A structure-guided optimization of pyrido[2,3-d]pyrimidin-7-ones as selective inhibitors of EGFRL858R/T790M mutant with improved pharmacokinetic properties
Optimization of pyrido[2,3-d]pyrimidin-7-ones with improved pharmacokinetic properties. Compound 9s potently suppressed EGFRL858R/T790M kinase and H1975 cells. Compound 9s exhibited moderate plasma exposure and an oral bioavailability value of 16%.