Exploration of the P2-P3 SAR of aldehyde cathepsin K inhibitors

Bioorg Med Chem Lett. 2004 Jul 5;14(13):3425-9. doi: 10.1016/j.bmcl.2004.04.084.

Abstract

The synthesis and biological activity of a series of aldehyde inhibitors of cathepsin K are reported. Exploration of the properties of the S2 and S3 subsites with a series of carbamate derivatized norleucine aldehydes substituted at the P2 and P3 positions afforded analogs with cathepsin K IC50s between 600 nM and 130 pM.

MeSH terms

  • Aldehydes / chemistry*
  • Aldehydes / pharmacology
  • Binding Sites / drug effects
  • Carbamates / chemistry
  • Cathepsin K
  • Cathepsins / antagonists & inhibitors*
  • Humans
  • Inhibitory Concentration 50
  • Norleucine / chemistry
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Aldehydes
  • Carbamates
  • Protease Inhibitors
  • Norleucine
  • Cathepsins
  • CTSK protein, human
  • Cathepsin K