Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):(I) or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R1, R2a, R2b, R2c, R3a, R3b, R4a, R4b, R5a, R5b, R6, A, G1, G2, L1, L2, m1, m2, n, X and E are as defined herein, and wherein at least one of R3a, R3b, R4aor R4bis not H. 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突變型KRAS蛋白質之抑制劑之活性的化合物。該等化合物具有以下結構(I)：(I) 或其醫藥上可接受之鹽、立體異構體或前藥，其中R1、R2a、R2b、R2c、R3a、R3b、R4a、R4b、R5a、R5b、R6、A、G1、G2、L1、L2、m1、m2、n、X及E係如本文所定義，且其中R3a、R3b、R4a或R4b中之至少一者不為H。本發明亦提供與該等化合物之製備及使用相關的方法、包含該等化合物之醫藥組合物及調節G12C突變型KRAS蛋白質之活性以便治療病症(諸如癌症)的方法。
