Design of small molecule ketoamide-based inhibitors of cathepsin K.

Abstract

A novel series of ketoamide-based inhibitors of cathepsin K has been identified. Modifications to P(2) and P(3) elements were crucial to enhancing inhibitory activity. Although not optimized, a selected inhibitor was effective in attenuating type I collagen hydrolysis in a surrogate assay of bone resorption.

• Authors: John G Catalano, David N Deaton, Stacey T Long, Robert B McFadyen, Larry R Miller, J Alan Payne, Kevin J Wells-Knecht, Lois L Wright
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 14 Issue 3 Pg. 719-22 (Feb 09 2004) ISSN: 0960-894X [Print] England
• PMID: 14741275 (Publication Type: Journal Article)

Chemical References

• Collagen Type I
• Cysteine Proteinase Inhibitors
• Cathepsins
• CTSK protein, human
• Cathepsin K

Topics

• Bone Resorption (metabolism)
• Bone and Bones (drug effects, pathology)
• Cathepsin K
• Cathepsins (antagonists & inhibitors)
• Collagen Type I (metabolism)
• Cysteine Proteinase Inhibitors (chemical synthesis, pharmacology)
• Drug Design
• Humans
• Hydrolysis
• Structure-Activity Relationship