TrkA kinase inhibitors, compositions and methods thereof

1. A compound of formula I:

and pharmaceutically acceptable salts thereof, wherein:

R represents hydrogen, or C 1-6 alkyl;

One of R 1 and R 2 is imidazopyridinyl and the other is selected from the group consisting of imidazopyridinyl, imidazopyridazinyl, imidazothiazolyl, or pyrazopyrimidinyl, said groups optionally substituted with 1 to 3 groups of R a

R a represents —CN, —O—, —(CH 2 ) n C 1-4 haloalkyl, —C 1-6 alkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —(CHR) n C 6-10 aryl, —(CHR) n C 5-10 heterocycle, —C 3-10 cycloalkyl, —O—(CH 2 ) n C 6-10 aryl, —O—C 5-10 heterocycle, —C(O)CF 3 , —(CH 2 ) n halo, —OR, —NRR, NHC 6-10 aryl, —SCF 3 , SO 2 CF 3 , OC(F) 2 Cl, OC 1-4 haloalkyl, C(O)NRR, SO 2 R, SO 2 NRR, OC(F) 2 C(F) 3 , S(O) 2 CH(F) 2 , OC(F) 2 CH(F) 2 , C(CH 3 ) 2 C≡N, —COC 6-10 aryl, or —CO 2 R, said cycloalkyl, alkyl, aryl and heterocycle optionally substituted with 1 to 3 groups of R b ,

R b represents, —CN, —(CH 2 ) n C 1-4 haloalkyl, —OR, —C 1-6 alkyl, (CH 2 ) n OR, —(CHR) n C 6-10 aryl, —(CHR) n C 5-10 heterocycle, —C 3-10 cycloalkyl, —(CH 2 ) n halo, said aryl and heterocycle optionally substituted with 1 to 3 groups of C 1-6 alkyl, or halo,

n represents 0-6; and

m represents 0.

2. The compound according to claim 1 wherein structural formula I is represented by structural formula II when R 1 is imidazopyridyl:

wherein R a and R 2 are as originally defined, or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 wherein one of R 1 and R 2 is optionally substituted imidazopyridinyl and the other is optionally substituted imidazopyridinyl, or imidazopyridazinyl, imidazothiazolyl.

4. The compound according to claim 1 wherein one of R 1 and R 2 is optionally substituted imidazopyridinyl and the other is optionally substituted imidazopyridinyl.

5. The compound according to claim 1 wherein one of R 1 and R 2 is optionally substituted imidazopyridinyl and the other is optionally substituted imidazopyridinyl.

6. A compound which is:

1,3-bis(2-phenylimidazo[1,2-a]pyridin-3-yl)urea;

1-naphthalen-1-yl-3-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)urea;

1-(2-methyl-4-phenylpyrimidin-5-yl)-3-(2-phenylimidazo[1,2-a]pyridin-3-yl)urea;

1-[2-chloro-4-(trifluoromethyl)phenyl]-3-(2-phenylimidazo[1,2-a]pyridin-3-yl)urea;

1-(2-phenylimidazo[1,2-a]pyridin-3-yl)-3-[4-(trifluoromethyl)phenyl]urea;

1-(2-phenylimidazo[1,2-a]pyridin-3-yl)-3-(2-phenylpyridin-3-yl)urea;

1-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-3-(2-phenylimidazo[1,2-a]pyridin-3-yl)urea;

1-(2-methyl-4-phenyl-1,3-thiazol-5-yl)-3-(2-phenylimidazo[1,2-a]pyridin-3-yl)urea;

1-[3-(1-methyl-1H-imidazol-2-yl)phenyl]-3-(2-phenylimidazo[1,2-a]pyridin-3-yl)urea;

ethyl 3-{[(2-phenylimidazo[1,2-a]pyridin-3-yl)carbamoyl]amino}imidazo[1,2-a]pyridine-2-carboxylate;

1-(2-phenylimidazo[1,2-a]pyridin-3-yl)-3-[2-(1H-pyrazol-1-yl)imidazo[1,2-a]pyridin-3-yl]urea;

1-(2-phenylimidazo[1,2-a]pyridin-3-yl)-3-(2-phenylimidazo[1,2-a]pyrimidin-3-yl)urea;

1-(6-chloro-2-phenylimidazo[1,2-b]pyridazin-3-yl)-3-(2-phenylimidazo[1,2-a]pyridin-3-yl)urea;

N-methyl-3-{[(2-phenylimidazo[1,2-a]pyridin-3-yl)carbamoyl]amino}imidazo[1,2-a]pyridine-2-carboxamide;

and pharmaceutically acceptable salts thereof.

7. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

8. A compound according to claim 1 for use as a medicament.

9. A method of treating a disease or disorder mediated by Trk receptors, wherein said disease or disorder is selected from the group consisting of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor Trk-A, Trk-B and/or Trk-C- in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.