Design, synthesis and biological evaluation of novel 3,4-dihydro-2H-[1,4] oxazino [2,3-f]quinazolin derivatives as EGFR-TKIs

Starting with our previously reported work, a novel series of 3,4-dihydro-2H-[1,4]oxazino[2,3-f]quinazolin-derivatives were designed, synthesized and evaluated as potent EGFR tyrosine kinase inhibitors. All of the compounds showed significant inhibitory activities against EGFRwt kinase (IC50 <= 937.7 nM). Among them, compound 7j demonstrated the most potent inhibitory activity toward EGFRwt tyrosine kinase with IC50 value of 25.69 nM and showed good antiproliferative activities against NCI-H1563 and H1975 cells. The median cytotoxic concentration (CC50) showed that most of the tested compounds displayed almost no cytotoxicity in vitro against 16HBE cells. In view of the reported compounds activity, the structure deserves further optimization as cancer treatment agents.

Automated summary

Starting with our previously reported work, a series of novel 3,4-dihydro-2H-[1,4]oxazino[2,3-f]quinazolin-derivatives were designed, synthesized, and evaluated as potent EGFR tyrosine kinase inhibitors. All compounds showed significant inhibitory activities against EGFRwt kinase (IC50 <= 937.7 nM). Among them, compound 7j exhibited the most potent inhibitory activity with an IC50 value of 25.69 nM and demonstrated good antiproliferative activities against NCI-H1563 and H1975 cells. The tested compounds displayed low cytotoxicity against 16HBE cells in vitro. Based on the reported activity, further optimization of the structure is warranted as potential cancer treatment agents.