期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 22, 期 4, 页码 1236-1249出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2014.01.014
关键词
c-Met; Receptor tyrosine kinase; Anti-tumor; Quinoline derivatives; Pyrimidine-2,4,6-trione
资金
- National Natural Science Foundation of China (NSFC) [81102470]
- Liaoning Science and Technology Program [2011412004-3]
A series of novel quinoline derivatives bearing 5-(aminomethylene)pyrimidine-2,4,6-trione moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 5 cancer cell lines (HT-29, H460, MKN-45, A549, and U87MG) in vitro. Most compounds showed moderate to excellent potency, with the most promising analogue 45 (c-Met half-maximal inhibitory concentration [IC50] = 1.15 nM) showing high selectivity versus 5 other tyrosine kinases, VEGFR-2, Flt-3, PDGFR-beta, c-Kit, and EGFR. Structure-activity relationship studies indicated that electron-donating groups on the phenyl ring at the 3-position of pyrimidine-2,4,6-trione were required to increase the electron density on the 5-(aminomethylene) pyrimidine-2,4,6-trione moiety. (C) 2014 Elsevier Ltd. All rights reserved.
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