Discovery and evaluation of 3-(5-thien-3-ylpyridin-3-yl)-1H-indoles as a novel class of KDR kinase inhibitors

Bioorg Med Chem Lett. 2003 Sep 15;13(18):2973-6. doi: 10.1016/s0960-894x(03)00627-9.


We have discovered 3-(5-thien-3-ylpyridin-3-yl)-1H-indoles as potent inhibitors of KDR kinase activity. This communication details the evolution of this novel class from a potent screening lead of vastly different structure with an emphasis on structural modifications that retained activity and provided improvements in key physical properties. The synthesis and in-depth evaluation of these inhibitors are described.

MeSH terms

  • Administration, Oral
  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / pharmacokinetics
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Biological Availability
  • Cell Line
  • Half-Life
  • Indoles / chemical synthesis*
  • Indoles / pharmacokinetics*
  • Indoles / pharmacology
  • Inhibitory Concentration 50
  • Rats
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*


  • Angiogenesis Inhibitors
  • Indoles
  • Vascular Endothelial Growth Factor Receptor-2