化学
组合化学
废止
芳基
合理设计
异喹啉
表面改性
药物发现
脚手架
抗癌药
立体化学
药品
纳米技术
有机化学
数据库
生物化学
药理学
计算机科学
医学
烷基
材料科学
物理化学
催化作用
作者
Zi-Rong Gong,Yu Zhao,Bo Xu,Yang Zhou,Bo Ren,Haidong Yang,Chao Zeng,R. Chen,Xu Yong,Qing Li
标识
DOI:10.1016/j.bioorg.2023.106954
摘要
Developing a synthetic methodology to expediently construct a specific drug scaffold with the desired biological activity remains challenging. Herein, we describe a work on rational application of a synthetic methodology in the synthesis of KRASG12C inhibitors. Novel KRASG12C inhibitors were initially designed with 1-amino-3-aryl isoquinoline scaffold using structure-based drug design strategy. A ruthenium-catalyzed direct mono-C-H functionalization/annulation cascade reaction of amidines and sulfoxonium ylides was then developed with high versatility of substrates and good tolerance for polar functional groups. By using this reaction, the target compounds 1-amino-3-aryl isoquinolines were facilely prepared. Further in vitro tests led to identification of two novel lead compounds with KRASG12C inhibitory activity.
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