期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 26, 期 7, 页码 1794-1798出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2016.02.037
关键词
Synthesis; Quinoline derivatives; 2-Oxo-4-chloro-1,2-dihydroquinoline; c-Met; Antiproliferative activity
资金
- National Natural Science Foundation of China (NSFC) [81573295]
A series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 2-oxo-4-chloro-1,2-dihydroquinoline- 3-carboxamide moiety were synthesized, and evaluated for their antiproliferative activity against 5 cancer cell lines (H460, HT-29, MKN-45, A549, and U87MG). Most compounds showed moderate to excellent potency, and compared to foretinib, the most promising analog 42 (c-Met/Flt-3 IC50 = 1.21/2.15 nM) showed a 6.1-fold increase in activity against H460 cell line in vitro. The enzymatic assays (c-Met, VEGFR-2, Flt-3, PDGFR-beta, c-Kit, and EGFR) of compound 42 were evaluated in vitro. Docking analysis showed that compound 42 could form three hydrogen bonds with c-Met. Structure-activity relationship studies indicated that a more water-soluble cyclic tertiary amine and electron-withdrawing groups at 4-position of the phenyl ring contribute to the antitumour activity. (C) 2016 Elsevier Ltd. All rights reserved.
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