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

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

Volume: 12 Issue: 4

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

Affiliation:

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

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.

Cite this article as:

Jiao Yu, Huang Fei, Xu Pengfei, Zhang Yanmin, Yang Shangyan, Zhang Danfeng, Lu Tao and Tang Weifang, Discovery and Optimization of 1-(4-chloro-3-(trifluoromethyl)- phenyl)-3-(2-(amino)pyridin-3-yl)ureas as Novel KDR Kinase Inhibitors, Medicinal Chemistry 2016; 12 (4) . https://dx.doi.org/10.2174/1573406412666151215105149