期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 120, 期 -, 页码 37-50出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2016.04.062
关键词
Synthesis; Bipyridine derivatives; Aza-aryl formamides; c-Met; Cytotoxicity
资金
- Program for Liaoning Excellent Talents in University [LR2014030, 2013921042]
- National Natural Science Foundation of China [21002065]
Six series of novel 4-(2-fluorophenoxy)-3,3'-bipyridine derivatives conjugated with aza-aryl formamide/amine scaffords were designed and synthesized through a structure-based molecular hybridization approach. The target compounds were evaluated for c-Met kinase inhibitory activities and cytotoxicity against four cancer cell lines (HT-29, A549, MKN-45 and MDA-MB-231) in vitro. Most compounds exhibited moderate to excellent potency, and the most promising candidate 26c (c-Met kinase IC50 = 8.2 nM) showed a 4.7-fold increase in cytotoxicity against c-Met-addicted MKN-45 cell line in vitro (IC50 = 3 nM), superior to that of Foretinib (IC50 = 23 nM). The preliminary structure-activity relationship indicated that a 1H-benzo [e] [1,3,4]thiadiazine-3-carboxamide-4,4-dioxide moiety as linker contributed to the antitumor potency. (C) 2016 Elsevier Masson SAS. All rights reserved.
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