Identification of a Novel Class of Succinyl-Nitrile-Based Cathepsin S Inhibitors

Bioorg Med Chem Lett. 2007 May 1;17(9):2465-9. doi: 10.1016/j.bmcl.2007.02.046. Epub 2007 Feb 23.

Abstract

The synthesis and in vitro activities of a series of succinyl-nitrile-based inhibitors of Cathepsin S are described. Several members of this class show nanomolar inhibition of the target enzyme as well as cellular potency. The inhibitors displaying the greatest potency contain N-alkyl substituted piperidine and pyrrolidine rings spiro-fused to the alpha-carbon of the P1 residue.

MeSH terms

  • Catalytic Domain
  • Cathepsins / antagonists & inhibitors*
  • Chemistry, Pharmaceutical / methods*
  • Dipeptides / chemistry
  • Drug Design
  • Humans
  • Models, Chemical
  • Molecular Conformation
  • Nitriles / chemistry*
  • Nitriles / classification
  • Peptides / chemistry
  • Piperidines / chemistry
  • Pyrrolidines / chemistry
  • Structure-Activity Relationship

Substances

  • Dipeptides
  • Nitriles
  • Peptides
  • Piperidines
  • Pyrrolidines
  • piperidine
  • Cathepsins
  • cathepsin S
  • pyrrolidine