Synthesis and biological evaluation of 2-amino-5-aryl-3-benzylthiopyridine scaffold based potent c-Met inhibitors
文献类型：期刊论文
| 作者 | Zhang, Dengyou1; Zhang, Xiaowei3; Ai, Jing3 ; Zhai, Yun1; Liang, Zhongjie1; Wang, Ying3; Chen, Yi3; Li, Chunpu1; Zhao, Fei1; Jiang, Hualiang1,2
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
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| 出版日期 | 2013-11-01 |
| 卷号 | 21期号:21页码:6804-6820 |
| 关键词 | Receptor tyrosine kinase c-Met 2-Amino-5-aryl-3-benzylthiopyridine |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2013.07.032 |
| 文献子类 | Article |
| 英文摘要 | A series of 2-amino-N-benzylpyridine-3-carboxnamides, 2-amino-N-benzylpyridine-3-sulfonamides and 2-amino-3-benzylthiopyridines against c-Met were designed by means of bioisosteric replacement and docking analysis. Optimization of the 2-amino-3-benzylthiopyridine scaffold led to the identification of compound (R)-10b displaying c-Met inhibition with an IC50 up to 7.7 nM. In the cytotoxic evaluation, compound (R)-10b effectively inhibited the proliferation of c-Met addictive human cancer cell lines (IC50 from 0.19 to 0.71 mu M) and c-Met activation-mediated cell metastasis. At a dose of 100 mg/Kg, (R)-10b evidently inhibited tumor growth (45%) in NIH-3T3/TPR-Met xenograft model. Of note, (R)-10b could overcome c-Met-activation mediated gefitinib-resistance, which indicated its potential use for drug combination. Taken together, 2-amino-3-benzylthiopyridine scaffold was first disclosed and exhibited promising pharmacological profiles against c-Met, which left room for further exploration. (C) 2013 Elsevier Ltd. All rights reserved. |
| WOS关键词 | HEPATOCYTE GROWTH-FACTOR ; KINASE INHIBITORS ; LUNG-CANCER ; GEFITINIB RESISTANCE ; MONOCLONAL-ANTIBODY ; TUMOR-GROWTH ; IN-VIVO ; DISCOVERY ; ANTAGONISTS ; IDENTIFICATION |
| 资助项目 | National Basic Research Program of China[2009CB940903] ; National Basic Research Program of China[2012CB518000] ; National Natural Science Foundation of China[20721003] ; National Natural Science Foundation of China[81025017] ; National S&T Major Projects[2012ZX09103-101-072] ; National S&T Silver Project[260644] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2012ZX09301001-007] ; National Program on Key Basic Research Project of China[2012CB910704] ; Natural Science Foundation of China for Innovation Research Group[81021062] ; National Natural Science Foundation[81102461] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000325164500059 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277410]  |
| 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 | Geng, Meiyu |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Drug Res, CAS Key Lab Receptor Res, Shanghai Inst Mat Med,Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Dengyou,Zhang, Xiaowei,Ai, Jing,et al. Synthesis and biological evaluation of 2-amino-5-aryl-3-benzylthiopyridine scaffold based potent c-Met inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2013,21(21):6804-6820. |
| APA | Zhang, Dengyou.,Zhang, Xiaowei.,Ai, Jing.,Zhai, Yun.,Liang, Zhongjie.,...&Liu, Hong.(2013).Synthesis and biological evaluation of 2-amino-5-aryl-3-benzylthiopyridine scaffold based potent c-Met inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY,21(21),6804-6820. |
| MLA | Zhang, Dengyou,et al."Synthesis and biological evaluation of 2-amino-5-aryl-3-benzylthiopyridine scaffold based potent c-Met inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY 21.21(2013):6804-6820. |
入库方式： OAI收割
来源：上海药物研究所
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