A structure-guided optimization of pyrido[2,3-d]pyrimidin-7-ones as selective inhibitors of EGFRL858R/T790M mutant with improved pharmacokinetic properties

Structural optimization of pyrido[2,3-d]pyrimidin-7-ones yielded new selective EGFRT790M inhibitors. Compound 9s exhibited good pharmacokinetic properties with F value of 16%, and inhibited EGFRL858R/T790M kinase and H1975 cells with IC50 values of 2.0 and 40 nM, respectively.191