of the starch are de-aggregated, blended and the resulting mixture is granulated with a solution of the polyvinyl- pyrrolidone in ethanol. The dry granulate is blended with the magnesium stearate and the rest of the starch. The mixture is then compressed in atabletting machine to give tablets each containing a unit dose or a part of a unit dose of active compound.

c) Enteric coated tablets Tablets are prepared by the method described in (b) above. The tablets are 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 active compound is incorporated in 1300 parts by weight of triglyceride suppository base and the mixture formed into suppositories each containing a therapeutically effective amount of active ingredient.