阅读说明：本技术 喹唑啉衍生物作为突变kras、hras或nras的调节剂 (Quinazoline derivatives as modulators of mutated KRAS, HRAS or NRAS ) 是由 李连升 冯军 吴涛 刘源 王祎 任平达 刘毅 于 2018-05-24 设计创作，主要内容包括：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)：<Image he="547" wi="568" file="DDA0002286575950000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>或其药物可接受的盐、立体异构体、同位素形式或前药,其中R<Sup>1</Sup>、R<Sup>2a</Sup>、R<Sup>2b</Sup>、R<Sup>2c</Sup>、R<Sup>3a</Sup>、R<Sup>3b</Sup>、R<Sup>4a</Sup>、R<Sup>4b</Sup>、R<Sup>5</Sup>、L<Sup>1</Sup>、L<Sup>2</Sup>、E、m<Sup>1</Sup>和m<Sup>2</Sup>如本文所定义。本申请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。(The present application provides compounds having activity as inhibitors of G12C mutant KRAS protein. The compounds have the following structure (I): or a pharmaceutically acceptable salt, stereoisomer, isotopic form or prodrug thereof, wherein R is 1 、R 2a 、R 2b 、R 2c 、R 3a 、R 3b 、R 4a 、R 4b 、R 5 、L 1 、L 2 、E、m 1 And m 2 As defined herein. Methods associated with the preparation and use of such compounds, pharmaceutical compositions comprising such compounds, and methods of modulating the activity of G12C mutant KRAS protein to treat disorders such as cancer are also provided.)