Synthesis and biological evaluation of new series of quinazoline derivatives as EGFR/HER2 dual-target inhibitors

Xiaoyu Jiao; Qing Zhang; Yue Zhang; Junlan Shao; Lei Ding; Chunlei Tang; Bainian Feng

doi:10.1016/j.bmcl.2022.128703

Synthesis and biological evaluation of new series of quinazoline derivatives as EGFR/HER2 dual-target inhibitors

Bioorg Med Chem Lett. 2022 Jul 1:67:128703. doi: 10.1016/j.bmcl.2022.128703. Epub 2022 Mar 29.

Authors

Xiaoyu Jiao¹, Qing Zhang¹, Yue Zhang¹, Junlan Shao¹, Lei Ding¹, Chunlei Tang², Bainian Feng³

Affiliations

¹ School of Pharmaceutical Science, Jiangnan University, Wuxi, China.
² School of Pharmaceutical Science, Jiangnan University, Wuxi, China. Electronic address: tangcl@jiangnan.edu.cn.
³ School of Pharmaceutical Science, Jiangnan University, Wuxi, China. Electronic address: fengbainian@jiangnan.edu.cn.

PMID: 35364239
DOI: 10.1016/j.bmcl.2022.128703

Abstract

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 IC₅₀ = 0.30 nM, HER2 IC₅₀ = 6.07 nM, NCI-H358 GI₅₀ = 23.30 nM, PC-9 GI₅₀ = 1.95 nM, Calu-3 GI₅₀ = 23.13 nM NCI-H1781 GI₅₀ = 41.61 nM).

Keywords: Drug resistance; EGFR/HER2 Dual-target inhibitors; Quinazoline.

MeSH terms

Antineoplastic Agents* / pharmacology
Cell Line, Tumor
Cell Proliferation
Drug Screening Assays, Antitumor
ErbB Receptors / metabolism
Protein Kinase Inhibitors / pharmacology
Quinazolines* / pharmacology
Structure-Activity Relationship

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
Quinazolines
ErbB Receptors