Isoindolinone ureas: a novel class of KDR kinase inhibitors

Bioorg Med Chem Lett. 2004 Sep 6;14(17):4505-9. doi: 10.1016/j.bmcl.2004.06.041.


A series of substituted isoindolinone ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 14c, are potent inhibitors of KDR both enzymatically (< 50 nM) and cellularly < or = 100 nM). A 3D KDR/CDK2/MAP kinase overlay model with several structurally related tyrosine kinase inhibitors was used to predict the binding interactions of the isoindolinone ureas with the KDR active site.

MeSH terms

  • Animals
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Mice
  • NIH 3T3 Cells
  • Urea / chemistry*
  • Urea / pharmacology
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • Enzyme Inhibitors
  • Indoles
  • Urea
  • Vascular Endothelial Growth Factor Receptor-2