HETEROCYCLIC SPIRO COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF CANCER

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, stereoisomer, isotopic form orprodrug thereof, wherein R1, L1, L2, L3, A1, A2, A3, A4, G1, G2, E, W, X, Y, Z, m, and n 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. 本申请提供具有作为G12C突变KRAS蛋白的抑制剂的活性的化合物。所述化合物具有以下结构(I)：或其药物可接受的盐、立体异构体、同位素形式或前药，其中R1、L1、L2、L3、A1、A2、A3、A4、G1、G2、E、W、X、Y、Z、m和n如本文所定义。还提供了与此类化合物的制备和应用相关的方法、包含此类化合物的药物组合物以及调节G12C突变KRAS蛋白的活性以治疗诸如癌症的病症的方法。