Novel Purine Nitrile Derived Inhibitors of the Cysteine Protease Cathepsin K

J Med Chem. 2004 Nov 18;47(24):5833-6. doi: 10.1021/jm0493111.

Abstract

Starting from the high-throughput screening hit 1a, novel cathepsin K inhibitors have been developed based on a purine scaffold. High-resolution X-ray structures of several derivatives have revealed the binding mode of these unique cysteine protease inhibitors.

MeSH terms

  • Animals
  • Binding Sites
  • Cathepsin K
  • Cathepsins / antagonists & inhibitors*
  • Cathepsins / chemistry*
  • Crystallography, X-Ray
  • Cysteine Proteinase Inhibitors / chemical synthesis*
  • Cysteine Proteinase Inhibitors / chemistry
  • Models, Molecular
  • Nitriles / chemical synthesis*
  • Nitriles / chemistry
  • Purines / chemical synthesis*
  • Purines / chemistry
  • Rats
  • Structure-Activity Relationship

Substances

  • Cysteine Proteinase Inhibitors
  • Nitriles
  • Purines
  • Cathepsins
  • Cathepsin K
  • Ctsk protein, rat