Piperidine compounds for use as orexin receptor antagoinst

1. A compound of formula (I):

wherein:

X is (CH 2 ),

Y is CH 2 , CHOH, or —CH 2 CH(OH)—;

Het is an optionally substituted 1,3,4-oxadiazolyl substituted by R 2 , wherein R 2 is an optionally substituted aryl;

Ar 2 is an optionally substituted thiazolyl, pyrazolyl, thienyl, benzofuranyl, or triazolyl, wherein said thiazolyl, pyrazolyl, thienyl, benzofuranyl, or triazolyl is substituted by R 1 and is further optionally substituted;

R 1 is hydrogen, an optionally substituted (C 1-4 )alkoxy, halo, cyano, optionally substituted(C 1-6 )alkyl, or optionally substituted phenyl;

wherein said optionally substituted oxadiazolyl, aryl, thiazolyl, pyrazolyl, thienyl, benzofuranyl, triazolyl, (C 1-4 )alkoxy, (C 1-6 )alkyl, or phenyl is optionally substituted by halogen, hydroxy, oxo, cyano, nitro, (C 1-4 )alkyl, (C 1-4 )alkoxy, hydroxy(C 1-4 )alkyl, hydroxy(C 1-4 )alkoxy, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, aryl(C 1-4 )alkoxy, (C 1-4 )alkylthio, hydroxy(C 1-4 )alkyl, (C 1-4 )alkoxy(C 1-4 )alkyl, (C 3-6 )cycloalkyl(C 1-4 )alkoxy, (C 1-4 )alkanoyl, (C 1-4 )alkoxycarbonyl, (C 1-4 )alkylsulfonyl, (C 1-4 )alkylsulfonyloxy, (C 1-4 )alkylsulfonyl(C 1-4 )alkyl, arylsulfonyl, arylsulfonyloxy, arylsulfonyl(C 1-4 )alkyl, (C 1-4 )alkylsulfonamido, (C 1-4 )alkylamido, (C 1-4 )alkylsulfonamido(C 1-4 )alkyl, (C 1-4 )alkylamido(C 14 )alkyl, arylsulfonamido, arylcarboxamido, arylsulfonamido(C 1-4 )alkyl, arylcarboxamido(C 1-4 )alkyl, aroyl, aroyl(C 1-4 )alkyl, aryl(C 1-4 )alkanoyl, (C 1-4 ) acyl, aryl, aryl(C 1-4 )alkyl, (C 1-4 )alkylamino(C 1-4 )alkyl, R a R b N—, R a OCO(CH 2 ) r , R a CON(R a )(CH 2 ) r , R a R b NCO(CH 2 ) r , R a R b NSO 2 (CH 2 ) r or R a SO 2 NR b (CH 2 ) r , wherein r represents zero or an integer from 1 to 4, or R a R b N(CH 2 )n- or R a R b N(CH 2 )nO—, wherein n represents an integer from 1 to 4, wherein each of R a and R b independently represents a hydrogen atom or a (C 1-4 )alkyl group;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 wherein R 1 represents an optionally substituted phenyl group.

3. A compound according to claim 1 wherein Y is CH 2 .

4. A compound according to claim 1 wherein optional substituents for said optionally substituted (C 1-4 )alkoxy, (C 1-6 )alkyl or phenyl of R 1 are halogen, (C 1-4 )alkoxy(C 1-4 )alkyl, R a R b N, R a R b N(CH 2 )n, R a R b N(CH 2 )nO, (C 1-4 )alkoxy, (C 1-4 )alkanoyl and (C 1-4 )alkyl.

5. A compound of formula (I) according to claim 1 selected from:

(RS)-1-[5-(4-Fluoro-phenyl)-2-methyl-thiazol-4-yl]-1-[2-(5-phenyl-[1,3,4]oxadiazol-2-ylmethyl)-piperidin-1-yl]-methanone;

(RS)-1-[5-(4-Fluoro-phenyl)-2-methyl-2H-[1,2,3]triazol-4-yl]-1-[2-(5-phenyl-[1,3,4]oxadiazol-2-ylmethyl)-piperidin-1-yl]-methanone;

(RS)-1-{2-[5-(2,5-Dimethyl-2H-pyrazol-3-yl)-[1,3,4]oxadiazol-2-ylmethyl]-piperidin-1-yl}-1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone;

(RS)-1-[2-(5-Benzofuran-2-yl-[1,3,4]oxadiazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone;

and a pharmaceutically acceptable salt thereof.

6. A compound according to claim 1 , having the formula:

wherein Ar 2 and R 2 are selected from:

Ar 2

R 2

and a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition comprising the compound of formula (I), or the pharmaceutically acceptable salt thereof, according to claim 1 , and a pharmaceutically acceptable carrier.

8. A compound which is (RS)-1-Dibenzofuran-4-yl-1-{2-[5-(3-fluoro-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-piperidin-1-yl}-methanone or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof according to claim 8 , and a pharmaceutically acceptable carrier.

10. A method of treating a disease or disorder where an antagonist of a human orexin receptor is required, which comprises administering to a subject in need thereof an effective amount of the compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein said disease or disorder is selected from insomnia, parasomnia and jet-lag syndrome.

11. A method of treating a disease or disorder where an antagonist of a human orexin receptor is required, which comprises administering to a subject in need thereof an effective amount of the compound, or the pharmaceutically acceptable salt thereof, according to claim 8 , wherein said disease or disorder is selected from insomnia, parasomnia and jet-lag syndrome.

12. A method according to claim 10 , wherein said disease or disorder is insomnia.

13. A method according to claim 11 , wherein said disease or disorder is insomnia.

14. A method of treating a disease or disorder where an antagonist of a human orexin receptor is required, which comprises administering to a subject in need thereof an effective amount of the compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein said disease or disorder is selected from obesity and obesity associated with Type II diabetes.

15. A method of treating a disease or disorder where an antagonist of a human orexin receptor is required, which comprises administering to a subject in need thereof an effective amount of the compound, or the pharmaceutically acceptable salt thereof, according to claim 8 , wherein said disease or disorder is selected from obesity and obesity associated with Type II diabetes.