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|Title:||Compounds modulating c-kit and c-fms activity and uses therefor|
|Abstract:||Compounds active on the receptor protein tyrosine kinases c-kit and c-fms are provided herewith. Also provided herewith are compositions useful for treatment of c-kit mediated diseases or condition and c-fms-mediated diseases or condition, and methods for the use thereof.|
|Inventor(s):||Zhang; Chao (Moraga, CA), Zhang; Jiazhong (Oakland, CA), Ibrahim; Prabha N. (Mountain View, CA), Hurt; Clarence R. (San Ramon, CA), Zuckerman; Rebecca (Alameda, CA), Artis; Dean R. (Kensington, CA), Bremer; Ryan (Emeryville, CA), Spevak; Wayne (Berkeley, CA), Wu; Guoxian (Palo Alto, CA), Zhu; Hongyao (Berkeley, CA)|
|Assignee:||Plexxikon, Inc. (Berkeley, CA)|
|Filing Date:||May 16, 2006|
|Claims:||1. A compound having the chemical structure ##STR00223## all salts, tautomers, and stereoisomers thereof, wherein: X.sub.1 is CR.sup.2, X.sub.2 is CR.sup.6, Y.sub.1 is CR.sup.4, and Y.sub.2 is CR.sup.5; L.sup.1 is --CH.sub.2--; L.sup.2 is selected from the group consisting of --O--CH.sub.2--, --NH--CH.sub.2, --NH--CH(CH.sub.3)--, and --NH--C(O); R.sup.1 is cycloalkyl or phenyl, wherein phenyl is substituted with a substituent selected from the group consisting of fluoro, chloro, methyl, methoxy and trifluoromethyl; R.sup.2 and R.sup.6 are hydrogen; one of R.sup.4 and R.sup.5 is selected from the group consisting of fluoro, chloro, bromo, lower alkyl optionally substituted with one or more fluoro, lower alkenyl, lower alkynyl, cycloalkyl, --CN, and lower alkoxy optionally substituted with one or more fluoro, lower alkoxy, di-alkylamino or cycloalkylamino, and the other of R.sup.4 and R.sup.5 is selected from the group consisting of hydrogen, fluoro, chloro, bromo, lower alkyl optionally substituted with one or more fluoro, lower alkenyl, lower alkynyl, cycloalkyl, --CN, and lower alkoxy optionally substituted with one or more fluoro, lower alkoxy, dialkylamino, or cycloalkylamino; Ar.sub.1 is a 6 membered optionally substituted heteroarylene having the structure ##STR00224## wherein ##STR00225## indicates the point of attachment of L.sup.1 and ##STR00226## indicates the point of attachment of L.sup.2, and wherein the indicated N is either .dbd.N-- or --N.dbd.; n is 1; F and J are both C; P is CR and Q is CH, wherein R is hydrogen, methyl or methoxy; T is CH. |
2. The compound according to claim 1, wherein Y.sub.1 is CH and Y.sub.2 is CR.sup.5.
3. The compound according to claim 2, wherein R.sup.5 is fluoro, chloro, lower alkyl or lower alkoxy.
4. The compound according to claim 2, wherein R.sup.5 is chloro or methoxy.
5. The compound according to claim 1, wherein Y.sub.2 is CH and Y.sub.1 is CR.sup.4.
6. The compound according to claim 5, wherein R.sup.4 is fluoro, chloro, lower alkyl or lower alkoxy.
7. The compound according to claim 5, wherein R.sup.4 is chloro or methoxy.
8. A composition comprising: a pharmaceutically acceptable carrier; and a compound according to claim 1.
9. A kit comprising a composition according to claim 8.
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