Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: Synthesis and SAR study as tyrosine kinase c-Met inhibitors

doi:10.1016/j.bmcl.2012.08.075

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	Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: Synthesis and SAR study as tyrosine kinase c-Met inhibitors
	Wu, Kui 2; Ai, Jing3 ; Liu, Qiufeng 1; Chen, TianTian 1; Zhao, Ailing 4; Peng, Xia 3; Wang, Yuanxiang 4; Ji, Yinchun 3; Yao, Qizheng 2; Xu, Yechun1
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2012-10-15
卷号	22 期号:20 页码:6368-6372
关键词	c-Met kinase 3,5-Diamino-7-trifluoroquinoline hERG Antitumor activity Structure-activity relationship (SAR)
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2012.08.075
文献子类	Article
英文摘要	Two series of new analogues were designed by replacing the quinoline scaffold of our earlier lead 2 (zgw-atinib) with quinoxaline and pyrido[2,3-d]pyrimidine frameworks. Moderate c-Met inhibitory activity was observed in the quinoxaline series. Among the pyrido[2,3-d]pyrimidine series, compounds 13a-c possessing an O-linkage were inactive, whilst the N-linked analogues 15a-c retained c-Met inhibitory potency. Highest activity was observed in the 3-nitrobenzyl analog 15b that showed an IC50 value of 6.5 nM. Further structural modifications based on this compound were undergoing. (c) 2012 Elsevier Ltd. All rights reserved.
资助项目	Chinese National Science Foundation for the Distinguished Young Scholars Program[81125021] ; Chinese National Science Foundation for the Innovation Research Group[810 21062] ; National Science & Technology Major Project on Key New Drug Creation and Manufacturing Program[2012ZX09103-101-035] ; National Science & Technology Major Project on Key New Drug Creation and Manufacturing Program[2010ZX09401-401] ; National Science & Technology Major Project on Key New Drug Creation and Manufacturing Program[2012ZX093010 01-007] ; Shanghai Commission of Science and Technology[10JC1417100] ; Shanghai Commission of Science and Technology[10dz1910104] ; Hundred Talents Project of Chinese Academy of Sciences[00000000] ; National Natural Science Foundation of China[81102461] ; National Program on Key Basic Research Project of China[2012CB910704]
WOS关键词	FACTOR SCATTER FACTOR ; GROWTH ; METASTASIS ; PHENOTYPE ; CANCER ; POTENT ; CELLS
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000309609500011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277910]
专题	药物发现与设计中心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药理学第一研究室
通讯作者	Yao, Qizheng
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; 2.China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Synthet Organ & Med Chem Lab, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wu, Kui,Ai, Jing,Liu, Qiufeng,et al. Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: Synthesis and SAR study as tyrosine kinase c-Met inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2012,22(20):6368-6372.
APA	Wu, Kui.,Ai, Jing.,Liu, Qiufeng.,Chen, TianTian.,Zhao, Ailing.,...&Zhang, Ao.(2012).Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: Synthesis and SAR study as tyrosine kinase c-Met inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,22(20),6368-6372.
MLA	Wu, Kui,et al."Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: Synthesis and SAR study as tyrosine kinase c-Met inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 22.20(2012):6368-6372.