N-aroyl cyclic amine derivatives as orexin receptor antagonists

1. A compound of formula (I):

wherein

X represents CH 2 ;

Y represents CH 2 , CH(OH), or CH 2 CH(OH);

Het is an optionally substituted benzofuranyl;

Ar 2 represents an optionally substituted pyrazolyl group, wherein the pyrazolyl group is substituted by R 1 and further optional substituents;

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

wherein said optionally substituted Het, Ar 2 , and R 1 groups are 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 1-4 )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, or 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 , R a SO 2 NR b (CH 2 ) r , R a R b N(CH 2 ) n —, R a R b N(CH 2 ) n O—, wherein r represents zero or an integer from 1 to 4, n represents an integer from 1 to 4, and 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 optionally substituted phenyl.

3. A compound according to claim 1 wherein Ar 2 is optionally substituted by (C 1-4 )alkyl, hydroxy(C 1-4 )alkyl, R a R b N, (C 1-4 )alkoxy, R a R b N(CH 2 ) n , (C 1-4 )acyl, and (C 1-4 )alkylamido.

4. A compound according to claim 1 wherein Y represents CH 2 .

5. A compound:

(RS)-1-(2-Benzofuran-2-ylmethyl-piperidin-1-yl)-1-[4-(4-fluoro-phenyl)-1-methyl-1-H-pyrazol-3-yl]-methane;

(RS)-1-(2-Benzofuran-2-ylmethyl-piperidin-1-yl)-1-[4-(4-fluoro-phenyl)-1H-pyrazol-3-yl]-methanone;

(RS)-2-(1-{1-[4-(4-Fluorophenyl)-1-methyl-1H-pyrazol-3-yl]-methanoyl}-piperidin-2-ylmethyl)-benzofuran-3-carboxylic acid amide;

(RS)-1-[2-(4-Fluoro-benzofuran-2-ylmethyl)-piperidin-1-yl]-1-[4-(4-fluoro-phenyl)-1-methyl-1H-pyrazol-3-yl]-methanone;

or a pharmaceutically acceptable salt of any one thereof.

6. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

7. 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 according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein said disease or disorder is selected from obesity and obesity associated with Type II diabetes.

8. A method of treating insomnia which comprises administering to a subject in need thereof an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.