期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 123, 期 -, 页码 431-446出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2016.07.059
关键词
Synthesis; 4-Phenoxyquinoline derivatives; c-Met inhibitors; Antitumor activity
资金
- National Natural Science Foundation of China [81573295]
- National Science Fund for fostering talents in basic science [J1103606]
A series of novel 4-phenoxyquinoline derivatives containing 1,2,4-triazolone moiety were synthesized and evaluated for their in vitro cytotoxic activity against four cancer cell lines (HT-29, H460, A549 and MKN-45). Most of the compounds exhibited moderate-to-significant cytotoxicity. Compounds 33, 37, 39, 44, 46, 47, 53, 55, 61, 64 and 66 were further examined for their inhibitory activity against c-Met kinase. The most promising compound 47 (with c-Met IC50 value of 1.57 nM) showed remarkable cytotoxicity against HT-29, H460, A549 and MKN-45 cell lines with IC50 values of 0.08 mu M, 0.14 mu M, 0.11 mu M and 0.031 mu M, respectively, and thus it was 1.1- to 23- fold more potent than foretinib. Their preliminary structure-activity relationships (SARs) studies indicate that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity. (C) 2016 Published by Elsevier Masson SAS.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据