Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase

Bioorg Med Chem Lett. 2009 Jan 15;19(2):424-7. doi: 10.1016/j.bmcl.2008.11.056. Epub 2008 Nov 20.

Abstract

Selective small molecule inhibitors of Tie-2 kinase are important tools for the validation of Tie-2 signaling in pathological angiogenesis. Reported herein is the optimization of a nonselective scaffold into a potent and highly selective inhibitor of Tie-2 kinase.

MeSH terms

  • Administration, Oral
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Biological Availability
  • Crystallography, X-Ray
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Receptor, TIE-2 / antagonists & inhibitors*

Substances

  • Benzimidazoles
  • Protein Kinase Inhibitors
  • Receptor, TIE-2