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

[ Vol. 12 , Issue. 4 ]


Yu Jiao, Fei Huang, Pengfei Xu, Yanmin Zhang, Shangyan Yang, Danfeng Zhang, Tao Lu and Weifang Tang   Pages 328 - 337 ( 10 )


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.


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


Department of Organic Chemistry, School of Science, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P.R. China.

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