Piperidine and azetidine derivatives as GlyT1 inhibitors

1. A method for treating a subject suffering from schizophrenia which comprises administering to the subject in need thereof a therapeutically effective amount of a compound of the formula I:

wherein:

both p's are either 1 or 2 to form an azetidine or a piperidine ring:

R 1 is C 3-6 cycloalkyl, cyclopropylmethyl or heterocycle where the heterocycle is a five-membered unsaturated ring containing 1, 2, 3 or 4 heteroatoms chosen from O, N or S, at most one heteroatom being O or S, or a six-membered unsaturated ring containing 1, 2 or 3 nitrogen atoms, R 1 being optionally substituted by halogen or hydroxyl;

R 2 is selected from:

(1) phenyl, which is substituted with R 2a , R 2b and R 2c ,

(2) heterocycle, which is substituted with R 2a , R 2b and R 2c ,

(3) C 1-8 alkyl, which is unsubstituted or substituted with 1-6 halogen, hydroxy, —NR 10 R 11 , phenyl or heterocycle, where the phenyl or heterocycle is substituted with R 2a , R 2b and R 2c , and where R 10 and R 11 are independently selected from:

 (a) hydrogen,

 (b) —C 1-6 alkyl, which is unsubstituted or substituted with hydroxy, 1-6 fluoro or —NR 12 R 13 , where R 12 and R 13 are independently selected from hydrogen and —C 1-6 alkyl,

 (c) —C 3-6 cycloalkyl, which is unsubstituted or substituted with hydroxy, 1-6 fluoro or —NR 12 R 13 ,

 (d) benzyl, and

 (e) phenyl,

(4) C 3-6- 6cycloalkyl, which is unsubstituted or substituted with 1-6 halogen, hydroxy or —NR 10 R 11 , and

(5) —C 1-6 alkyl-(C 3-6 cycloalkyl), which is unsubstituted or substituted with 1-6 halogen, hydroxy or —NR 10 R 11 ;

R 2a , R 2b and R 2c are independently selected from:

(1) hydrogen,

(2) halogen,

(3) —C 1-6 alkyl, which is unsubstituted or substituted with:

 (a) 1-6 halogen,

 (b) phenyl,

 (c) C 3-6 cycloalkyl, or

 (d) —NR 10 R 11 ,

(4) —O—C 1-6 alkyl, which is unsubstituted or substituted with 1-6 halogen,

(5) hydroxy,

(6) —SCF 3 ,

(7) —SCHF 2 ,

(8) —SCH 3 ,

(9) —CO 2 R 9 , wherein R 9 is independently selected from:

 (a) hydrogen,

 (b) —C 1-6 alkyl, which is unsubstituted or substituted with 1-6 fluoro,

 (c) benzyl, and

 (d) phenyl,

(10) —CN,

(11) —SO 2 R 9 ,

(12) —SO 2 -NR 10 R 11 ,

(13) —NR 10 R 11 ,

(14) —CONR 10 R 11 , and

(15) —NO 2 ;

R 3 is a heterocycle, which is substituted with R 2a , R 2b and R 2c ;

R 4 and R 5 are independently selected from:

(1) hydrogen, and

(2) C 1-6 alkyl, which is unsubstituted or substituted with halogen or hydroxyl,

or R 4 and R 5 taken together form a C 3-6 cycloalkyl ring:

A is selected from:

(1) —O—, and

(2) —NR 10 ;

m is zero or one, whereby when m is zero, R 2 is attached directly to the carbonyl;

or a pharmaceutically acceptable salt thereof.

2. A method for treating a subject suffering from schizophrenia which comprises administering to the subject in need thereof a therapeutically effective amount of a compound which is selected from the group consisting of:

2,4-dichloro-N-{[4-(cyclopropylmethyl)-1-[(1-methyl-1H-pyrazol-4-yl)sulfonyl]piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-[4-(cyclopropylmethyl)-1-(1-methyl-1H- [1,2,3]-triazole-4-sulfonyl) piperidin-4-ylmethyl]-benzamide;

2,4-dichloro-N-[1-(1-methyl-1H-pyrazole-4-sulfonyl)-4-pyridin-2-ylmethyl-piperidin-4-ylmethyl]-benzamide;

2,4-dichloro-N-{[4-(3-fluoropyridin-2-yl)-1-[(1H-1,2,3-triazol-4-yl)sulfonyl]piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{[4-(3-fluoropyridin-2-yl)-1-[(1-methyl-1H-1,2,3-triazol-4-yl) sulfonyl]piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{[3-(3-fluoropyridin-2-yl)-1-(2-thienylsulfonyl)azetidin-3-yl]methyl}benzamide;

2,4-dichloro-N-{[3-(cyclopropylmethyl)-1-(1H-1,2,3-triazol-4-ylsulfonyl)azetidin-3-yl]methyl}benzamide;

2,4-dichloro-N-({3-(cyclopropylmethyl)-1-[(1-methyl-1H-1,2,3-triazol-4-yl)sulfonyl]azetidin-3-yl}methyl)benzamide;

or a pharmaceutically acceptable salt thereof.