Identification of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors

Bioorg Med Chem Lett. 2008 Jan 1;18(1):386-90. doi: 10.1016/j.bmcl.2007.10.018. Epub 2007 Oct 17.

Abstract

Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have been identified to be orally bioavailable and efficacious in the mouse edema model.

MeSH terms

  • Administration, Oral
  • Aminopyridines / chemical synthesis
  • Aminopyridines / chemistry*
  • Aminopyridines / pharmacokinetics
  • Aminopyridines / pharmacology*
  • Animals
  • Biological Availability
  • Edema / drug therapy
  • Edema / metabolism
  • Female
  • Inhibitory Concentration 50
  • Mice
  • Models, Molecular
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / pharmacology
  • Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Urea / analogs & derivatives*
  • Urea / chemical synthesis
  • Urea / pharmacology
  • Uterine Diseases / drug therapy
  • Uterine Diseases / metabolism

Substances

  • Aminopyridines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Urea
  • Receptors, Platelet-Derived Growth Factor
  • Receptors, Vascular Endothelial Growth Factor