Discovery of 1,3-Diaryl-pyridones as Potent VEGFR-2 Inhibitors: Design, Synthesis, and Biological Evaluation

doi:10.1111/cbdd.12703

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Discovery of 1,3-Diaryl-pyridones as Potent VEGFR-2 Inhibitors: Design, Synthesis, and Biological Evaluation
	Yan, Wei 2; Huang, Zhaoru 3,4; Wang, Zhengyu 5; Cao, Sufen 2; Tong, Linjiang 3; Zhang, Tao 3; Wang, Chen 1; Zhou, Lin 4; Ding, Jian3 ; Luo, Cheng1
刊名	CHEMICAL BIOLOGY & DRUG DESIGN
	2016-05
卷号	87 期号:5 页码:694-703
关键词	1 3-Diaryl-pyridone angiogenesis anticancer agent Chan-Lam coupling VEGFR-2 inhibitors
ISSN号	1747-0277
DOI	10.1111/cbdd.12703
文献子类	Article
英文摘要	In this study, we described the design, synthesis, and biological evaluation of 1,3-diaryl-pyridones as vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. The 1,3-diaryl-pyridones were synthesized via Chan-Lam and Suzuki coupling reactions. Two representative compounds, 17 and 35h, displayed excellent enzymatic inhibitory activities, with IC50 values of 3.5 and 3.0 nm, respectively. Furthermore, compounds 17 and 35h blocked the tube formation and suppressed the VEGF-induced phosphorylation of VEGFR-2 and downstream extracellular signal-regulated kinases (Erk) in human umbilical vein endothelial cells (HUVECs) at 10 nm concentration. The docking simulation showed that compound 17 bound well into the active site of VEGFR-2 via two hydrogen bonds and hydrophobic interactions.
资助项目	National Natural Science Foundation of China[81273365] ; National Natural Science Foundation of China[81173080] ; National Natural Science Foundation of China[81321092] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2012ZX09103101-024] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2014ZX09304002-008-001] ; Chinese National Programs for High Technology Research and Development[2012AA020302] ; Shanghai Science and Technology Commission[1315431901300]
WOS关键词	TYROSINE KINASE INHIBITOR ; TUMOR ANGIOGENESIS ; DERIVATIVES ; CANCER ; NAPHTHAMIDES ; MECHANISMS ; RECEPTORS ; FLT3
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000374031500006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276064]
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	Luo, Cheng; Zhou, Jinpei; Xie, Hua; Duan, Wenhu
作者单位	1.Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China; 3.Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 4.Zhengzhou Univ, Affiliated Hosp 1, Dept Gastroenterol, Zhengzhou 450014, Henan, Peoples R China; 5.China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China; 6.Shanghai Inst Mat Med, Dept Med Chem, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Yan, Wei,Huang, Zhaoru,Wang, Zhengyu,et al. Discovery of 1,3-Diaryl-pyridones as Potent VEGFR-2 Inhibitors: Design, Synthesis, and Biological Evaluation[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2016,87(5):694-703.
APA	Yan, Wei.,Huang, Zhaoru.,Wang, Zhengyu.,Cao, Sufen.,Tong, Linjiang.,...&Duan, Wenhu.(2016).Discovery of 1,3-Diaryl-pyridones as Potent VEGFR-2 Inhibitors: Design, Synthesis, and Biological Evaluation.CHEMICAL BIOLOGY & DRUG DESIGN,87(5),694-703.
MLA	Yan, Wei,et al."Discovery of 1,3-Diaryl-pyridones as Potent VEGFR-2 Inhibitors: Design, Synthesis, and Biological Evaluation".CHEMICAL BIOLOGY & DRUG DESIGN 87.5(2016):694-703.