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, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z 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G12C突變型KRAS蛋白質之抑制劑活性的化合物。該等化合物具有以下結構(I)：或其醫藥學上可接受之鹽、互變異構體、前藥或立體異構體，其中R1、R2a、R3a、R3b、R4a、R4b、G1、G2、L1、L2、m1、m2、A、B、W、X、Y、Z及E如本文所定義。亦提供與此等化合物之製備及用途相關的方法、包含此等化合物的醫藥組合物及調節G12C突變型KRAS蛋白質活性以供治療諸如癌症之病症的方法。
