Optimization of triarylimidazoles for Tie2: influence of conformation on potency

Bioorg Med Chem Lett. 2007 Oct 15;17(20):5514-7. doi: 10.1016/j.bmcl.2007.08.052. Epub 2007 Aug 28.

Abstract

In an effort to understand the effect of N-alkylation of triarylimidazoles on Tie2 inhibition, ortho-substituted C-2 aryl analogs were synthesized to investigate the effect of different torsion angles on potency. This exercise resulted in the identification of a potent and selective tetrasubstituted imidazole that was efficacious in an animal model of angiogenesis.

MeSH terms

  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Inhibitory Concentration 50
  • Methylation
  • Models, Molecular
  • Molecular Conformation
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Receptor, TIE-2 / antagonists & inhibitors*
  • Receptor, TIE-2 / chemistry
  • Receptor, TIE-2 / metabolism
  • Sensitivity and Specificity
  • Structure-Activity Relationship

Substances

  • Imidazoles
  • Protein Kinase Inhibitors
  • imidazole
  • Receptor, TIE-2