Azetidine derivatives as FAAH inhibitors

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof:

wherein

Ar 1 is optionally substituted phenyl;

Ar 2 is optionally substituted phenyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl; and

Ar 3 is a divalent radical selected from the group consisting of optionally substituted phenylene and optionally substituted pyridinylene;

wherein the term “optionally substituted” means substituted with at least one substituent selected from (C 1 -C 6 )alkyl, (C 1 -C 6 )fluoroalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )fluoroalkoxy, (C 1 -C 6 )alkoxy-(C 1 -C 6 )alkyl, benzyloxy-(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy-(C 1 -C 6 )alkoxy, benzyloxy-(C 1 -C 6 )alkoxy, hydroxy, hydroxy(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkoxy, mercapto, mercapto(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylthio, cyclopropyl, halo, nitro, nitrile, —COOH, tetrazolyl, —COOR A , —COR A , —SO 2 R A , —CONH 2 , —SO 2 NH 2 , —CONHR A , —SO 2 NHR A , —CONR A R B , —SO 2 NR A R B , —NH 2 , —NHR A , —NR A R B , —OCONH 2 , —OCONHR A , —OCONR A R B , —NHCOR A , —NHCOOR A , —NR B COOR A , —NHSO 2 OR A , —NR B SO 2 OR A , —NHCONH 2 , —NR A CONH 2 , —NHCONHR B , —NR A CONHR B , —NHCONR A R B , or —NR A CONR A R B wherein R A and R B are independently a (C 1 -C 4 )alkyl group, or R A and R B when attached to the same nitrogen may form, together with that nitrogen, a cyclic amino group.

2. A compound as claimed in claim 1 wherein Ar 2 is 3-pyridyl, pyrimidin-4-yl, pyrazin-2-yl or pyridazin-3-yl, any of which being optionally substituted.

3. A compound as claimed in claim 1 wherein Ar 3 is an optionally substituted divalent 1,4-phenylene or a 2,5-pyridinylene radical of formula:

wherein the bond marked with a single asterisk is attached to Ar 1 and the bond marked with a double asterisk is attached to the oxygen.

4. A compound as claimed in claim 1 wherein any optional substituents in Ar 1 , Ar 2 and Ar 3 are independently selected from chloro, fluoro, bromo, cyclopropyl, methyl, mono-, di- or tri-methyl, trifluoromethyl, difluoromethyl, monofluoromethyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, 2-methoxyethoxy, 2-benzyloxy-ethoxy, 2-hydroxy-ethoxy, mono-, di- or tri-fluoromethoxy, cyano, hydroxyl; —CO 2 R 1 and —SO 2 R 1 wherein R 1 is hydrogen, methyl or ethyl; tetrazolyl; —NR 2 R 3 , —CH 2 NR 2 R 3 and —C(═O)NR 2 R 3 wherein R 2 and R 3 are independently hydrogen, methyl or ethyl.

5. A compound as claimed in claim 1 wherein:

Ar 2 is 3-pyridyl, pyrimidin-4-yl, pyrazin-2-yl or pyridazin-3-yl;

Ar a is an optionally substituted divalent 1,4-phenylene or a 2,5-pyridinylene radical of formula:

wherein the bond marked with a single asterisk is attached to Ar 1 and the bond marked with a double asterisk is attached to the oxygen; and

Ar 1 is optionally substituted phenyl.

6. A compound as claimed in claim 5 wherein Ar 1 is phenyl, 2-fluorophenyl, 3-(2-methoxy-ethoxy)-phenyl, or 2-methoxy-5-(2-methoxy-ethoxy)-phenyl.

7. A compound as claimed in claim 5 wherein Ar 2 is pyridazin-3-yl.

8. A pharmaceutical composition comprising a compound as claimed in claim 1 , together with one or more pharmaceutically acceptable carriers and/or excipients.

9. A method of treatment of a disease or medical condition which benefits from inhibition of FAAH activity, wherein the disease or condition is anxiety, depression, pain, inflammation, pruripus, a sleep disorder or a movement disorder, comprising administering to a subject suffering such disease or condition an effective amount of a compound as claimed in claim 1 .

10. A compound as claimed in claim 1 selected from the group consisting of:

3-(biphenyl-4-yloxy)-azetidine-1-carboxylic acid phenylamide;

3-(Biphenyl-4-yloxy)-azetidine-1-carboxylic acid (3-fluoro-phenyl)-amide;

3-(Biphenyl-4-yloxy)-azetidine-1-carboxylic acid (2-fluoro-phenyl)-amide;

3-(Biphenyl-4-yloxy)-azetidine-1-carboxylic acid pyridin-3-ylamide;

3-{5-[3-(2-Methoxy-ethoxy)-phenyl]-pyridin-2-yloxy}-azetidine-1-carboxylic acid pyrimidin-4-ylamide;

3-{5-[3-(2-Methoxy-ethoxy)-phenyl]-pyridin-2-yloxy}-azetidine-1-carboxylic acid pyrazin-2-ylamide;

3-{5-[3-(2-Methoxy-ethoxy)-phenyl]-pyridin-2-yloxy}-azetidine-1-carboxylic acid pyridazin-3-ylamide;

3-{5-[3-(2-Methoxy-ethoxy)-phenyl]-pyridin-2-yloxy}-azetidine-1-carboxylic acid pyridin-3-ylamide;

3-{5-[3-(2-Benzyloxy-ethoxy)-phenyl]-pyridin-2-yloxy}-azetidine-1-carboxylic acid pyridazin-3-ylamide;

3-{5-[3-(2-Hydroxy-ethoxy)-phenyl]-pyridin-2-yloxy}-azetidine-1-carboxylic acid pyridazin-3-ylamide;

3-{5-[2-Methoxy-5-(2-methoxy-ethoxy)-phenyl]-pyridin-2-yloxy}-azetidine-1-carboxylic acid pyridazin-3-ylamide;

3-[5-(2,5-Dimethoxy-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid pyridazin-3-ylamide;

3-(5-Phenyl-pyridin-2-yloxy)-azetidine-1-carboxylic acid pyridazin-3-ylamide;

3-[5-(2,6-Difluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid pyridazin-3-ylamide;

1-(3-{5-[2-Chloro-5-(2-methoxy-ethoxy)-phenyl]-pyridin-2-yloxy}-azetidin-1-yl)-2-pyridazin-3-yl-ethanone;

3-[5-(2-Fluoro-phenyl]-pyridin-2-yloxy}-azetidine-1-carboxylic acid pyrazin-2-ylamide;

3-[5-(2-Methoxy-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid pyridazin-3-ylamine;

3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid pyridazin-3-ylamide;

3-[5-(2-Fluoro-3-methoxy-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid pyridazin-3-ylamide;

3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (6-methyl-pyridazin-3-yl)-amide;

3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (6-methoxy-pyridazin-3-yl)-amide;

3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (5-methyl-[1,3,4]oxadiazol-2-yl)-amide;

3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid pyridazin-4-ylamide;

3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (5-methyl-pyridazin-3-yl)-amide; and

3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (4-methyl-pyridazin-3-yl)-amide.