Exploration of cathepsin S inhibitors characterized by a triazole P1-P2 amide replacement

Bioorg Med Chem Lett. 2012 Dec 1;22(23):7189-93. doi: 10.1016/j.bmcl.2012.09.054. Epub 2012 Oct 2.

Abstract

This paper details exploration of a class of triazole-based cathepsin S inhibitors originally reported by Ellman and co-workers. SAR studies involving modifications across the whole inhibitor provide a perspective on the strengths and weaknesses of this class of inhibitors. In addition, we put the unique characteristics of this class of compounds into perspective with other classes of cathepsin S inhibitors.

MeSH terms

  • Amides / chemistry*
  • Cathepsins / antagonists & inhibitors*
  • Cathepsins / metabolism
  • Half-Life
  • Humans
  • Microsomes, Liver / metabolism
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacokinetics
  • Protein Binding
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry*
  • Thiophenes / pharmacokinetics
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacokinetics

Substances

  • Amides
  • Protease Inhibitors
  • Thiophenes
  • Triazoles
  • Cathepsins
  • cathepsin S