Orally bioavailable small molecule ketoamide-based inhibitors of cathepsin K

Bioorg Med Chem Lett. 2004 May 17;14(10):2543-6. doi: 10.1016/j.bmcl.2004.02.085.

Abstract

An orally available series of ketoamide-based inhibitors of cathepsin K has been identified. Starting from a potent inhibitor with poor oral bioavailability, modifications to P1 and P1' elements led to enhancements in solubility and permeability. These improvements resulted in orally available cathepsin K inhibitors.

MeSH terms

  • Administration, Oral
  • Amides / administration & dosage
  • Amides / chemical synthesis*
  • Amides / pharmacology*
  • Animals
  • Biological Availability
  • Cathepsin K
  • Cathepsins / antagonists & inhibitors*
  • Cell Line
  • Dogs
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Inhibitory Concentration 50
  • Pharmacokinetics
  • Structure-Activity Relationship

Substances

  • Amides
  • Cathepsins
  • CTSK protein, human
  • Cathepsin K