Discovery and Optimization of 1-(4-chloro-3-(trifluoromethyl)- phenyl)-3-(2-(amino)pyridin-3-yl)ureas as Novel KDR Kinase Inhibitors

Author(s): Yu Jiao, Fei Huang, Pengfei Xu, Yanmin Zhang, Shangyan Yang, Danfeng Zhang, Tao Lu, Weifang Tang

Journal Name: Medicinal Chemistry

Volume 12 , Issue 4 , 2016

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Abstract:

Kinase insert Domain-containing Receptor (KDR) is one of the currently validated targets for anticancer drug discovery and development. Herein, a series of o-amino-arylurea derivatives have been synthesized and evaluated for their kinase inhibitory activity. The optimization on the basis of biological screening and molecular modeling resulted in obvious increase in KDR kinase inhibitory activity compared with the hit compound. Eventually, we identified a potent inhibitor 5a of 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2-((quinolin-4-ylmethyl) amino)pyridin-3-yl)urea scaffold against KDR (IC50 = 0.0689 µM), which can serve as good starting point for further KDR inhibitor optimization and development.

Keywords: Biological screening, drug design, inhibitor, KDR kinase, optimization, synthesis.

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Article Details

VOLUME: 12
ISSUE: 4
Year: 2016
Page: [328 - 337]
Pages: 10
DOI: 10.2174/1573406412666151215105149
Price: $65

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