Design, Synthesis, Biological Evaluation and Docking Study of Novel Quinazoline Derivatives As EGFR-TK Inhibitors

Abstract

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.

Graphical Abstract

Keywords: :

• antiproliferative
• benzazepine
• EGFR inhibitors
• quinazoline

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Financial & competing interests disclosure

This research was supported by the Science and Technology Program of Zhejiang Province (Key Innovative Team) under grant no. KYY-ZX-20190351, and Zhejiang Provincial Natural Science Foundation of China under grant no. LY19B020008. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.