Arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 2: Optimization of P1 and N-aryl

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1486-90. doi: 10.1016/j.bmcl.2005.12.056. Epub 2006 Jan 18.

Abstract

A systematic study of anilines led to the discovery of a metabolically robust fluoroindoline replacement for the alkoxy aniline toxicophore in 1. Investigations of the P1 pocket resulted in the discovery of a wide tolerance of functionality leading to the discovery of 11 as a potent and selective inhibitor of cathepsin S.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Amination
  • Benzene Derivatives / chemical synthesis
  • Benzene Derivatives / chemistry
  • Benzene Derivatives / pharmacology
  • Binding Sites
  • Cathepsin K
  • Cathepsin L
  • Cathepsins / antagonists & inhibitors*
  • Cathepsins / chemistry
  • Cathepsins / metabolism
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / chemistry
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Drug Design*
  • Ethanol / chemistry
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Amides
  • Benzene Derivatives
  • Cysteine Proteinase Inhibitors
  • Ethanol
  • Cathepsins
  • Cysteine Endopeptidases
  • Cathepsin L
  • cathepsin S
  • Cathepsin K