Potent 2-[(pyrimidin-4-yl)amine}-1,3-thiazole-5-carbonitrile-based inhibitors of VEGFR-2 (KDR) kinase

Bioorg Med Chem Lett. 2006 Mar 1;16(5):1146-50. doi: 10.1016/j.bmcl.2005.11.089. Epub 2005 Dec 20.

Abstract

Pyrimidino-thiazolyl carbonitriles were prepared that are potent VEGFR-2 (KDR) kinase inhibitors. The modification of lead structures resulted in 3m which exhibited the best overall profile in KDR inhibitory activity, iv/po pharmacokinetics, and reduced hERG affinity.

MeSH terms

  • Animals
  • Dogs
  • Macaca mulatta
  • Molecular Structure
  • Nitriles / chemical synthesis*
  • Nitriles / chemistry
  • Nitriles / pharmacology*
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Rats
  • Sensitivity and Specificity
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Thiazoles
  • Vascular Endothelial Growth Factor Receptor-2