Design, Synthesis and Biological Evaluation of 6-(2,6-Dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors

doi:10.3390/molecules21101407

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	Design, Synthesis and Biological Evaluation of 6-(2,6-Dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors
	Zhang, Zhen 1,2; Zhao, Dongmei 1; Dai, Yang 3; Cheng, Maosheng 1; Geng, Meiyu3 ; Shen, Jingkang 2; Ma, Yuchi 2; Ai, Jing3 ; Xiong, Bing2
刊名	MOLECULES
	2016-10
卷号	21 期号:10
关键词	cancer FGFR inhibitor 4-substituted-1H-indazole
ISSN号	1420-3049
DOI	10.3390/molecules21101407
文献子类	Article
英文摘要	Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a newseries of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazole derivatives as potent FGFR inhibitors. The compound 6-(2,6-dichloro-3,5-dimethoxyphenyl)-N-phenyl-1H-indazole-4-carboxamide (10a) was identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that 6-(2,6-dichloro-3,5-dimethoxyphenyl)N-(3-(4-methylpiperazin-1-yl) phenyl)-1H-indazole-4-carboxamide (13a) is the most potent FGFR1 inhibitor in this series, with an enzyme inhibitory activity IC50 value of about 30.2 nM.
资助项目	Foundation of China Postdoctoral Science Grant[2015M580370] ; National Natural Science Foundation of China[81473243] ; Youth Innovation Promotion Association[00000000] ; "Personalized Medicines-Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020317] ; program for Innovative Research Team of the Ministry of Education[00000000] ; Program for Liaoning Innovative Research Team in University[00000000]
WOS关键词	SELECTIVE INHIBITOR ; TYROSINE KINASE ; LUNG-CANCER ; FGFR ; FAMILY ; ANGIOGENESIS ; GLIOBLASTOMA ; MANAGEMENT ; DISCOVERY
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI AG
WOS记录号	WOS:000389917900144
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275868]
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药物化学研究室
通讯作者	Zhao, Dongmei; Ma, Yuchi; Ai, Jing; Xiong, Bing
作者单位	1.Shenyang Pharmaceut Univ, Minist Educ, Key Lab Struct Based Drug Design & Discovery, Shenyang 110016, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Dept Med Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Zhen,Zhao, Dongmei,Dai, Yang,et al. Design, Synthesis and Biological Evaluation of 6-(2,6-Dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors[J]. MOLECULES,2016,21(10).
APA	Zhang, Zhen.,Zhao, Dongmei.,Dai, Yang.,Cheng, Maosheng.,Geng, Meiyu.,...&Xiong, Bing.(2016).Design, Synthesis and Biological Evaluation of 6-(2,6-Dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors.MOLECULES,21(10).
MLA	Zhang, Zhen,et al."Design, Synthesis and Biological Evaluation of 6-(2,6-Dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors".MOLECULES 21.10(2016).