N-(Aryl)-4-(azolylethyl)thiazole-5-carboxamides: novel potent inhibitors of VEGF receptors I and II

Bioorg Med Chem Lett. 2006 Feb;16(3):602-6. doi: 10.1016/j.bmcl.2005.10.058. Epub 2005 Nov 3.

Abstract

Novel potent derivatives of N-(aryl)-4-(azolylethyl)thiazole-5-carboxamides are described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Several compounds display VEGFR-2 inhibitory activity reaching IC(50)<100 nM in both enzymatic and cellular assays. The compounds also inhibit the related tyrosine kinase, VEGFR-1. By controlling the substitution pattern on the 5-carboxamido pharmacophore, both dual and specific VEGFR-2 thiazoles were identified.

MeSH terms

  • Amides / chemistry
  • Animals
  • CHO Cells
  • Cricetinae
  • Enzyme Inhibitors / pharmacology*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Thiazoles / chemistry
  • Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*

Substances

  • Amides
  • Enzyme Inhibitors
  • Thiazoles
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2