Identification of a potent and selective non-basic cathepsin K inhibitor.

Journal Article (Journal Article)

Based on our previous study with trifluoroethylamine as a P2-P3 amide isostere of cathepsin K inhibitor, further optimization led to identification of compound 22 (L-873724) as a potent and selective non-basic cathepsin K inhibitor. This compound showed excellent pharmacokinetics and efficacy in an ovariectomized (OVX) rhesus monkey model. The volumes of distribution close to unity were consistent with this compound not being lysosomotropic, which is a characteristic of basic cathepsin K inhibitors.

Full Text

Duke Authors

Cited Authors

  • Li, CS; Deschenes, D; Desmarais, S; Falgueyret, J-P; Gauthier, JY; Kimmel, DB; Léger, S; Massé, F; McGrath, ME; McKay, DJ; Percival, MD; Riendeau, D; Rodan, SB; Thérien, M; Truong, V-L; Wesolowski, G; Zamboni, R; Black, WC

Published Date

  • April 2006

Published In

Volume / Issue

  • 16 / 7

Start / End Page

  • 1985 - 1989

PubMed ID

  • 16413777

Electronic International Standard Serial Number (EISSN)

  • 1464-3405

International Standard Serial Number (ISSN)

  • 0960-894X

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2005.12.071


  • eng