Identification of a potent and selective non-basic cathepsin K inhibitor
| Autor: | Serge Leger, Denis Deschenes, Chun Sing Li, Donald B. Kimmel, M. David Percival, Michel Therien, Mary E. McGrath, Robert Zamboni, Daniel J. McKay, Sevgi B. Rodan, Gregg Wesolowski, Denis Riendeau, W. Cameron Black, Jean-Pierre Falgueyret, Sylvie Desmarais, Frédéric Massé, Jacques Yves Gauthier, Vouy-Linh Truong |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Stereochemistry Isostere Ovariectomy Cathepsin K Clinical Biochemistry Pharmaceutical Science Cysteine Proteinase Inhibitors Crystallography X-Ray Biochemistry Chemical synthesis chemistry.chemical_compound Amide Drug Discovery Animals Molecular Biology chemistry.chemical_classification biology Organic Chemistry Biological activity Cathepsins Macaca mulatta Cysteine protease Enzyme chemistry Enzyme inhibitor biology.protein Molecular Medicine Female |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 16:1985-1989 |
| ISSN: | 0960-894X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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