Design and synthesis of tetracyclic nonpeptidic biaryl nitrile inhibitors of cathepsin K

Bioorg Med Chem Lett. 2006 Aug 15;16(16):4296-9. doi: 10.1016/j.bmcl.2006.05.061. Epub 2006 Jun 5.

Abstract

The synthesis and biological profile of a novel series of potent and selective inhibitors of cysteine protease cathepsin K (Cat K) are described. Pharmacokinetic evaluation of 12 indicated that some members of this series could be suitable candidates to develop new orally active therapeutic agents for the treatment of osteoporosis.

MeSH terms

  • Area Under Curve
  • Cathepsin B / chemistry
  • Cathepsin K
  • Cathepsin L
  • Cathepsins / antagonists & inhibitors*
  • Cathepsins / chemistry
  • Chemistry, Pharmaceutical
  • Cysteine Endopeptidases / chemistry
  • Drug Design
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Models, Molecular
  • Nitriles / chemistry*
  • Osteoporosis / drug therapy*

Substances

  • Enzyme Inhibitors
  • Nitriles
  • Cathepsins
  • Cysteine Endopeptidases
  • Cathepsin B
  • CTSL protein, human
  • Cathepsin L
  • cathepsin S
  • CTSK protein, human
  • Cathepsin K