Discovery of 3H-Imidazo[4,5-b]pyridines as Potent c-Met Kinase Inhibitors: Design, Synthesis, and Biological Evaluation
文献类型：期刊论文
| 作者 | Chen, Danqi1 ; Wang, Ying2; Ma, Yuchi1; Xiong, Bing1; Ai, Jing2; Chen, Yi2; Geng, Meiyu2; Shen, Jingkang1
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| 刊名 | CHEMMEDCHEM
 |
| 出版日期 | 2012-06 |
| 卷号 | 7期号:6页码:1057-1070 |
| 关键词 | c-Met kinase inhibitors imidazolopyridines structure-activity relationships hinge binders |
| ISSN号 | 1860-7179 |
| DOI | 10.1002/cmdc.201200120 |
| 文献子类 | Article |
| 英文摘要 | To identify novel c-Met inhibitors, sequences and crystal structures of the human kinome were analyzed to find interesting hinge binders that have been underexplored within the tyrosine kinase subfamily. Through this study, the imidazolopyridine ring was selected as a novel c-Met hinge-binding inhibitor scaffold. A series of derivatives was prepared, and the structureactivity relationships were studied. Among these, one compound in particular showed excellent activities in enzymatic and cellular assays, good in vitro metabolic stability, and favorable pharmacokinetic parameters. When administered orally, the compound inhibited tumor growth in an NIH-3T3/TPR-Met xenograft model and did not show adverse effects on body weight. The present work not only conceptually demonstrates a new route for designing novel kinase inhibitors by using known structural information of ligandhinge interactions but also provides a series of imidazolopyridine derivatives as potent c-Met inhibitors. |
| WOS关键词 | RECEPTOR TYROSINE KINASE ; IDENTIFICATION ; METASTASIS ; ACTIVATION ; MECHANISM ; GROWTH ; MODEL |
| 资助项目 | Natural Science Foundation of China[30725046] ; Natural Science Foundation of China for Innovation Research Group[81021062] ; National Natural Science Foundation of China[81072580] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program", China[2009ZX09301-001] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program", China[2009ZX09501-010] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000304438900011 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278062]  |
| 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 药物化学研究室 |
| 通讯作者 | Chen, Danqi |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, Beijing 100864, Peoples R China; 2.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 | Chen, Danqi,Wang, Ying,Ma, Yuchi,et al. Discovery of 3H-Imidazo[4,5-b]pyridines as Potent c-Met Kinase Inhibitors: Design, Synthesis, and Biological Evaluation[J]. CHEMMEDCHEM,2012,7(6):1057-1070. |
| APA | Chen, Danqi.,Wang, Ying.,Ma, Yuchi.,Xiong, Bing.,Ai, Jing.,...&Shen, Jingkang.(2012).Discovery of 3H-Imidazo[4,5-b]pyridines as Potent c-Met Kinase Inhibitors: Design, Synthesis, and Biological Evaluation.CHEMMEDCHEM,7(6),1057-1070. |
| MLA | Chen, Danqi,et al."Discovery of 3H-Imidazo[4,5-b]pyridines as Potent c-Met Kinase Inhibitors: Design, Synthesis, and Biological Evaluation".CHEMMEDCHEM 7.6(2012):1057-1070. |
入库方式： OAI收割
来源：上海药物研究所
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