Arylamine based cathepsin K inhibitors: investigating P3 heterocyclic substituents

Bioorg Med Chem. 2006 Oct 15;14(20):6807-19. doi: 10.1016/j.bmc.2006.06.031. Epub 2006 Jul 7.

Abstract

A modification of novel cathepsin K inhibitors I was carried out. The structural design was aimed at reducing the lipophilic character of compounds I for obtaining better pharmacokinetic profiles. This modification afforded several less lipophilic compounds with good inhibitory activities and pharmacokinetic profiles, although the enzyme selectivity over cathepsin S was left at issue.

MeSH terms

  • Amines / chemical synthesis
  • Amines / chemistry
  • Amines / pharmacology*
  • Cathepsin B / antagonists & inhibitors
  • Cathepsin K
  • Cathepsin L
  • Cathepsins / antagonists & inhibitors*
  • Cysteine Endopeptidases
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology*
  • Humans
  • Molecular Conformation
  • Recombinant Proteins / antagonists & inhibitors
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amines
  • Enzyme Inhibitors
  • Heterocyclic Compounds
  • Recombinant Proteins
  • Cathepsins
  • Cysteine Endopeptidases
  • Cathepsin B
  • CTSL protein, human
  • Cathepsin L
  • cathepsin S
  • CTSK protein, human
  • Cathepsin K