新型喹唑啉衍生物的合成及作为 EGFR/HER2 双靶抑制剂的生物评价。
Synthesis and biological evaluation of new series of quinazoline derivatives as EGFR/HER2 dual-target inhibitors.
机构信息
School of Pharmaceutical Science, Jiangnan University, Wuxi, China.
School of Pharmaceutical Science, Jiangnan University, Wuxi, China.
出版信息
Bioorg Med Chem Lett. 2022 Jul 1;67:128703. doi: 10.1016/j.bmcl.2022.128703. Epub 2022 Mar 29.
It is generally believed that EGFR/HER2 dual-target inhibitors may overcome the resistance of EGFR TKIs caused by HER2 overexpression. The structure-based synthesis and biological evaluation of quinazoline derivatives as EGFR/HER2 dual-target inhibitors has been studied in this paper. II-1, II-2, III-3, III-4 displayed comparable inhibitory potency against EGFR and HER2 and II-1 showed remarkable antiproliferative activities against NCI-H358/PC-9/Calu-3/NCI-H1781 (EGFR IC = 0.30 nM, HER2 IC = 6.07 nM, NCI-H358 GI = 23.30 nM, PC-9 GI = 1.95 nM, Calu-3 GI = 23.13 nM NCI-H1781 GI = 41.61 nM).
一般认为，EGFR/HER2 双靶抑制剂可能克服由 HER2 过表达引起的 EGFR TKI 耐药性。本文研究了基于结构的喹唑啉衍生物作为 EGFR/HER2 双靶抑制剂的合成和生物学评价。化合物 II-1、II-2、III-3、III-4 对 EGFR 和 HER2 具有相当的抑制活性，化合物 II-1 对 NCI-H358/PC-9/Calu-3/NCI-H1781 具有显著的增殖抑制活性（EGFR IC = 0.30 nM，HER2 IC = 6.07 nM，NCI-H358 GI = 23.30 nM，PC-9 GI = 1.95 nM，Calu-3 GI = 23.13 nM，NCI-H1781 GI = 41.61 nM）。
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