中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 药理学第一研究室
Discovery of potent 1H-imidazo[4,5-b]pyridine-based c-Met kinase inhibitors via mechanism-directed structural optimization

文献类型：期刊论文

作者An, Xiao-De1,2; Liu, Hongyan2; Xu, Zhong-Liang2; Jin, Yi3; Peng, Xia2; Yao, Ying-Ming1; Geng, Meiyu2; Long, Ya-Qiu2
刊名BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
出版日期2015-02-01
卷号25期号:3页码:708-716
关键词c-Met tyrosine kinase Small molecule inhibitor Imidazonaphthyridinone Imidazopyridine Binding mode Pyridone-3-carboxamide Cyclopropane-1,1-dicarboxamide
ISSN号0960-894X
DOI10.1016/j.bmcl.2014.11.070
文献子类Article
英文摘要Starting from our previously identified novel c-Met kinase inhibitors bearing 1H-imidazo[4,5-h][1,6]naphthyridin-2(3H)-one scaffold, a global structural exploration was conducted to furnish an optimal binding motif for further development, directed by the enzyme inhibitory mechanism. First round SAR study picked two imidazonaphthyridinone frameworks with 1,8- and 3,5-disubstitution pattern as class I and class II c-Met kinase inhibitors, respectively. Further structural optimization on type II inhibitors by truncation of the imidazonaphthyridinone core and incorporation of an N-phenyl cyclopropane-1,1-dicarboxamide pharmacophore led to the discovery of novel imidazopyridine-based c-Met kinase inhibitors, displaying nanomolar enzyme inhibitory activity and improved Met kinase selectivity. More significantly, the new chemotype c-Met kinase inhibitors effectively inhibited Met phosphorylation and its downstream signaling as well as the proliferation of Met-dependent EBC-1 human lung cancer cells at submicromolar concentrations. (C) 2014 Elsevier Ltd. All rights reserved.
WOS关键词GROWTH-FACTOR RECEPTOR ; TYROSINE KINASE ; ONCOGENE ADDICTION ; CANCER ; IDENTIFICATION ; DERIVATIVES ; RESISTANCE ; PROGRESS ; DESIGN
资助项目National Science Foundation of China[81325020] ; National Science Foundation of China[21302201] ; National Science Foundation of China[81321092] ; National Science Foundation of China[91229205] ; National Program on Key Basic Research Project of China[2012CB910704] ; National S&T Major Projects of China[2012ZX09301001-007] ; Science and Technology Commission of Shanghai Municipality, China[13ZR1447700]
WOS研究方向Pharmacology & Pharmacy ; Chemistry
语种英语
WOS记录号WOS:000347901700054
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/276661]  
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Yao, Ying-Ming
作者单位1.Soochow Univ, Coll Chem Chem Engn & Mat Sci, Key Lab Organ Synth Jiangsu Prov, Suzhou 215123, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
3.Yunnan Univ, Sch Chem Sci & Technol, Kunming 650091, Peoples R China
推荐引用方式
GB/T 7714		 An, Xiao-De,Liu, Hongyan,Xu, Zhong-Liang,et al. Discovery of potent 1H-imidazo[4,5-b]pyridine-based c-Met kinase inhibitors via mechanism-directed structural optimization[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2015,25(3):708-716.
APA An, Xiao-De.,Liu, Hongyan.,Xu, Zhong-Liang.,Jin, Yi.,Peng, Xia.,...&Long, Ya-Qiu.(2015).Discovery of potent 1H-imidazo[4,5-b]pyridine-based c-Met kinase inhibitors via mechanism-directed structural optimization.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,25(3),708-716.
MLA An, Xiao-De,et al."Discovery of potent 1H-imidazo[4,5-b]pyridine-based c-Met kinase inhibitors via mechanism-directed structural optimization".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 25.3(2015):708-716.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。