Claims for Patent: 7,893,075

Summary for Patent: 7,893,075

Title:	Compounds modulating c-fms and/or c-kit activity and uses therefor
Abstract:	Compounds active on the receptor protein tyrosine kinases c-kit and/or c-fms are provided herewith. Also provided herewith are compositions useful for treatment of c-kit mediated diseases or conditions and/or c-fms-mediated diseases or conditions, and methods for the use thereof.
Inventor(s):	Zhang; Jiazhong (Foster City, CA), Ibrahim; Prabha N. (Mountain View, CA), Artis; Dean R. (Kensington, CA), Bremer; Ryan (Oakland, CA), Wu; Guoxian (Palo Alto, CA), Zhu; Hongyao (Cedar Park, TX), Nespi; Marika (Berkeley, CA), Zhang; Chao (Moraga, CA)
Assignee:	Plexxikon, Inc. (Berkeley, CA)
Application Number:	11/986,667
Patent Claims:	1. A compound having the chemical structure of Formula III, ##STR00920## all salts, tautomers, and stereoisomers thereof, wherein: L.sub.4 is --CH.sub.2--, or, --C(O)--; R.sup.81 is selected from the group consisting of hydrogen, --CN, fluoro, chloro, lower alkyl, fluoro substituted lower alkyl, lower alkoxy, and fluoro substituted lower alkoxy; R.sup.82 is hydrogen; R.sup.83 is nitrogen containing heteroaryl, wherein nitrogen containing heteroaryl is optionally substituted with one or two substituents selected from the group consisting of halogen, lower alkyl, fluoro substituted lower alkyl, cycloalkylamino, --NHR.sup.41, --NR.sup.41R.sup.41, --OR.sup.41 and --S(O).sub.2R.sup.41; and R.sup.41 at each occurrence is lower alkyl or cycloalkyl, wherein lower alkyl is optionally substituted with one or more fluoro. 2. The compound of claim 1, selected from the group consisting of: Pyridin-3-ylmethyl-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]- -amine, 2,5-Dimethyl-2H-pyrazole-3-carboxylic acid [5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amide, (3-Chloro-pyridin-4-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-py- ridin-2-yl]-amine, (2-Methoxy-pyridin-3-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-p- yridin-2-yl]-amine, (6-Methoxy-pyridin-2-ylmethyl)-[5(1 H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine, (3,5-Dichloro-pyridin-4-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl- )-pyridin-2-yl]-amine, (6-Morpholin-4-yl-pyridin-2-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylme- thyl)-pyridin-2-yl]-amine, (5-Fluoro-pyridin-3-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-py- ridin-2-yl]-amine, (3-Chloro-pyridin-4-ylmethyl)-[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylm- ethyl)-pyridin-2-yl]-amine, (6-Methoxy-pyridin-3-ylmethyl)-[5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl- methyl)-pyridin-2-yl]-amine, 2-Methoxy-N-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-isonic- otinamide, N-[5-(1H-Pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-isonic- otinamide, Pyrazine-2-carboxylic acid [5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amide, 6-Methyl-N-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-nicotin- amide, 2-Chloro-N-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-i- sonicotinamide, (1-Methyl-1H-imidazol-4-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl- )-pyridin-2-yl]-amine, (1,5-Dimethyl-1H-pyrazol-3-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmet- hyl)-pyridin-2-yl]-amine, (3-Bromo-pyridin-4-ylmethl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyri- din-2-yl]-amine, (1H-Benzoimidazol-2-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-py- ridin-2-yl]-amine, (3-Fluoro-pyridin-2-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-py- ridin-2-yl]-amine, 3-{6-[(2-Methoxy-pyridin-3-ylmethyl)-amino]-pyridin-3-ylmethyl}-1H-pyrrol- o[2,3-b]pyridine-5-carbonitrile, [5-(5-Fluoro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-methox- y-pyridin-3-ylmethyl)-amine, (6-Methoxy-pyridin-3-ylmethyl)-[5-(5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-y- lmethyl)-pyridin-2-yl]-amine, (2-Morpholin-4-yl-pyridin-3-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylme- thyl)-pyridin-2-yl]-amine, Dimethyl-(5-{[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamino]-- methyl}-pyrimidin-2-yl)-amine, (5-Fluoro-pyridin-2-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-py- ridin-2-yl]-amine, (2,6-Dimethoxy-pyridin-3-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethy- l)-pyridin-2-yl]-amine, (6-Cyclopentyloxy-pyridin-3-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylme- thyl)-pyridin-2-yl]-amine, [6-Fluoro-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-methox- y-pyridin-3-ylmethyl)-amine, [5-(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-6-fluoro-pyridin-2-yl]-- (6-methoxy-pyridin-3-ylmethyl)-amine, Pyrimidin-5-ylmethyl-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-y- l]-amine, 2,2-Dimethyl-N-(3-{[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyri- din-2-ylamino]-methyl}-pyridin-2-yl)-propionamide, Methyl-(3-{[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamino]-me- thyl}-pyridin-2-yl)-amine, Methyl-(5-{[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamino]-me- thyl}-pyrimidin-2-yl)-amine, Dimethyl-(3-{[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamino]-- methyl}-pyridin-2-yl)-amine, (5-Chloro-pyridin-3-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-py- ridin-2-yl]-amine, [5-(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-[6-(2,2,2- -trifluoro-ethoxy)-pyridin-3-ylmethyl]-amine, and all salts or tautomers thereof. 3. A composition comprising: a pharmaceutically acceptable carrier; and a compound according to claim 1. 4. A kit comprising a composition according to claim 3. 5. The compound of claim 1, that is pyridine-2-carboxylic acid [5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethy)-pyridin-2-yl]-amide, and any pharmaceutically acceptable salts thereof. 6. The compound of claim 1 that is 5-methyl-pyrazine-2-carboxylic acid [5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amide, and any pharmaceutically acceptable salts thereof. 7. The compound of claim 1 that is [5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethy-pyridin-2-yl]-(6-trifluor- omethyl-pyridin-3-ylmethyl)-amine, and any pharmaceutically acceptable salts thereof. 8. The compound of claim 1 that is [5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-trifluoromethyl- -pyridin-3-ylmethyl)-amine, and any pharmaceutically acceptable salts thereof. 9. The compound of claim 1 that is (1-methyl-1H-benzoimidazol-2-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylm- ethyl)-pyridin-2-yl]-amine, and any pharmaceutically acceptable salts thereof. 10. The compound of claim 1 that is (6-methoxy-pyridin-3-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-p- yridin-2-yl]-amine, and any pharmaceutically acceptable salts thereof. 11. The compound of claim 1 that is (5-methoxy-pyridin-3-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-p- yridin-2-yl]-amine, and any pharmaceutically acceptable salts thereof. 12. The compound of claim 1 that is (3-fluoro-pyridin-4-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-py- ridin-2-yl]-amine, and any pharmaceutically acceptable salts thereof. 13. The compound of claim 1 that is 3-{6-[(3-chloro-pyridin-4-ylmethy)-amino]-pyridin-3-ylmethyl}-1H-pyrrolo[- 2,3-b]pyridine-5-carbonitrile, and any pharmaceutically acceptable salts thereof. 14. The compound of claim 1 that is 3-{6-[(6-trifluoromethyl-pyridin-3-ylmethyl)-amino]-pyridin-3-ylmethyl}-1- H-pyrrolo[2,3-b]pyridine-5-carbonitrile, and any pharmaceutically acceptable salts thereof. 15. The compound of claim 1 that is [5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-methox- y-pyridin-3-ylmethyl)-amine, and any pharmaceutically acceptable salts thereof. 16. The compound of claim 1 that is 3-{6-[(6-methoxy-pyridin-3-ylmethyl)-amino]-pyridin-3-ylmethyl}-1H-pyrrol- o[2,3-b]pyridine-5-carbonitrile, and any pharmaceutically acceptable salts thereof. 17. The compound of claim 1 that is (2-methoxy-pyridin-3-ylmethyl)-[5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl- methyl)-pyridin-2-yl]-amine, and any pharmaceutically acceptable salts thereof. 18. The compound of claim 1 that is [5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(2-methox- y-pyridin-3-ylmethyl)-amine, and any pharmaceutically acceptable salts thereof. 19. The compound of claim 1 that is [5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethy)-pyridin-2-yl]-(5-fluoro-- pyridin-3-ylmethyl)-amine, and any pharmaceutically acceptable salts thereof. 20. The compound of claim 1 that is [5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethy)-pyridin-2-yl]-[2-(2,2,2-trifluoro- -ethoxy)-pyridin-3-ylmethyl]-amine, and any pharmaceutically acceptable salts thereof. 21. The compound of claim 1 that is (2-methoxy-pyrimidin-5-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)- -pyridin-2-yl]-amine, and any pharmaceutically acceptable salts thereof. 22. A kit comprising a compound according to claim 1.