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2,7-naphthyridinone-based MET kinase inhibitors: A promising novel scaffold for antitumor drug development

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成果类型:
期刊论文
作者:
Zhuo, Lin-Sheng;Xu, Hong-Chuang;Wang, Ming-Shu;Zhao, Xing-E;Ming, Zhi-Hui;...
通讯作者:
Huang, Wei;Yang, Guang-Fu
作者机构:
[Zhu, Xiao-Lei; Yang, Guang-Fu; Wang, Ming-Shu; Huang, Wei; Yang, GF; Zhuo, Lin-Sheng; Xu, Hong-Chuang] Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Hubei, Peoples R China.
[Ming, Zhi-Hui; Zhao, Xing-E] Jiangsu Simcere Pharmaceut Co Ltd, Jiangsu Key Lab Mol Targeted Antitumor Drug Res, Nanjing 210042, Jiangsu, Peoples R China.
通讯机构:
[Huang, W; Yang, GF] C
Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Hubei, Peoples R China.
语种:
英文
关键词:
2,7-Naphthyridone;Antitumor;In vivo efficacy;MET kinase inhibitor
期刊:
European Journal of Medicinal Chemistry
ISSN:
0223-5234
年:
2019
卷:
178
页码:
705-714
基金类别:
National Key Research and Development Program of China [2017YFA0505200]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [201502063]; Natural Science Foundation of Hubei ProvinceNatural Science Foundation of Hubei Province [2016CFB562]; self-determined research funds of CCNU from the colleges' basic research and operation of MOE [CCNU18TS009]
机构署名:
本校为第一且通讯机构
院系归属:
化学学院
摘要:
As part of our effort to develop new molecular targeted antitumor drug, a novel 2,7-naphthyridone-based MET kinase inhibitor, 8-((4-((2-amino-3-chloropyridin-4-yl)oxy)- 3-fluorophenyl)amino)-2-(4-fluorophenyl)-2,7-naphthyridin-1(2H)-one (13f), was identified. Knowledge of the binding mode of BMS-777607 in MET led to the design of new inhibitors that utilize novel 2,7-naphthyridone scaffold to conformationally restrain the key pharmacophoric groups (block C). Detailed SAR studies resulted in the discovery of a new MET inhibitor 13f, displaying f...

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