Structure-Based Discovery of a Series of 5H-Pyrrolo[2,3-b]pyrazine FGFR Kinase Inhibitors

doi:10.3390/molecules23030698

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	Structure-Based Discovery of a Series of 5H-Pyrrolo[2,3-b]pyrazine FGFR Kinase Inhibitors
	Jiang, Alan 1,2; Liu, Qiufeng 3; Wang, Ruifeng 4,5; Wei, Peng 4,5; Dai, Yang 2; Wang, Xin5 ; Xu, Yechun3 ; Ma, Yuchi 5; Ai, Jing2 ; Shen, Jingkang 5
刊名	MOLECULES
	2018-03
卷号	23 期号:3
关键词	cancer FGFR kinase inhibitor pyrrolo[2,3-b]pyrazine
ISSN号	1420-3049
DOI	10.3390/molecules23030698
文献子类	Article
英文摘要	Fibroblast growth factor receptors (FGFRs), a subfamily of receptor tyrosine kinases, are aberrant in various cancer types, and considered to be promising targets for cancer therapy. We started with a weak-active compound that was identified from our internal hepatocyte growth factor receptor (also called c-Met) inhibitor project, and optimized it with the guidance of a co-crystal structure of compound 8 with FGFR1. Through rational design, synthesis, and the biological evaluation of a series of 5H-pyrrolo[2,3-b]pyrazine derivatives, we discovered several potent FGFR kinase inhibitors. Among them, compound 13 displayed high selectivity and favorable metabolic properties, demonstrating a promising lead for further development.
资助项目	National Natural Science Foundation of China[81661148046] ; National Natural Science Foundation of China[81773762] ; Personalized Medicines Molecular Signature-based Drug Discovery and Development[00000000] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020317]
WOS关键词	GROWTH-FACTOR RECEPTORS ; CH5183284/DEBIO 1347 ; SELECTIVE INHIBITOR ; TARGETING FGFR ; CANCER ; POTENT ; FAMILY ; AZD4547 ; MODELS ; LUNG
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI
WOS记录号	WOS:000428514100189
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279862]
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发现与设计中心药物化学研究室
通讯作者	Xu, Yechun; Ma, Yuchi; Ai, Jing; Xiong, Bing
作者单位	1.Nanchang Univ, Coll Pharm, 461 Bayi Ave, Nanchang 330006, Jiangxi, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Design & Discovery Ctr, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 4.Shenyang Pharmaceut Univ, Minist Educ, Key Lab Struct Based Drug Design & Discovery, Shenyang 110016, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Jiang, Alan,Liu, Qiufeng,Wang, Ruifeng,et al. Structure-Based Discovery of a Series of 5H-Pyrrolo[2,3-b]pyrazine FGFR Kinase Inhibitors[J]. MOLECULES,2018,23(3).
APA	Jiang, Alan.,Liu, Qiufeng.,Wang, Ruifeng.,Wei, Peng.,Dai, Yang.,...&Xiong, Bing.(2018).Structure-Based Discovery of a Series of 5H-Pyrrolo[2,3-b]pyrazine FGFR Kinase Inhibitors.MOLECULES,23(3).
MLA	Jiang, Alan,et al."Structure-Based Discovery of a Series of 5H-Pyrrolo[2,3-b]pyrazine FGFR Kinase Inhibitors".MOLECULES 23.3(2018).