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Discovery of N-(3-bromo-1H-indol-5-yl)-quinazolin-4-amine as an effective molecular skeleton to develop reversible/irreversible pan-HER inhibitors

文献类型：期刊论文

作者Tang, Qidong5; Peng, Ting4; Hu, Jie5; Zhang, Tao4; Chen, Pengqin3,5; Chen, Daoxing5; Wang, Yunjie5; Chen, Lingfeng2; Tong, Linjiang4; Chen, Yi4
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2022-04-05
卷号233页码:13
关键词Reversible irreversible pan-HER inhibitor Quinazolin-4-amine derivatives Anti-tumor Structure-activity relationship
ISSN号0223-5234
DOI10.1016/j.ejmech.2022.114249
通讯作者Xie, Hua(hxie@simm.ac.cn) ; Liang, Guang(wzmcliangguang@163.com)
英文摘要Pan-HER inhibitors exhibit extensive biological activity and offer unique advantages and usually bind to targets in an irreversible manner. Owing to the off-target toxicity of irreversible inhibitors, reversible pan-HER inhibitors are desirable. Herein, we describe the process of N-(ring structure fused phenyl) quinazoline-4-amine-based design, synthesis, and biological evaluation of pan-HER inhibitors in vitro and in vivo. Compound C5, with the molecular skeleton of N-(3-bromo-1H-indol-5-yl)-quinazolin-4-amine, displayed irreversible binding just like other effective pan-HER inhibitors. To our surprise, compound C6, which possessed the same skeleton, was found to be a high-strength reversible pan-HER inhibitor. This compound was capable of inhibiting HER1s (such as EGFR T790M/L858R and WT), HER2, and HER4 and can be considered as a breakthrough in the development of pan-HER inhibitors. Altogether, N-(3-bromo-1H-indol-5-yl)-quinazolin-4-amine can serve as an effective molecular skeleton for developing both reversible and irreversible pan-HER inhibitors in the following discovery of antitumor drugs. (c) 2022 Elsevier Masson SAS. All rights reserved.
WOS关键词CELL LUNG-CANCER ; EGFR ; FAMILY
资助项目National Key Research Project[2017YFA0506000] ; National Natural Science Foundation of China[81930108] ; National Natural Science Foundation of China[81903638] ; Wenzhou Science and Technology Key Project[2018ZY009] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020112]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000793270500002
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/300995]  
专题新药研究国家重点实验室
通讯作者Xie, Hua; Liang, Guang
作者单位1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
2.Hangzhou Med Coll, Sch Pharm, Hangzhou 311399, Peoples R China
3.Univ Chinese Acad Sci, Wenzhou Inst, Wenzhou 325001, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Wenzhou Med Univ, Chem Biol Res Ctr, Sch Pharmaceut Sci, Wenzhou 325035, Peoples R China
推荐引用方式
GB/T 7714		 Tang, Qidong,Peng, Ting,Hu, Jie,et al. Discovery of N-(3-bromo-1H-indol-5-yl)-quinazolin-4-amine as an effective molecular skeleton to develop reversible/irreversible pan-HER inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2022,233:13.
APA Tang, Qidong.,Peng, Ting.,Hu, Jie.,Zhang, Tao.,Chen, Pengqin.,...&Liang, Guang.(2022).Discovery of N-(3-bromo-1H-indol-5-yl)-quinazolin-4-amine as an effective molecular skeleton to develop reversible/irreversible pan-HER inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,233,13.
MLA Tang, Qidong,et al."Discovery of N-(3-bromo-1H-indol-5-yl)-quinazolin-4-amine as an effective molecular skeleton to develop reversible/irreversible pan-HER inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 233(2022):13.

入库方式： OAI收割

来源：上海药物研究所

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