7-[1H-Indol-2-yl]-2,3-dihydro-isoindol-1-ones as dual Aurora-A/VEGF-R2 kinase inhibitors: design, synthesis, and biological activity

Bioorg Med Chem Lett. 2008 Sep 15;18(18):5130-3. doi: 10.1016/j.bmcl.2008.07.090. Epub 2008 Jul 26.

Abstract

A novel series of 7-[1H-indol-2-yl]-2,3-dihydro-isoindol-1-ones designed to be inhibitors of VEGF-R2 kinase was synthesized and found to potently inhibit VEGF-R2 and Aurora-A kinases. The structure-based design, synthesis, and initial SAR of the series are discussed.

MeSH terms

  • Animals
  • Aurora Kinase A
  • Aurora Kinases
  • Combinatorial Chemistry Techniques
  • Drug Design
  • Indoles* / chemical synthesis
  • Indoles* / pharmacology
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factors / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Indoles
  • Vascular Endothelial Growth Factors
  • Receptor Protein-Tyrosine Kinases
  • Aurka protein, mouse
  • Aurora Kinase A
  • Aurora Kinases
  • Protein Serine-Threonine Kinases