Amides useful for treating pain

1. A compound of formula (I)

or a pharmaceutically acceptable salt or prodrug thereof, wherein

A is

X 1 is N or CR 1 ;

X 2 is N or CR 2 ;

X 3 is S, O or N;

R is absent or O;

R 1 is hydrogen, lower alkoxy, lower alkenyl, lower alkyl, lower alkylthio, lower alkynyl, lower haloalkoxy, lower haloalkyl, lower haloalkylthio, halogen, hydroxy, mercapto, nitro, R A R B NS(O) 2 — or R A R B N—;

R 2 , R 3 , and R 4 are independently hydrogen or halogen;

R 7 is hydrogen, alkenyl, alkoxy, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkoxycarbonylalkyl, alkylsulfonyl, alkylthio, alkynyl, aryl, arylalkyl, aryloxy, arylthio, cyanoalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, cycloalkylthio, haloalkoxy, haloalkyl, haloalkylsulfonyl, haloalkylthio, halogen, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, —R C R D N—, (R A R B N)carbonyl-, (R A R B N)sulfonyl- ; or R A S(O) 2— ;

R 6 and R 8 are independently hydrogen, lower alkenyl, lower alkoxy, lower alkyl, lower alkylthio, lower alkynyl, lower haloalkoxy, lower haloalkyl, lower haloalkylthio, halogen, hydroxy, mercapto, or R A R B N—;

alternatively, R 7 and R 6 taken together with the atoms they are attached can form a ring selected from the group consisting of 2,2,3,3-tetrafluoro-2,3-dihydro-benzo[1,4]dioxinyl; 2,3-tetrahydro-benzo[1,4]dioxinyl; 2,2-difluoro-benzo[1,3]dioxolyl; and 2,2-dihydro-benzo[1,3]dioxolyl;

R A and R B are independently alkyl, hydrogen, haloalkyl, or heterocycle;

R C and R D are independently hydrogen, alkenyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkynyl, or (NR A R B )carbonyl;

L is

— is absent or a single bond; and

R 11 , R 12 , R 13 , and R 14 are independently hydrogen, alkoxy, alkyl, or hydroxy.

2. The compound according to claim 1 of formula (II)

or a pharmaceutically acceptable salt or prodrug thereof.

3. The compound according to claim 2 wherein

— is a single bond;

X 1 is CR 1 ;

X 2 is CR 2 ;

R 1 is lower haloalkyl, halogen, or R A R B NS(O) 2 —;

R 2 , R 3 , and R 4 are hydrogen;

R 7 is alkoxy, alkyl, alkylthio, alkylcarbonyl, hydroxyalkyl, alkylcarbonylalkyl, cycloalkyl, haloalkoxy, haloalkyl, haloalkylsulfonyl, haloalkylthio, halogen, R C R D N—; or R A S(O) 2 —;

R 11 , R 12 , R 13 , and R 14 are hydrogen; and

R C and R D are independently hydrogen or alkyl.

4. The compound according to claim 3 that is

N-(4-tert-butylphenyl)-3′-chloro-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-(4-methylphenyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-(4-methoxyphenyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-(4-fluorophenyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

N-(4-bromophenyl)-3′-chloro-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-[4-(trifluoromethoxy)phenyl]-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-(4-ethylphenyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-(4-isopropylphenyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-(4-propoxyphenyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-[4-(methylthio)phenyl]-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-(3-fluoro-4-methylphenyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-[4-(trifluoromethyl)phenyl]-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-[4-(dimethylamino)phenyl]-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-[4-(diethylamino)phenyl]-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

N-(4-tert-butylphenyl)-1-(3-chloro-2-pyridinyl)-(cis)-3-hydroxy-4-piperidinecarboxamide;

N-(4-tert-butylphenyl)-1-(3-chloro-2-pyridinyl)-(trans)-3-hydroxy-4-piperidinecarboxamide;

1-(3-chloro-2-pyridinyl)-4-hydroxy-N-[4-(trifluoromethyl)phenyl]-4-piperidinecarboxamide.

N-(4-tert-butylphenyl)-3′-(trifluoromethyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

N-(4-chlorophenyl)-3′-(trifluoromethyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

N-[4-(trifluoromethoxy)phenyl]-3′-(trifluoromethyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-(trifluoromethyl)-N-{4-[(trifluoromethyl)thio]phenyl}-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-(trifluoromethyl)-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

N-(3 -fluoro-4-methylphenyl)-3′-(trifluoromethyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-bromo-3-fluoro-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-bromo-3-methyl-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-chloro-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-trifluoromethylsulfanyl-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-trifluoromethoxy-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-bromo-3-chloro-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-bromo-3-trifluoromethyl-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-chloro-3-fluoro-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (3,4-dichloro-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-chloro-3-methyl-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-chloro-3-trifluoromethyl-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-difluoromethyoxy-phenyl)-amide;

3-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(1,1,2,2-tetrafluoro-ethoxy)-phenyl]-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (3-chloro-4-methyl-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (3-bromo-4-methyl-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-methyl-3-trifluoromethyl-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-trifluoromethylsulfanyl-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (3-fluoro-4-trifluoromethyl-phenyl)-amide

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (3,4-dimethyl-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-tert-butyl-3-fluoro-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-chloro-3-fluoro-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-tert-butyl-3-fluoro-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(1-hydroxy-1-methyl-ethyl)-phenyl]-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(ethyl-isopropyl-amino)-phenyl]-amide hydrochloride;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-cyclopropyl-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-amide;

Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(2,2-dichloro-1-methyl-cyclopropyl)-phenyl]-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (3,4-difluorophenyl)-amide;

2-Methyl-2-{4-[(3′-trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carbonyl)-amino]-phenyl}-propionic acid methyl ester;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(2-hydroxy-1,1-dimethyl-ethyl)-phenyl]-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2 ′]bipyridinyl-4-carboxylic acid (4-acetyl-phenyl)-amide;

4-[(3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carbonyl)-amino]-benzoic acid methyl ester;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-trifluoromethyl-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-tert-butylsulfanyl-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(2-methyl-propane-2-sulfonyl)-phenyl]-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-trifluoromethanesulfonyl-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2 ′]bipyridinyl-4-carboxylic acid [4-(cyano-dimethyl-methyl)-phenyl]-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(cyano-dimethyl-methyl)-phenyl]-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (3-chloro-4-trifluoromethylsulfanyl-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-dimethylsulfamoyl-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(piperidine-1-sulfonyl)-phenyl]-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

3′-Dimethylsulfamoyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-tert-butyl-phenyl)-amide;

3′-Dimethylsulfamoyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-chloro-phenyl)-amide; or

3′-Dimethylsulfamoyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-trifluoromethoxy-phenyl)-amide.

5. The compound according to claim 3 that is 3′-chloro-N-(4-chlorophenyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide.

6. The compound according to claim 2 wherein

— is a single bond;

X 1 is CR 1 ;

X 2 is CR 2 ;

R 1 is lower haloalkyl or halogen;

R 2 , R 3 , and R 4 are hydrogen;

R 7 is aryl or aryloxy; and

R 11 , R 12 , R 13 , and R 14 are hydrogen.

7. The compound according to claim 6 that is

3′-chloro-N-(4-phenoxyphenyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide; or

N-1,1′-biphenyl-4-yl-3′-chloro-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide.

8. The compound according to claim 2 wherein

— is a single bond;

X 1 is CR 1 ;

X 2 is CR 2 ;

R 1 is lower haloalkyl or halogen;

R 2 , R 3 , and R 4 are hydrogen;

R 7 is heterocycle; and

R 11 , R 12 , R 13 , and R 14 are hydrogen.

9. The compound according to claim 8 that is

3′-chloro-N-[4-(1-piperidinyl)phenyl]-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-chloro-N-[4-(4-morpholinyl)phenyl]-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

N-[4-(1-azepanyl)phenyl]-3′-chloro-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-azepan-1-yl-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-azepan-1-yl-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(8-aza-bicyclo[3.2.1]oct-8-yl)-phenyl]-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(8-aza-bicyclo[3.2.1]oct-8-yl)-3-fluoro-phenyl]amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(8-aza-bicyclo[3.2.1]oct-8-yl)-3,5-difluoro-phenyl]amide; or

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid [4-(8-aza-bicyclo[3.2.1]oct-8-yl)-3,5-difluoro-phenyl]-amide.

10. The compound according to claim 2 , wherein R 7 and R 8 taken together with the atoms they are attached can form a ring selected from the group consisting of 2,2,3,3-tetrafluoro-2,3-dihydro-benzo[1,4]dioxinyl; 2,3-tetrahydro-benzo[1,4]dioxinyl; 2,2-difluoro-benzo[1,3]dioxolyl; and 2,2-dihydro-benzo[1,3]dioxol

11. The compound according to claim 10 that is

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (2,2,3,3-tetrafluoro-2,3-dihydro-benzo[1,4]dioxin-6-yl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (2,2-difluoro-benzo[1,3]dioxol-5-yl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (2,2-difluoro-benzo[1,3]dioxol-5-yl)-amide.

12. The compound according to claim 2 wherein

— is a single bond;

X 1 is CR 1 ;

X 2 is CR 2 ;

R 1 is lower haloalkyl or halogen;

R 2 , R 3 , and R 4 are hydrogen;

R 6 is lower alkyl, lower haloalkyl, or halogen; and

R 7 , R 8 , R 11 , R 12 , R 13 , and R 14 are hydrogen.

13. The compound according to claim 12 that is

N-(3-tert-butylphenyl)-3′-chloro-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide; or

3′-chloro-N-(3-fluorophenyl)-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide.

14. The compound according to claim 2 wherein

— is a single bond;

X 1 is N;

X 2 is CR 2 ;

R 2 , R 3 , and R 4 are hydrogen;

R 7 is alkoxy, alkyl, alkylthio, haloalkoxy, haloalkyl, haloalkylsulfonyl, haloalkylthio, halogen, or R C R D N—;

R 11 , R 12 , R 13 , and R 14 are hydrogen; and

R C and R D are independently hydrogen or alkyl.

15. The compound according to claim 12 that is

N-(4-chlorophenyl)-1-pyrimidin-2-yl-1,2,3,6-tetrahydropyridine-4-carboxamide;

1-pyrimidin-2-yl-N-{4-[(trifluoromethyl)thio]phenyl}-1,2,3,6-tetrahydropyridine-4-carboxamide;

1-pyrimidin-2-yl-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-1,2,3,6-tetrahydropyridine-4-carboxamide;

1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-tert-butyl-phenyl)-amide;

1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-chloro-phenyl)-amide;

1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-trifluoromethyoxy-phenyl)-amide;

1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-trifluoromethylsulfanyl-phenyl)-amide;

1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-trifluoromethanesulfonyl-phenyl)-amide; 1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-tert-butyl-3-fluoro-phenyl)-amide;

1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-trifluoromethyl-phenyl)-amide;

1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine4-carboxylic acid (4-chloro-3-fluoro-phenyl)-amide;

2-Methyl-2-{4-[(1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carbonyl)-amino]-phenyl}-propionic acid methyl ester;

1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-acetyl-phenyl)-amide;

4-[(1-Pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carbonyl)-amino]-benzoic acid methyl ester;

1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid [4-(2-methyl-propane-2-sulfonyl)-phenyl]-amide;

1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-tert-butylsulfanyl-phenyl)-amide; or

1-(4-Methoxy-pyrimidin-2-yl)-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-trifluoromethyl-phenyl)-amide.

16. The compound according to claim 2 wherein

— is a single bond;

X 1 is N;

X 2 is CR 2 ;

R 2 , R 3 , and R 4 are hydrogen;

R 7 is heterocycle;

R 11 , R 12 , R 13 , and R 14 are hydrogen; and

R C and R D are independently hydrogen or alkyl.

17. The compound according to claim 16 that is

1-Pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid [4-(8-aza-bicyclo[3.2.1]oct-8-yl)-3-fluoro-phenyl]-amide;

1-Pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid [4-(8-aza-bicyclo[3.2.1]oct-8-yl)-3,5-difluoro-phenyl]-amide; or

1-Pyrimidin-2-yl- 1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-azepan-1-yl-phenyl)-amide.

18. A compound of formula (III)

— is a single bond;

X 1 is CR 1 ;

X 2 is CR 2 ;

R 1 is hydrogen, lower haloalkyl or halogen;

R 2 , R 3 , R 4 , and R 6 , are hydrogen;

R 5 is alkyl, hydrogen, halogen, alkoxy, or haloalkoxy;

R 7 is alkoxy, alkyl, alkylthio, cycloalkyl, haloalkoxy, haloalkyl, haloalkylsulfonyl, haloalkylthio, halogen, R C R D N—; or R A S(O) 2 —;

R 11 , R 12 , R 13 , and R 14 are hydrogen; and

R A , R C and R D are independently hydrogen or alkyl.

19. The compound according to claim 18 that is

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-bromo-2-chloro-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-bromo-2-fluoro-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-bromo-2-methyl-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (2-fluoro-4-iodo-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-chloro-2-trifluoromethyl-phenyl)-amide;

3′-Trifluoromethyl-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-tert-butyl-2-chloro-phenyl)-amide;

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-tert-butyl-2-fluoro-phenyl)-amide; or

3′-Chloro-3,6-dihydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (4-chloro-2-fluoro-phenyl)-amide.

20. The compound according to claim 1 of formula (IV)

or a pharmaceutically acceptable salt or prodrug thereof.

21. The compound according to claim 20 wherein

X 1 is CR 1 ;

X 2 is CR 2 ;

R 1 is lower haloalkyl or halogen;

R 2 , R 3 , and R 4 are hydrogen;

R 7 is alkoxy, alkyl, alkylthio, haloalkoxy, haloalkyl, haloalkylthio, halogen, or R C R D N—;

R 11 , R 12 , R 13 , and R 14 are hydrogen; and

R C and R D are independently hydrogen or alkyl.

22. The compound according to claim 21 that is

N-(4-tert-butylphenyl)-3-(3-chloro-2-pyridinyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxamide;

3-(3-chloro-2-pyridinyl)-N-(3,4-dichlorophenyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxamide;

3-(3-chloro-2-pyridinyl)-N-[4-(trifluoromethyl)phenyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxamide;

3-(3-chloro-2-pyridinyl)-N-(4-fluorophenyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxamide;

N-(4-chlorophenyl)-3-(3-chloro-2-pyridinyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxamide;

N-(4-bromophenyl)-3-(3 -chloro-2-pyridinyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxamide;

3-(3-chloro-2-pyridinyl)-N-(4-iodophenyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxamide;

N-(4-butylphenyl)-3-(3-chloro-2-pyridinyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxamide;

3-(3-chloro-2-pyridinyl)-N-(4-isopropylphenyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxamide; or

3-(3-chloro-2-pyridinyl)-N-{4-[(trifluoromethyl)thio]phenyl}-3,8-diazabicyclo[3.2.1]octane-8-carboxamide.

23. The compound according to claim 20 wherein

X 1 is CR 1 ;

X 2 is CR 2 ;

R 1 is lower haloalkyl or halogen;

R 2 , R 3 , and R 4 are hydrogen;

R 6 is lower alkyl, lower haloalkyl, or halogen; and

R 7 , R 8 , R 11 , R 12 , R 13 , and R 14 are hydrogen.

24. The compound according to claim 23 that is 3-(3-chloro-2-pyridinyl)-N-[3-(trifluoromethyl)phenyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxamide.

25. The compound according to claim 1 of formula (V)

or a pharmaceutically acceptable salt or prodrug thereof.

26. The compound according to claim 25 wherein

X 1 is CR 1 ;

X 2 is CR 2 ;

R 1 is lower alkyl or halogen;

R 2 , R 3 , and R 4 are hydrogen;

R 7 is alkoxy, alkyl, alkylthio, haloalkoxy, haloalkyl, haloalkylthio, halogen, or R C R D N—;

R 11 , R 12 , R 13 , and R 14 are hydrogen; and

R C and R D are independently hydrogen or alkyl.

27. The compound according to claim 26 that is

N-(4-tert-butylphenyl)-8-(3-chloro-2-pyridinyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxamide; or

3-chloro-2-pyridinyl)-N-[4-(trifluoromethyl)phenyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxamide.

28. The compound according to claim 1 of formula (VI)

wherein

X 3 is S;

R 2 , and R 3 are independently hydrogen or halogen;

R 7 is hydrogen, alkenyl, alkoxy, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkoxycarbonylalkyl, alkylsulfonyl, alkylthio, alkynyl, aryl, arylalkyl, aryloxy, arylthio, cyanoalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, cycloalkylthio, haloalkoxy, haloalkyl, haloalkylsulfonyl, haloalkylthio, halogen, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, R C R D N—, (R A R B N)carbonyl-, (R A R B N)sulfonyl-; or R A S(O) 2 —;

R 6 and R 8 are independently hydrogen, lower alkenyl, lower alkoxy, lower alkyl, lower alkylthio, lower alkynyl, lower haloalkoxy, lower haloalkyl, lower haloalkylthio, halogen, hydroxy, mercapto, or R A R B N—; and

R A and R B are independently alkyl, hydrogen, halogen, haloalkyl, or heterocycle.

29. The compound according to claim 28 that is

1-Thiazol-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-trifluoromethanesulfonyl-phenyl)-amide; or

1-Thiazol-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-tert-butyl-phenyl)-amide.

30. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

31. A method of treating pain in a mammal, comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

32. A pharmaceutical compostion comprising a therapeutically effective amount of 3-(trifluoromethyl)-N-{4-[(trifluoromethyl)sulfonyl]-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide or a pharmaceutically acceptable salt thereof.

33. A method of treating pain in a mammal, comprising administering a therapeuitcally effective amount of 3′-(trifluoromethyl)-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-3,6-dihydro-2H-1,2′-bipyridine-4-carboxamide or a pharmaceutically acceptable salt thereof.