Granted Patent B2

US 7,825,135 · App. 10/593,950 · Granted Nov 2, 2010

Abstract

Claims (109)

1. A compound of formula Ic:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from the group consisting of:

(1) hydrogen,

(2) C 1-3 alkyl,

(3) fluoro,

(4) —CF 3 ,

(5) -morpholinyl, and

(6) —O—C 1-3 alkyl;

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

R 2a , R 2b and R 2c are independently selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) —C 1-6 alkyl,

(4) —CF 3 ,

(5) —OCF 3 ,

(6) —OCHF 2 ,

(7) —SCF 3 ,

(8) —SCHF 2 , and

(9) —NH 2 ;

R 3 is C 1-6 alkyl, which is unsubstituted or substituted with 1-6 halogen, hydroxyl, —NR 10 R 11 , or heterocycle, which is substituted with R 2a , R 2b and R 2c ;

R 4 and R 5 are independently selected from the group consisting of:

(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; and

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, and where R 10 and R 11 may be joined to form an azetidinyl ring, (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.

2. The compound of Claim 1 wherein R 2a , R 2b and R 2c are independently selected from the group consisting of:

(1) hydrogen,

(2) fluoro,

(3) chloro,

(4) bromo,

(5) —CF 3 , and

(6) —NH 2 .

3. The compound of claim 1 wherein R 1 is hydrogen or methyl.

4. The compound of claim 1 wherein R 4 is C 1-3 alkyl and R 5 is hydrogen or C 1-3 alkyl.

5. The compound of claim 4 wherein R 4 is C 1-3 alkyl in the (S) configuration and R 5 is hydrogen.

6. The compound of claim 4 wherein R 4 is methyl and R 5 is hydrogen.

7. The compound of claim 1 wherein R 4 is methyl and R 5 is methyl.

8. The compound of claim 1 wherein R 4 is hydrogen and R 5 is hydrogen.

9. The compound of claim 1 wherein R 3 is selected from C 1-6 alkyl and C 1-6 alkyl-fluoro.

10. The compound of claim 9 wherein R 3 is —CH 2 CH 3 .

11. The compound of claim 9 wherein R 3 is —(CH 2 ) 2 CH 3 .

12. A compound which is selected from the group consisting of:

2-chloro-3,6-difluoro-N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{[4-(6-methylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{(1S)-1-[1 -(ethylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}benzamide;

2-chloro-3,6-difluoro-N-{1-methyl-1 -[1 -(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}benzamide;

2-chloro-N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamide;

2,6-dichloro-N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}-benzamide;

2-bromo-N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamide;

2-chloro-6-fluoro-N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamide;

2-amino-6-chloro-N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamide;

2-fluoro-6-methoxy-N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamide;

2-chloro-N-{[4-(6-methylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2-fluoro-N-{[4-(6-methylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}-6-trifluoromethyl)benzamide;

2,6-difluoro-N-{[4-(6-methylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2-chloro-6-fluoro-N-{[4-(6-methylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2,6-dichloro-N-{[4-(6-methylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2-chloro-3,6-difluoro-N-{[4-(6-methylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2-chloro-4-fluoro-N-{[4-(6-methylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

4-chloro-2-fluoro-N-{[4-(6-methylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{[4-(4-methylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide 2,4-dichloro-N-{[1-(methylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{[1-(isopropylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamide 2,4-dichloro-N-{[1-(ethylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamide;

2-chloro-6-fluoro-N-{[4-(6-morpholin-4-ylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{[4-(6-morpholin-4-ylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2,4,5-trifluoro-N-{[4-(6-methoxypyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2,4-dichloro-5-fluoro-N-{[4-(6-methoxypyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

N-{[1 -(ethylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}-2,4-difluorobenzamide;

2,4-dichloro-N-{1-methyl-1 -[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}benzamide;

2-chloro-3,6-difluoro-N-{1-methyl-1 -[1 -(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}benzamide;

N-{1-methyl-1 -[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}-2-(trifluoromethoxy)benzamide;

2,4-dichloro-N-{1-methyl-1 -[4-(6-methylpyridin-2-yl)-1 -(propylsulfonyl)piperidin-4-yl]ethyl}benzamide;

2-chloro-3,6-difluoro-N-{1-methyl-1 -[4-(6-methylpyridin-2-yl)-1 -(propylsulfonyl)piperidin-4-yl]ethyl}benzamide;

2,4-dichloro-N-{(1S)-1-[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}benzamide;

2-chloro-3,6-difluoro-N-{(1S)-1-[1 -(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}benzamide;

2,4-dichloro-N-{(1S)-1 -[4-(6-methylpyridin-2-yl)-1 -(propylsulfonyl)piperidin-4-yl]ethyl}benzamide;

2-chloro-3,6-difluoro-N-{(1S)-1-[4-(6-methylpyridin-2-yl)-1 -(propylsulfonyl)piperidin-4-yl]ethyl}benzamide;

2-chloro-N-{(1S)-1-[1 -(ethylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}benzamide;

2-chloro-N-{(1S)-1-[1 -(ethylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}-3 ,6-difluorobenzamide;

2-chloro-N-{(1S)-1-[1 -(ethylsulfonyl)-4-(6-methylpyridin-2-yl)piperidin-4-yl]ethyl}-3,6-difluorobenzamide;

2,4-dichloro-N-{(1S)-1-[1 -(ethylsulfonyl)-4-(6-methylpyridin-2-yl)piperidin-4-yl]ethyl}benzamide;

2,4-dichloro-N-{[4-(3-methylpyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-({1-(propylsulfonyl)-4-[6-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}methyl)benzamide;

2,4-dichloro-N-({1-(propylsulfonyl)-4-[4-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}methyl)benzamide;

2,4-dichloro-N-{[4-(3-chloropyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{[4-(3-methoxypyridin-2-yl)-1-(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2-chloro-N-{[4-(3-chloropyridin-2-yl)-1 -(ethylsulfonyl)piperidin-4-yl]methyl}-3,6-difluorobenzamide;

2,4-dichloro-N-{[1-(ethylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-(1-{1 -[(3 -fluoropropyl)sulfonyl]-4-pyridin-2-ylpiperidin-4-y1}ethyl)benzamide;

2,4-dichloro-N-({1-[(3 -fluoropropyl)sulfonyl]-4-pyridin-2-ylpiperidin-4-y1}methyl)benzamide;

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

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

2,4-dichloro-N-{1-[4-(3 -fluoropyridin-2-yl)-1 -(propylsulfonyl)piperidin-4-yl]ethyl}benzamide;

2,4-dichloro-N-{[4-(6-trifluoromethylpyridin-2-yl)-1 -(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

4-bromo-2-chloro-N-{[1 -(ethylsulfonyl)-4-(3-fluoropyridin-2-yl)- piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{1 -[1 -(ethylsulfonyl)-4-(3-fluoropyridin-2-yl)- piperidin-4-yl]ethyl}benzamide;

2-bromo-4-fluoro-N-{[1 -(ethylsulfonyl)-4-(3-fluoropyridin-2-yl)- piperidin-4-yl]methyl}benzamide;

2-chloro-3,6-difluoro-N-{[1 -(ethylsulfonyl)-4-(3 -fluoropyridin-2-yl)- piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{[1 -(ethylsulfonyl)-4-(3 -trifluoromethylpyridin-2-yl)- piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-({1-[(3 -fluoropropyl)sulfonyl]-4-(3 -trifluoromethylpyridin-2-ylpiperidin-4-yl}methyl)benzamide;

2,4,6-trifluoro-N-{[1 -(ethylsulfonyl)-4-(3 -trifluoromethylpyridin-2-yl)- piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{[1 -(ethylsulfonyl)-4-(3 -trifluoromethylpyridin-2-yl)- piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{1 -[4-(3 -methylpyridin-2-yl)-1 -(propylsulfonyl)piperidin-4-1]ethyl}benzamide;

N-{[4-(3 -bromopyridin-2-yl)-1 -(propylsulfonyl)piperidin-4-yl]methyl}-2,4-dichlorobenzamide;

2,4-dichloro-N-{[4-(6-fluoropyridin-2-yl)-1 -(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-{[4-(6-chloropyridin-2-yl)-1 -(propylsulfonyl)piperidin-4-yl]methyl}benzamide;

2,4-dichloro-N-({1-(ethylsulfonyl)-4-[3-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}methyl)benzamide;

or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.

Assignments (16)