Design and Synthesis of 5-Aminopyrazole and 5-Aminotriazole Derivatives as Fibroblast Growth Factor Receptor Inhibitors

doi:10.6023/cjoc201503045

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	Design and Synthesis of 5-Aminopyrazole and 5-Aminotriazole Derivatives as Fibroblast Growth Factor Receptor Inhibitors
	Dong Qian 2; Peng Xia 1; Wang Wen 2; Dai Yang 1; Zhao Weili 2; Ai Jing1 ; Dong Xiaochun 2
刊名	CHINESE JOURNAL OF ORGANIC CHEMISTRY
	2015-09
卷号	35 期号:9 页码:1939-1947
关键词	5-aminopyrazole 5-amino-1,2,3-triazole FGFR inhibitors anti-tumor agent
ISSN号	0253-2786
DOI	10.6023/cjoc201503045
文献子类	Article
英文摘要	Fibroblast growth factor receptor (FGFR) is a promising therapeutic target for cancer treatment. A series of 5-aminopyrazole and 5-amino-1,2,3-triazole derivatives were designed as FGFR inhibitors based on the docking mode of Debio1347 within the FGFR kinase domain. The inhibitory effects on FGFR2 kinase and the antitumor activities against human gastric cancer SNU16 cell lines were evaluated. Furthermore, the preliminary structure-activity relationships (SAR) was discussed. The results demonstrated that several compounds present good potency against FGFR2 kinase. (2-methyl-1H-benzo [d]imidazol-6-yl)-1H-pyrazol-4-yl)-1-(1H-thieno[3,2-b]pyrrol-2-yOmethanone (8) and 1-(5-amino-1-(2-methyl-1H-benzo[d]imidazol-6-yl)-1H-1,2,3-triazol-4-yl)-1-(1H-indol-2-yl)methanone (18) were the most potent with 1050 values of 3.3 and 2.3 nmol.L-1, respectively, which are similar to that of Debio1347. Compounds 8 and 18 exhibited slightly weaker antitumor activity against SNU16 cell lines than Debio1347 with IC50 value of 77.3, 155.2 nmol.L-1, respectively.
资助项目	Specialized Research Fund for the Doctoral Program of Higher Education of China[20130071110071] ; Shanghai Municipal Science & Technology Pillar Program for Bio-pharmaceuticals[13431900102]
WOS关键词	SELECTIVE INHIBITOR ; ACTIVATING MUTATIONS ; TYROSINE KINASE ; CANCER ; POTENT ; CARCINOMA ; FAMILY ; FGFR2
WOS研究方向	Chemistry
语种	中文
CSCD记录号	CSCD:5546049
出版者	SCIENCE PRESS
WOS记录号	WOS:000364618100013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276404]
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	Dong Qian
作者单位	1.Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China 2.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Dong Qian,Peng Xia,Wang Wen,et al. Design and Synthesis of 5-Aminopyrazole and 5-Aminotriazole Derivatives as Fibroblast Growth Factor Receptor Inhibitors[J]. CHINESE JOURNAL OF ORGANIC CHEMISTRY,2015,35(9):1939-1947.
APA	Dong Qian.,Peng Xia.,Wang Wen.,Dai Yang.,Zhao Weili.,...&Dong Xiaochun.(2015).Design and Synthesis of 5-Aminopyrazole and 5-Aminotriazole Derivatives as Fibroblast Growth Factor Receptor Inhibitors.CHINESE JOURNAL OF ORGANIC CHEMISTRY,35(9),1939-1947.
MLA	Dong Qian,et al."Design and Synthesis of 5-Aminopyrazole and 5-Aminotriazole Derivatives as Fibroblast Growth Factor Receptor Inhibitors".CHINESE JOURNAL OF ORGANIC CHEMISTRY 35.9(2015):1939-1947.