6-Phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile as cathepsin S inhibitors

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4350-4. doi: 10.1016/j.bmcl.2010.06.072. Epub 2010 Jun 17.

Abstract

6-Phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile analogues were identified as potent and selective cathepsin S inhibitor against both purified enzyme and in human JY cell based cellular assays. This core has a very stable thio-trapping nitrile war-head in comparison with the well reported pyrimidine-2-carbonitrile cysteine cathepsin inhibitors. Compound 47 is also very potent in in vivo mouse spleenic Lip10 accumulation assays.

MeSH terms

  • Animals
  • Binding Sites
  • Cathepsins / antagonists & inhibitors*
  • Cathepsins / metabolism
  • Cell Line
  • Crystallography, X-Ray
  • Humans
  • Mice
  • Nitriles / chemical synthesis
  • Nitriles / chemistry*
  • Nitriles / pharmacokinetics
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacokinetics
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / pharmacokinetics
  • Structure-Activity Relationship

Substances

  • 6-phenyl-1H-imidazo(4,5-c)pyridine-4-carbonitrile
  • Nitriles
  • Protease Inhibitors
  • Pyridines
  • Cathepsins
  • cathepsin S