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


Jin H(1), Wu BX(2), Zheng Q(1), Hu CH(1), Tang XZ(1), Zhang W(1), Rao GW(1).
Author information:
(1)College of Pharmaceutical Science, Zhejiang University of Technology & Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Hangzhou 310014, PR China.
(2)Luoxi Medical Technology
(Hangzhou) Co., Ltd., Hangzhou 310018, PR China.


Background: Quinazoline-based compounds have been proved effective in the treatment of cancers for years. Materials & methods: The structural features of several inhibitors of EGFR were integrated and quinazolines with a benzazepine moiety at the 4-position were constructed. Results: Most of the compounds exhibited excellent antitumor activities. Compound 33e showed excellent antitumor activities against the four tested cell lines (IC50: 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. Conclusion: 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.