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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