KRAS is the most commonly altered oncogene of RAS family, especially G12C mutant (KRASG12C), which has been a promising drug target for many cancers. On basis bicyclic pyridopyrimidinone framework first-in-class clinical KRASG12C inhibitor AMG510, scaffold hopping strategy was conducted including F–OH cyclization approach and pyridinyl N-atom working leading to new tetracyclic analogues. Compou...