Claims for Patent: 8,404,700

Summary for Patent: 8,404,700

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):	Ibrahim; Prabha N. (Mountain View, CA), Artis; Dean R. (Kensington, CA), Bremer; Ryan (Emeryville, CA), Wu; Guoxian (Foster City, CA), Zhu; Hongyao (Berkeley, CA), Nespi; Marika (Berkeley, CA), Zhang; Chao (Moraga, CA), Zhang; Jiazhong (Burlingame, CA)
Assignee:	Plexxikon Inc. (Berkeley, CA)
Application Number:	13/546,923
Patent Claims:	1. A compound having the chemical structure of Formula III, ##STR00922## or all salts, prodrugs, tautomers, or stereoisomers thereof, wherein: L.sub.4 is --CH.sub.2 or --C(O)--; R.sup.81 is selected from the group consisting of --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, wherein R.sup.83 is pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, isoxazolyl, imidazolyl, or benzimidazolyl, each of which is optionally substituted with one or more 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. 3. The compound of claim 2, wherein R.sup.83 is optionally substituted with 1 or 2 substituents independently selected from fluoro, chloro, lower alkyl, fluoro substituted lower alkyl, lower alkoxy, fluorosubstituted lower alkoxy or cycloalkylamino. 4. The compound of claim 1, wherein R.sup.81 is chloro, methyl or CN. 5. A compound having the chemical structure of Formula III, ##STR00923## or all salts, prodrugs, tautomers, or 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 substituted with one or two substituents selected from the group consisting of 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. 6. A compound selected from the group consisting of: 2,5-Dimethyl-2H-pyrazole-3-carboxylic acid [5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amide, (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-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-p- yridin-2-yl]-amine, (6-Morpholin-4-yl-pyridin-2-ylmethyl)[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmet- hyl)-pyridin-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, (3-Bromo-pyridin-4-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylm- ethyl)-pyridin-2-yl]-amine, (1H-Benzoimidazol-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, (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, 2,2-Dimethyl-N-(3-{[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yla- mino]-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-(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-[6-(2,2,2- -trifluoro-ethoxy)-pyridin-3-ylmethyl]-amine, (1-methyl-1H-benzoimidazol-2-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylm- ethyl)-pyridin-2-yl]-amine, (5-methoxy-pyridin-3-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-p- yridin-2-yl]-amine, and all salts or tautomers thereof. 7. The compound of claim 6 that is (1-methyl-1H-benzoimidazol-2-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylm- ethyl)-pyridin-2-yl]-amine. 8. The compound of claim 5 that is (6-methoxy-pyridin-3-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-p- yridin-2-yl]-amine. 9. The compound of claim 1 that is [5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-triflu- oromethyl-pyridin-3-ylmethyl)-amine. 10. 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. 11. The compound of claim 1 that is 3-{6-[(3-chloro-pyridin-4-ylmethyl)-amino]-pyridin-3-ylmethyl}-1H-pyrrolo- [2,3-b]pyridine-5-carbonitrile. 12. 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. 13. 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. 14. 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. 15. 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. 16. 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. 17. The compound of claim 1 that is [5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(5-fluoro- -pyridin-3-ylmethyl)-amine. 18. The compound of claim 5 that is (2-methoxy-pyrimidin-5-ylmethyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)- -pyridin-2-yl]-amine. 19. A composition comprising: a compound according to claim 1 and a pharmaceutically acceptable carrier or excipient. 20. A composition comprising: a compound according to claim 5 and a pharmaceutically acceptable carrier or excipient. 21. A composition comprising: a compound according to claim 6 and a pharmaceutically acceptable carrier or excipient. 22. A kit comprising a composition according to claim 21.