4-Aryl-pyridine-2-carboxyamide derivatives

Abstract

The present invention relates to novel pyridine-2-carboxyamide derivatives of formula (I) useful as metabotropic glutamate receptor antagonists:

Description

Claims

1. A compound of formula (I)

2. The compound of claim 1 having formula (I′)

3. The compound of claim 1 wherein: Y is C—R4 and Z is CH; orY is C—R4 and Z is N; orY is N and Z is CH;R2 is H or C1-C7-alkyl;R3 is aryl or heteroaryl each of which is optionally substituted by one or more substituents independently selected from the group consisting of CN, Cl, F, CF3, C1-C7-alkyl, —O—C1-C7-alkyl, —(CH2)m—Rc, —O—CF3, and —S(O)2—Rd;R4 is H or C1-C7-alkyl;R5 is H, Cl, CN, CF3, CHF2, C1-C7-alkyl, C3-C6-cycloalkyl, —O(CO)—C1-C7-alkyl, —(CH2)m—Re or —(CO)—NRiRj;R6 is C1-C7-alkyl or —(CH2)m—Re;R7 is H, Cl, F, CN, or C1-C7-alkyl;Rc is OH;Rd is C1-C7-aklyl;Re is —CF3, CN, C1-C7-alkoxy, —O(CO)—C1-C7-alkyl or —(CO)—NRiRj;Ri and Rj are each independently H or C1-C7-alkyl; andm is 1;or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 having formula (Ia)

5. The compound of claim 4 selected from the group consisting of 4-(3-Fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(3-Cyano-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;6-Chloro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(2,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(3-Methoxy-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;6-Methyl-4-(3-trifluoromethoxy-phenyl)-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(3-Methanesulfonyl-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(4-Methoxy-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(3,4-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide; and6-Methyl-4-(3,4,5-trifluoro-phenyl)-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide.

6. The compound of claim 4 selected from the group consisting of 4-(4-Cyano-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(2-Methoxy-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(2-Chloro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(3-Hydroxymethyl-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;6′-Methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(3,5-Dichloro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;6-Methyl-4-pyrimidin-5-yl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(4-Fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;6-(3,5-Difluoro-phenyl)-2-methyl-pyrimidine-4-carboxylic acid (4-methyl-thiazol-2-yl)-amide; and2-Methyl-6-pyridin-3-yl-pyrimidine-4-carboxylic acid (4-methyl-thiazol-2-yl)-amide.

7. The compound of claim 4 selected from the group consisting of 4-(2,5-Dimethyl-2H-pyrazol-3-yl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;6′-Methyl-[2,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;6-Methyl-4-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;2-Chloro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;5-Cyano-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(3,5-Dimethyl-isoxazol-4-yl)-6-methyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4,6′-Dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;5-Methoxy-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;6-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide; and2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide.

8. The compound of claim 4 selected from the group consisting of 4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-trifluoromethyl-thiazol-2-yl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-trifluoromethyl-thiazol-2-yl)-amide;4-(3-Fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-trifluoromethyl-thiazol-2-yl)-amide;4-(3-Cyano-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-trifluoromethyl-thiazol-2-yl)-amide;4-(2-Chloro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-trifluoromethyl-thiazol-2-yl)-amide;6′-Methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-trifluoromethyl-thiazol-2-yl)-amide;2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (4-trifluoromethyl-thiazol-2-yl)-amide;4-(2,5-Dimethyl-2H-pyrazol-3-yl)-6-methyl-pyridine-2-carboxylic acid (4-trifluoromethyl-thiazol-2-yl)-amide;6′-Methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-difluoromethyl-thiazol-2-yl)-amide; and2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (4-difluoromethyl-thiazol-2-yl)-amide.

9. The compound of claim 4 selected from the group consisting of 4-(3-Chloro-4-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(3,5-Difluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;5-Fluoro-3′,6′-dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(4-Fluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;3′,6′-Dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;3,6-Dimethyl-4-pyrimidin-5-yl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide; and4-(3,4-Difluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide.

10. The compound of claim 4 selected from the group consisting of 4-(2,5-Dimethyl-2H-pyrazol-3-yl)-3,6-dimethyl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;2′-Chloro-3,6-dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;3,6,2′-Trimethyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;6′-Methyl-5-trifluoromethyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;2′-Fluoro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;6-Methyl-4-pyrazin-2-yl-pyridine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;2,6′-Dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;6,2′-Dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;6-Methyl-2-trifluoromethyl-[4,4]bipyridinyl-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;2′-Cyano-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide; and6′-Cyano-6,2′-dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide.

11. The compound of claim 4 selected from the group consisting of 2′-Chloro-5′-fluoro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;5,6′-Dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-cyanomethyl-thiazol-2-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-difluoromethyl-thiazol-2-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-cyano-thiazol-2-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methoxymethyl-thiazol-2-yl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-difluoromethyl-thiazol-2-yl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-cyano-thiazol-2-yl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-cydopentyl-thiazol-2-yl)-amide;6,2′-Dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (4-cyano-thiazol-2-yl)-amide; and6,2′-Dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methoxymethyl-thiazol-2-yl)-amide.

12. The compound of claim 4 selected from the group consisting of 6,2′-Dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;2-{[4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carbonyl]-amino}-thiazole-4-carboxylic acid methyl ester;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methylcarbamoyl-thiazol-2-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyrimidine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methoxymethyl-thiazol-2-yl)-amide;6,2′-Dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methoxymethyl-thiazol-2-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-methoxymethyl-thiazol-2-yl)-amide;6,2′-Dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (4-methoxymethyl-thiazol-2-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (5-methyl-thiazol-2-yl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-methoxymethyl-thiazol-2-yl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-cyanomethyl-thiazol-2-yl)-amide; and5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (5-fluoro-thiazol-2-yl)-amide.

13. The compound of claim 1 having formula (Ib)

14. The compound of claim 13 selected from the group consisting of 4-(3,5-Dichloro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide;4-(3-Chloro-4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide;4-(3,4-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide;6-(3,5-Difluoro-phenyl)-2-methyl-pyrimidine-4-carboxylic acid (2-methyl-thiazol-4-yl)-amide;5-Methoxy-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-methyl-thiazol-4-yl)-amide;6′-M ethyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-methyl-thiazol-4-yl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-methyl-thiazol-4-yl)-amide;4-(4-Fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide;2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide; and4-(2,5-Dimethyl-2H-pyrazol-3-yl)-6-methyl-pyridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide.

15. The compound of claim 13 selected from the group consisting of 4-(4-Fluoro-3-trifluoromethyl-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide;4-(2,5-Dimethyl-2H-pyrazol-3-yl)-3,6-dimethyl-p)yridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide;2′-Chloro-3,6-dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide;4-(3,5-Difluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide;3′,6′-Dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-methyl-thiazol-4-yl)-amide;4-(3-Chloro-4-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide;5-Fluoro-3′,6′-dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-methyl-thiazol-4-yl)-amide;3,6-Dimethyl-4-pyrimidin-5-yl-pyridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide;4-(4-Fluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide;4-(3,4-Difluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide; and2′-Fluoro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide.

16. The compound of claim 1 having formula (Ic)

17. The compound of claim 16 selected from the group consisting of 4-(3,5-Dichloro-phenyl)-6-methyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;4-(3-Chloro-4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;4-(3,4-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;4-(4-Fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;6-(3,5-Difluoro-phenyl)-2-methyl-pyrimidine-4-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;5-Methoxy-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;6′-Methyl-[3,4′]bipyridinyl-2′-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide; and4-(4-Fluoro-3-trifluoromethyl-phenyl)-6-methyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide.

18. The compound of claim 16 selected from the group consisting of 4-(4-Fluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;4-(3,5-Difluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;3′,6′-Dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;3,6-Dimethyl-4-pyrimidin-5-yl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;4-(3,4-Difluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;5-Fluoro-3′,6′-dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;4-(2,5-Dimethyl-2H-pyrazol-3-yl)-3,6-dimethyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;2′-Chloro-3,6-dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;6,2′-Dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide; and6,2′,6′-Trimethyl-[4,4′]bipyridinyl-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide.

19. The compound of claim 16 selected from the group consisting of 2′-Chloro-5′-fluoro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;5,6′-Dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;6,2′,5′-Trimethyl-[4,4′]bipyridinyl-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;6′-Cyano-6,2′-dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;2′-Cyano-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;(3-{[4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carbonyl]-amino}-pyrazol-1-yl)-acetic acid ethyl ester;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid [1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amide;6-Methyl-4-pyrimidin-5-yl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (1-carbamoylmethyl-1H-pyrazol-3-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (1-cyanomethyl-1H-pyrazol-3-yl)-amide; and4-(3,5-Difluoro-phenyl)-6-methyl-pyrimidine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide.

20. The compound of claim 1 having formula (Id)

21. The compound of claim 20 selected from the group consisting of: 4-(4-Fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-methyl-pyrimidin-4-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-methyl-pyrimidin-4-yl)-amide;6′-Methyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-methyl-pyrimidin-4-yl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-methyl-pyrimidin-4-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (4-chloro-pyrimidin-2-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-chloro-pyrimidin-4-yl)-amide;2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (2-methyl-pyrimidin-4-yl)-amide; and4-(3,5-Difluoro-phenyl)-6-methyl-pyrimidine-2-carboxylic acid (2-methyl-pyrimidin-4-yl)-amide.

22. The compound of claim 1 having formula (Ie)

23. The compound of claim 22 selected from the group consisting of 6′-Methyl-[3,4′]bipyridinyl-2′-carboxylic acid (6-methyl-pyridin-2-yl)-amide;6′-Methyl-[3,4′]bipyridinyl-2′-carboxylic acid (6-chloro-pyridin-2-yl)-amide;4-(3,5-Difluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (2-methyl-pyridin-4-yl)-amide;5-Fluoro-3′,6′-dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-methyl-pyridin-4-yl)-amide;3′,6′-Dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-methyl-pyridin-4-yl)-amide;4-(3-Chloro-4-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (2-methyl-pyridin-4-yl)-amide;4-(3,5-Difluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid (2-chloro-pyridin-4-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (5-cyano-pyridin-2-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (5-methyl-pyridin-2-yl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (5-chloro-pyridin-2-yl)-amide;2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (6-methyl-pyridin-2-yl)-amide;2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carbokylic acid (5-chloro-pyridin-2-yl)-amide; and2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (5-methyl-pyridin-2-yl)-amide.

24. The compound of claim 1 having formula (If)

25. The compound of claim 24 selected from the group consisting of 4-(4-Fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (3-chloro-phenyl)-amide;6′-Methyl-[3,4′]bipyridinyl-2′-carboxylic acid (3-cyano-phenyl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic-acid (3-cyano-phenyl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (3-cyano-phenyl)-amide;6,2′-Dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (3-cyano-phenyl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (3-chloro-phenyl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-fluoro-phenyl)-amide; and5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid phenylamide.

26. The compound of claim 1 having formula (Ig)

27. The compound of claim 26 selected from the group consisting of 4-(4-Fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-methyl-pyridin-4-yl)-amide;4-(4-Fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-chloro-pyridin-4-yl)-amide;6-(3,5-Difluoro-phenyl)-2-methyl-pyrimidine-4-carboxylic acid (2-chloro-pyridin-4-yl)-amide;6-(3,5-Difluoro-phenyl)-2-methyl-pyrimidine-4-carboxylic acid (2-methyl-pyridin-4-yl)-amide;5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-chloro-pyridin-4-yl)-amide;4-(3,4-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-chloro-pyridin-4-yl)-amide;6′-Methyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-chloro-pyridin-4-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-chloro-pyridin-4-yl)-amide;4-(3-Chloro-4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-chloro-pyridin-4-yl)-amide;4-(3,4-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-methyl-pyridin-4-yl)-amide; and5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-methyl-pyridin-4-yl)-amide.

28. The compound of claim 26 selected from the group consisting of 4-(3-Chloro-4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-methyl--pyridin-4-yl)-amide;6′-Methyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-methyl-pyridin-4-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-methyl-pyridin-4-yl)-amide;5-Cyano-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-methyl-pyridin-4-yl)-amide;4-(2,5-Dimethyl-2H-pyrazol-3-yl)-6-methyl-pyridine-2-carboxylic acid (5-chloro-pyridin-2-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (5-chloro-pyridin-2-yl)-amide;4-(3-Chloro-4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (5-choro-pyridin-2-yl)-amide;6′-Methyl-[3,4′]bipyridinyl-2′-carboxylic acid (5-chloro-pyridin-2-yl)-amide;2′-Cyano-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (2-methyl-pyridin-4-yl)-amide;6′-Cyano-6,2′-dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (2-methyl-pyridin-4-yl)-amide; and6,2′-Dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (2-methyl-pyridin-4-yl)-amide.

29. The compound of claim 26 selected from the group consisting of 2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (2-methyl-pyridin-4-yl)-amide;6′-Cyano-6,2′-dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (2-chloro-pyridin-4-yl)-amide;2′-Cyano-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (2-chloro-pyridin-4-yl)-amide;6,2′-Dimethyl-[4,4′]bipyridinyl-2-carboxylic acid (2-chloro-pyridin-4-yl)-amide;6,2′,6′-Trimethyl-[4,4′]bipyridinyl-2-carboxylic acid (2-chloro-pyridin-4-yl)-amide;5,6′-Dimethyl-[3,4′]bipyridinyl-2′-carboxylic acid (2-chloro-pyridin-4-yl)-amide;2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid (2-chloro-pyridin-4-yl)-amide;6,2′,5′-Trimethyl-[4,4′]bipyridinyl-2-carboxylic acid (2-chloro-pyridin-4-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid (2-cyano-pyridin-4-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyrimidine-2-carboxylic acid (2-chloro-pyridin-4-yl)-amide;4-(3,5-Difluoro-phenyl)-6-methyl-pyrimidine-2-carboxylic acid (2-methyl-pyridin-4-yl)-amide; and4-(3,5-Difluoro-phenyl)-6-methyl-pyrimidine-2-carboxylic acid (2-cyano-pyridin-4-yl)-amide.

30. The compound of claim 1 having formula (Ih)

31. The compound of claim 30 which is 5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid pyridin-3-ylamide.

32. The compound of claim 1 having formula (Ii)

33. The compound of claim 32 which is 5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid (4-fluoro-phenyl)-amide.

34. A pharmaceutical composition comprising a compound of formula I