College of Pharmaceutical Science, Zhejiang University of Technology & Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Hangzhou 310014, PR China.
Luoxi Medical Technology (Hangzhou) Co., Ltd., Hangzhou 310018, PR China.
Future Med Chem. 2021 Apr;13(7):601-612. doi: 10.4155/fmc-2020-0015. Epub 2021 Mar 9.
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.
喹唑啉类化合物在癌症治疗方面已被证明多年来具有疗效。本研究整合了几种 EGFR 抑制剂的结构特征，并构建了 4-位带有苯并氮杂卓部分的喹唑啉类化合物。大多数化合物表现出优异的抗肿瘤活性。化合物 33e 对四种测试细胞系表现出优异的抗肿瘤活性（IC：1.06-3.55 μM）。随后进行了 33e 的酶、信号通路和凋亡检测，以研究其作用机制。本研究筛选出 4-位带有苯并氮杂卓部分的化合物 33e，为 EGFR-T790M 抑制剂的设计提供了有价值的信息，值得进一步研究。
