Synthesis of triazolotriazine derivatives as c-Met inhibitors

doi:10.1007/s11030-020-10067-5

	Synthesis of triazolotriazine derivatives as c-Met inhibitors
	Guo, Yuting 1,3; Peng, Xia 2; Ji, Yinchun 2; Zhang, Yitong 2,3; Ding, Jian 2,3; Zhan, Zhengsheng 1; Ai, Jing 2,3; Duan, Wenhu 1,3
刊名	MOLECULAR DIVERSITY
	2020-03-10
页码	8
关键词	Receptor tyrosine kinase c-Met Triazolotriazine SAR Cellular potency
ISSN号	1381-1991
DOI	10.1007/s11030-020-10067-5
通讯作者	Zhan, Zhengsheng(zszhan@simm.ac.cn) ; Ai, Jing(jai@simm.ac.cn) ; Duan, Wenhu(whduan@simm.ac.cn)
英文摘要	Receptor tyrosine kinase c-Met is an important antitumor drug target. Triazolotriazine analogues2-10were prepared efficiently and evaluated the enzymatic and cellular c-Met activities. Brief structure-activity relationships of triazolotriazine core and CF2-quinoline part were investigated, leading to the discovery of compound8with nanomolar enzymatic c-Met activity, and subnanomolar MKN45 and EBC-1 cellular potencies. The proposed binding model of 8 and c-Met unraveled that two canonical hydrogen bonds and a pi-pi stacking interaction formed between the inhibitor and the ATP binding site of c-Met kinase domain, which accounted for its potent c-Met activities. [GRAPHICS] .
资助项目	Shanghai Sailing Program[17YF1423300] ; Youth Innovation Promotion Association of CAS[2018324] ; National Science and Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-011-016] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020228] ; National Natural Science Foundation of China[21702220]
WOS关键词	GROWTH-FACTOR RECEPTOR ; KINASE INHIBITOR ; HIGHLY POTENT ; DISCOVERY ; IDENTIFICATION ; PROTOONCOGENE ; CABOZANTINIB ; METASTASIS ; VOLITINIB ; PATHWAY
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000562581300001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/292411]
专题	中国科学院上海药物研究所
通讯作者	Zhan, Zhengsheng; Ai, Jing; Duan, Wenhu
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Guo, Yuting,Peng, Xia,Ji, Yinchun,et al. Synthesis of triazolotriazine derivatives as c-Met inhibitors[J]. MOLECULAR DIVERSITY,2020:8.
APA	Guo, Yuting.,Peng, Xia.,Ji, Yinchun.,Zhang, Yitong.,Ding, Jian.,...&Duan, Wenhu.(2020).Synthesis of triazolotriazine derivatives as c-Met inhibitors.MOLECULAR DIVERSITY,8.
MLA	Guo, Yuting,et al."Synthesis of triazolotriazine derivatives as c-Met inhibitors".MOLECULAR DIVERSITY (2020):8.