Pyrimidine derivatives as kinase modulators and method of use

Abstract

The invention provides compounds and methods for inhibition of kinases, more specifically IGF 1 R kinases. The invention also provides compounds and methods for inhibition of wildtype Abl. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinase receptor signal transduction pathways related to the changes in cellular activities as mentioned above, and the invention includes compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein, V is NRR, or O—R, wherein X is H, halo, C-Calkyl, NO, mono-, di-, or tri-halo substituted methyl, NRR,. C(O)O—C-Calkyl, or N(R)—C(O)—C-Calkyl; Y is H, halo, OH, C-Calkyl, C-Calkyl-NR,R, NRR,, C-Calkoxy, —N(R)—(CH)NRR, —C(O)O—C-Calkyl, —O—(CH)—NRR, —C(O)—C-Calkyl, —C-C-alkyl-R, —O—R, —C(O)—R, —O—(CH)—R, —C(O)—NRR, —C(O)—N(R)-aryl, —C(O)—N(R)(CH)—NRR, —C(O)—N(R)—(CH)-aryl —C(O)—N(R)—(CH)-heterocyclyl; or X and Y together with the atoms to which they are attached form a 4-7 membered heterocyclyl or heteroaryl group containing one or two heteroatoms independently selected from O, N, and S. Z is H, NRR, —S—R, or —O—R