RAF kinase modulator compounds and methods of use thereof

摘要

Compounds, compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases.

主权项

1. A compound having formula XVII: or a pharmaceutically acceptable salt thereof, wherein X is O or S; R1a and R1b are selected as follows: i) R1a and R1b are each independently alkoxy, alkoxyalkoxy, alkylsulfonylalkoxy or a group of formula: where K is a direct bond or alkylene, optionally substituted with a hydroxy group; A is N or CH; Y is —O, —S(O)2, —N(R14) or —C(H)R15; p is 0 or 1; R14 is hydrogen, alkyl, haloalkyl, hydroxyalkyl or S(O)tR13; R15 is hydrogen, halo, alkyl, hydroxyalkyl or —OR12; t is 1 or 2; R12 is hydrogen or alkyl; and R13 is alkyl; or ii) R1a and R1b groups together form an alkylenedioxy group; and R10 is hydrogen, halo, alkyl, aryl, heterocyclyl, heteroaryl, cycloalkyl or cycloalkylalkyl; where alkyl, aryl, heterocyclyl and heteroaryl groups are optionally substituted with 1-3 groups selected from halo, cyano, hydroxyl and alkoxy.