Triarylimidazole derivatives as cytokine inhibitors

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

wherein R 1 is naphthyl, or phenyl optionally substituted with one or more substituents selected from the group consisting of halo, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 1-6 alkyl, C 1-6 haloakyl, —O—(CH 2 ) n -Ph, —S—(CH 2 ) n -Ph, cyano, phenyl, and CO 2 R, wherein R is hydrogen or C 1-6 alkyl, and n is 0, 1, 2 or 3; or R 1 is phenyl fused with an aromatic or non-aromatic cyclic ring of 5-7 members wherein said cyclic ring optionally contains up to three heteroatoms, independently selected from N, O and S;

R 2 is H, C 1-6 alkyl, C 1-6 alkoxy, phenyl, NH(CH 2 ) n -Ph, NH—C 1-6 alkyl, halo or alkoxy;

R 3 is COOH, tetrazole, CN, NO 2 , OH, —S—C 1-6 alkyl, —SO—C 1-6 alkyl, —O—C 1-6 alkyl, SONH 2 , CHO, CH 2 OH, (CH 2 ) n NH 2 , CONHOR′, O(CH 2 ) n CO 2 R′, O(CH 2 ) n CONHR′, CONHR′, (CH 2 ) n CO 2 R′, or (CH 2 ) n CONHR′ wherein R′ is hydrogen or C 1-6 alkyl, and n is 0, 1, 2 or 3; and

one of X 1 and X 2 is N or CR″, and the other is NR″ or CHR″ wherein R″ is hydrogen, C 1-6 alkyl, or C 3-7 cycloalkyl; or when one of X 1 and X 2 is N or CR″ then the other may be S or O;

provided that the compound is not one in which R 1 is naphthyl, or phenyl optionally substituted with one or more substituents selected from the group consisting of halo, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 1-6 alkyl, —O—(CH 2 ) n -Ph, —S—(CH 2 ) n -Ph, cyano, phenyl, and CO 2 R, wherein R is hydrogen or C 1-6 alkyl and n is 0, 1, 2 or 3; or R 1 is phenyl fused with an aromatic or non-aromatic cyclic ring of 5-7 members wherein said cyclic ring optionally contains up to two heteroatoms, independently selected from N, O and S;

and R 2 is H, NH(CH 2 ) n -Ph or NH—C 1-6 alkyl; and

and R 3 is CO 2 H, CONH 2 , CN, NO 2 , C 1-6 alkylthio, SO 2 —C 1-6 alkyl, C 1-6 alkoxy, SONH 2 , CONHOH, NH 2 , CHO, CH 2 OH, CH 2 NH 2 , or CO 2 R, wherein R is hydrogen or C 1-6 alkyl.

2. A compound according to claim 1 wherein R 1 is phenyl optionally substituted with one or more substituents selected from the group consisting of halo, C 1-6 alkoxy, C 1-6 alkylthio, and phenyl; or R 1 is phenyl fused with an aromatic or non-aromatic cyclic ring of 5-7 members wherein said cyclic ring optionally contains up to two heteroatoms, independently selected from N, O and S.

3. A compound according to claim 1 wherein R 2 is other then hydrogen and is positioned ortho to the nitrogen of the pyridyl ring.

4. A compound according to claim 1 wherein R 3 is CO 2 H, CONH 2 , CONHOH, CH 2 OH, CN or tetrazole.

5. A compound according to claim 1 wherein one of X 1 and X 2 is N or CR″, and the other is NR″ or CHR″ wherein R″ is hydrogen, C 1-6 alkyl, or C 3-7 cycloalkyl, provided that at least one of X 1 and X 2 is N or NR″; or one of one of X 1 and X 2 is N and the other is O.

6. A compound according to claim 5 wherein one of X 1 and X 2 is N and the other is NR″.

7. A compound according to claim 1 wherein each R′ is hydrogen.

8. A compound according to claim 1 selected from:

4-(4-Benzo[1,3]dioxol-5-yl-5-pyridin-2-yl-1H-imidazol-2-yl)phenol;

4-(4-Benzo[1,3]dioxol-5-yl-5-pyridin-2-yl-1H-imidazol-2-yl)-N-methyl-benzamide;

4-(4-Benzo[1,3]dioxol-5-yl-5-pyridin-2-yl-1H-imidazol-2-yl)-N-methoxy-benzamide;

2-{4Benzo[1,3]dioxol-5-yl-2-[4-(2H-tetrazol-5-yl)-phenyl]-1H-imidazol-5-yl}-pyridine;

[4-(4-Benzo[1,3]dioxol-5-yl-5-pyridin-2-yl-1H-imidazol-2-yl)-phenoxy]-acetic acid;

4-[4-(4-Fluoro-3-methoxyphenyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]-benzonitrile;

4-[4-(4-Fluoro-3-methoxyphenyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]-benzamide;

4-[4-(3-Fluoro-4-methoxyphenyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]benzonitrile;

4-[4-(3-Fluoro-4-methoxyphenyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]benzamide;

4-[4-Benzo[1,2,5]oxadiazol-5-yl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl]benzonitrile;

4-[4-Benzo[1,2,5]oxadiazol-5-yl-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]benzamide;

4-[4-(6-Methoxynaphthalen-2-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]benzonitrile;

4-[4-(6-Methoxynaphthalen-2-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]benzamide;

4-[4-Benzo[1,2,5]thiadiazol-5-yl-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]benzonitrile;

4-[4-Benzo[1,2,5]thiadiazol-5-yl-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]benzamide;

4-[4-Benzo[1,3]dioxol-5-yl-5-(6-methylpyridin-2-yl-1H-imidazol-2-yl]benzonitrile;

4-[4-Benzo[1,3]dioxol-5-yl-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]benzamide;

6-[2-(4-Cyanophenyl)-5-(6-methylpyridin-2-yl)-1H-imidazole-4-yl]-quinoxaline; and

6-[2-(4-Carboxamidophenyl)-5-(6-methylpyridin-2-yl)-1H-imidazole-4-yl]-quinoxaline;

and pharmaceutically acceptable salts thereof.

9. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.