4-(Azolylphenyl)-phthalazin-1-amines: Novel inhibitors of VEGF receptors I and II

Chem Biol Drug Des. 2006 Dec;68(6):308-13. doi: 10.1111/j.1747-0285.2006.00456.x.

Abstract

Novel potent derivatives of phthalazine are described as ATP-competitive inhibitors of vascular endothelial growth factor receptors I and II (VEGFR-1/2). A number of compounds display VEGFR-2 inhibitory activity reaching that of Vatalanib 3 (IC50 < 100 nm) in an HTRF enzymatic assay. Several derivatives also show good potential for the development as VEGFR-2 specific inhibitors showing 15-20-fold selectivity over VEGFR-1.

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Binding, Competitive
  • Drug Design
  • Humans
  • Phthalazines / chemistry*
  • Phthalazines / pharmacology*
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Pyridines / pharmacology
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*

Substances

  • Phthalazines
  • Protein Kinase Inhibitors
  • Pyridines
  • vatalanib
  • Adenosine Triphosphate
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2