Discovery of aminopyridines substituted with benzoxazole as orally active c-Met kinase inhibitors

Bioorg Med Chem Lett. 2010 Jul 15;20(14):4223-7. doi: 10.1016/j.bmcl.2010.05.031. Epub 2010 May 15.

Abstract

We report the synthesis and biological evaluation of aminopyridines substituted with benzoxazole. The SAR of the aminopyridines was explored to improve the inhibitory activity against c-Met and to decrease hERG affinity. These studies led to the discovery of amide 24 which showed good c-Met inhibitory potency, low affinity to hERG and favorable pharmacokinetic properties in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aminopyridines / administration & dosage
  • Aminopyridines / chemistry
  • Aminopyridines / pharmacokinetics
  • Aminopyridines / pharmacology*
  • Animals
  • Benzoxazoles / chemistry*
  • Drug Discovery
  • Models, Molecular
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Rats
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Aminopyridines
  • Benzoxazoles
  • Protein Kinase Inhibitors
  • RON protein
  • Receptor Protein-Tyrosine Kinases