Design, synthesis and bioactivity evaluation of novel quinazoline based KRASG12C inhibitors

Abstract

KRAS is a member of the RAS gene family, which is involved in the regulation of human life activities. KRAS^G12C mutation is distributed in many tumors and has been the focus of attention. In our study, we analyzed the binding of BAY-293 to KRAS protein using molecular docking technology. We designed and synthesized 20 compounds and tested their bioactivity. At the same time, we found that compound 8P (IC₅₀ = 2.6 ± 1.2 μM) had good inhibitory activity against the A549 cell line and compound 8e had a good inhibitory effect on the McF-7 cell line with IC₅₀ = 5.5 ± 0.3 μM.