申请人:Araxes Pharma LLC
公开号:US20160108019A1
公开(公告)日:2016-04-21
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):
or a pharmaceutically acceptable salt, tautomer, stereoisomer or prodrug thereof, wherein R
1
, R
2
, R
3a
, R
3b
, R
4a
, R
4b
, G
1
, G
2
, L, m
1
, m
2
and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
提供了作为G12C突变KRAS蛋白抑制剂活性的化合物。该化合物具有以下结构(I):或其药学上可接受的盐、互变异构体、立体异构体或前药,其中R1、R2、R3a、R3b、R4a、R4b、G1、G2、L、m1、m2和E的定义如本文所述。还提供了与制备和使用这种化合物相关的方法,包括包含这种化合物的制药组合物以及用于治疗癌症等疾病的调节G12C突变KRAS蛋白活性的方法。