COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR

摘要

Compounds active on c-kit protein kinases or mutant c-kit protein kinases having any mutations are described, as well as methods of making and using such compounds to treat diseases and conditions associated with aberrant activity of the c-kit protein kinases and/or mutant c-kit protein kinases.

主权项

1. A compound of Formula (I): or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein: Z is N or CR1; Q1 is N or CR2, wherein R2 is H, halogen, CH3, CH3O, or CN, wherein CH3 or CH3O is optionally substituted with from 1 to 3 halogens; Q2 is N or CH; R3 is H, F, CH3, CH3O, CHF2, CH2F, CF3, CHF2O, CH2FO or CF3O; R4, R5, R6 and R7 are each independently H, C1-4alkyl or C1-4haloalkyl; Y1 is N or CR9, wherein R9 is H, C1-4alkyl or C1-4haloalkyl; Y2 is N or CR10; wherein R10 and R11 are each independently optionally substituted C1-4alkyl, C1-4haloalkyl, optionally substituted C3-6cycloalkyl, optionally substituted aryl or optionally substituted heteroaryl, wherein two adjacent substituents on an aryl or heteroaryl ring are optionally taken together with the atoms to which they attach to form an optionally substituted fused 5- or 6-membered ring having from 0-2 heteroatoms selected from O, N or S; and (i) R1 is optionally substituted aryl or optionally substituted heteroaryl; and R8 is H, C1-4alkyl or C1-4haloalkyl; or (ii) R1 is optionally substituted C1-6alkyl; and R8 is C1-4alkyl or C1-4haloalkyl.