2. Academic Validation
  3. Identification of a potent and selective non-basic cathepsin K inhibitor

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

  • Bioorg Med Chem Lett. 2006 Apr 1;16(7):1985-9. doi: 10.1016/j.bmcl.2005.12.071.
Chun Sing Li 1,  Denis Deschenes,  Sylvie Desmarais,  Jean-Pierre Falgueyret,  Jacques Yves Gauthier,  Donald B Kimmel,  Serge Léger,  Frédéric Massé,  Mary E McGrath,  Daniel J McKay,  M David Percival,  Denis Riendeau,  Sevgi B Rodan,  Michel Thérien,  Vouy-Linh Truong,  Gregg Wesolowski,  Robert Zamboni,  W Cameron Black
Affiliations

Affiliation

  • 1 Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe-Claire-Dorval, Que., Canada H9R 4P8. chunsing_li@merck.com
PMID: 16413777 DOI: 10.1016/j.bmcl.2005.12.071
Abstract

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.

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