Discovery of 1,3-Diaryl-pyridones as Potent VEGFR-2 Inhibitors: Design, Synthesis, and Biological Evaluation
文献类型：期刊论文
| 作者 | Yan, Wei2; Huang, Zhaoru3,4; Wang, Zhengyu5; Cao, Sufen2; Tong, Linjiang3; Zhang, Tao3; Wang, Chen1; Zhou, Lin4; Ding, Jian3 ; Luo, Cheng1
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| 刊名 | CHEMICAL BIOLOGY & DRUG DESIGN
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| 出版日期 | 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. |
| WOS关键词 | TYROSINE KINASE INHIBITOR ; TUMOR ANGIOGENESIS ; DERIVATIVES ; CANCER ; NAPHTHAMIDES ; MECHANISMS ; RECEPTORS ; FLT3 |
| 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研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000374031500006 |
| 出版者 | WILEY-BLACKWELL |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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