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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

文献类型：期刊论文

作者Zhang, Zhen1,2; Zhao, Dongmei1; Dai, Yang3; Cheng, Maosheng1; Geng, Meiyu3; Shen, Jingkang2; Ma, Yuchi2; Ai, Jing3; Xiong, Bing2
刊名MOLECULES
出版日期2016-10
卷号21期号:10
关键词cancer FGFR inhibitor 4-substituted-1H-indazole
ISSN号1420-3049
DOI10.3390/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.
WOS关键词SELECTIVE INHIBITOR ; TYROSINE KINASE ; LUNG-CANCER ; FGFR ; FAMILY ; ANGIOGENESIS ; GLIOBLASTOMA ; MANAGEMENT ; DISCOVERY
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研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:000389917900144
出版者MDPI AG
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).

入库方式： OAI收割

来源：上海药物研究所

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