Design, synthesis and biological evaluation of phosphoroxy quinazoline derivatives as potential EGFRT790M/C797S inhibitors

Brigatinib was used as the lead compound to modify its structure to obtain a series of derivatives with a skeleton of phosphoroxy quinazoline. Among them, compound 8a showed excellent inhibitory activity against C797S mutant EGFR enzyme and cancer cells. Significantly, 8a presented acceptable pharmacokinetic parameters and exhibited potent antitumor activity in vivo.