Design, synthesis, biological evaluation and docking study of novel quinazoline derivatives as EGFR-TK inhibitors.

Quinazoline-based compounds have been proved effective in the treatment of cancers for years. The structural features of several inhibitors of EGFR were integrated and quinazolines with a benzazepine moiety at the 4-position were constructed. Most of the compounds exhibited excellent antitumor activities. Compound 33e showed excellent antitumor activities against the four tested cell lines (IC: 1.06-3.55 μM). The enzymatic, signaling pathways and apoptosis assay of 33e were subsequently carried out to study the action of the mechanism. Compound 33e with a benzazepine moiety at the 4-position can be screened in this study and provides useful information for the design of EGFR-T790M inhibitors, which deserve additional research.