Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have one of the following structures (I), (II) or (III): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R1, R2a, R2b, R2c, R3a, R3b, R4a, R4b, R5a, R5b, R6, A, B, G1, G2, L1, L2, m1, m2, n, x, y, X 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.本發明提供具有作為G12C突變KRAS蛋白之抑制劑之活性的化合物。該等化合物具有以下結構(I)、(II)或(III)中之一者:或其醫藥學上可接受之鹽、立體異構體或前藥,其中R1、R2a、R2b、R2c、R3a、R3b、R4a、R4b、R5a、R5b、R6、A、B、G1、G2、L1、L2、m1、m2、n、x、y、X及E如本文所定義。亦提供與此類化合物之製備及用途相關的方法、包含此類化合物之醫藥組合物及調節G12C突變KRAS蛋白之活性以治療諸如癌症之病症的方法。
