Optimization of 1H-indazol-3-amine derivatives as potent fibroblast growth factor receptor inhibitors

doi:10.1016/j.bmcl.2017.06.068

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	Optimization of 1H-indazol-3-amine derivatives as potent fibroblast growth factor receptor inhibitors
	Cui, Jing 1; Peng, Xia 2; Gao, Dingding 1; Dai, Yang 2; Ai, Jing2 ; Li, Yingxia 1
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2017-08-15
卷号	27 期号:16 页码:3782-3786
关键词	FGFR Inhibitors Cellular activity Fluorine
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2017.06.068
文献子类	Article
英文摘要	Fibroblast growth factor receptor (FGFR) is a potential target for cancer therapy because of its critical role in promoting cancer formation and progression. In a continuing effort to improve the cellular activity of hit compound 7r bearing an indazole scaffold, which was previously discovered by our group, several compounds harnessing fluorine substituents were designed, synthesized and biological evaluated. Besides, the region extended out to the ATP binding pocket toward solvent was also explored. Among them, compound 2a containing 2,6-difluoro-3-methoxyphenyl residue exhibited the most potent activities (FGFR1: less than 4.1 nM, FGFR2: 2.0 +/- 0.8 nM). More importantly, compound 2a showed an improved antiproliferative effect against KG1 cell lines and SNU16 cell lines with IC50 values of 25.3 +/- 4.6 nM and 77.4 +/- 6.2 nM respectively. (C) 2017 Published by Elsevier Ltd.
资助项目	National Natural Science Foundation of China[81473075] ; National Natural Science Foundation of China[81473243] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development[00000000] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020103]
WOS关键词	TUMOR XENOGRAFT MODELS ; SELECTIVE INHIBITOR ; THERAPEUTIC TARGETS ; TYROSINE KINASE ; CANCER ; FLUORINE ; DESIGN ; AZD4547 ; FAMILY ; ROLES
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000407532900031
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272529]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ai, Jing; Li, Yingxia
作者单位	1.Fudan Univ, Sch Pharm, 826 Zhangheng Rd, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Cui, Jing,Peng, Xia,Gao, Dingding,et al. Optimization of 1H-indazol-3-amine derivatives as potent fibroblast growth factor receptor inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2017,27(16):3782-3786.
APA	Cui, Jing,Peng, Xia,Gao, Dingding,Dai, Yang,Ai, Jing,&Li, Yingxia.(2017).Optimization of 1H-indazol-3-amine derivatives as potent fibroblast growth factor receptor inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,27(16),3782-3786.
MLA	Cui, Jing,et al."Optimization of 1H-indazol-3-amine derivatives as potent fibroblast growth factor receptor inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 27.16(2017):3782-3786.