Design, synthesis and biological evaluation of pyrazolylaminoquinazoline derivatives as highly potent pan-fibroblast growth factor receptor inhibitors

doi:10.1016/j.bmcl.2016.04.028

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	Design, synthesis and biological evaluation of pyrazolylaminoquinazoline derivatives as highly potent pan-fibroblast growth factor receptor inhibitors
	Fan, Jun 2; Dai, Yang 3; Shao, Jingwei 2; Peng, Xia 3; Wang, Chen 1; Cao, Sufen 4; Zhao, Bin 2; Ai, Jing3 ; Geng, Meiyu3 ; Duan, Wenhu2
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2016-06-01
卷号	26 期号:11 页码:2594-2599
关键词	Antitumor FGFR inhibitor Pyrazolylaminoquinazoline
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2016.04.028
文献子类	Article
英文摘要	Fibroblast growth factor receptors (FGFRs) are important oncology targets due to the dysregulation of this signaling pathway in a wide variety of human cancers. We identified a series of pyrazolylaminoquinazoline derivatives as potent FGFR inhibitors with low nanomolar potency. The representative compound 29 strongly inhibited FGFR1-3 kinase activity and suppressed FGFR signaling transduction in FGFR-addicted cancer cells; FGFRs-driven cell proliferation was also strongly inhibited regardless of mechanistic complexity implicated in FGFR activation, which further confirmed that 29 was a potent pan-FGFR inhibitor. The flexibility of our structure offered the potential to preserve good affinity for mutant FGFR, which is important for developing TKIs with long-term efficacy. (C) 2016 Elsevier Ltd. All rights reserved.
资助项目	National Natural Science Foundation of China[81273365] ; National Natural Science Foundation of China[81573271] ; National Natural Science Foundation of China[81473243] ; National Natural Science Foundation of China[81321092] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China[2014ZX09304002-008-001] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China[2012ZX09301001-007] ; Shanghai Science and Technology Commission[1315431901300] ; SA-SIBS Scholarship Program[00000000]
WOS关键词	TYROSINE KINASE ; SELECTIVE INHIBITOR ; FGFR INHIBITOR ; CANCER ; DISCOVERY ; AZD4547 ; MODELS ; FAMILY
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000374988600006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276030]
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	Ai, Jing; Geng, Meiyu; Duan, Wenhu
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 4.E China Univ Sci & Technol, Sch Pharm, 130 Mei Long Rd, Shanghai 200237, Peoples R China
推荐引用方式 GB/T 7714	Fan, Jun,Dai, Yang,Shao, Jingwei,et al. Design, synthesis and biological evaluation of pyrazolylaminoquinazoline derivatives as highly potent pan-fibroblast growth factor receptor inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2016,26(11):2594-2599.
APA	Fan, Jun.,Dai, Yang.,Shao, Jingwei.,Peng, Xia.,Wang, Chen.,...&Duan, Wenhu.(2016).Design, synthesis and biological evaluation of pyrazolylaminoquinazoline derivatives as highly potent pan-fibroblast growth factor receptor inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,26(11),2594-2599.
MLA	Fan, Jun,et al."Design, synthesis and biological evaluation of pyrazolylaminoquinazoline derivatives as highly potent pan-fibroblast growth factor receptor inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 26.11(2016):2594-2599.