Bioorganic & medicinal chemistry letters, 2006-04, Vol.16 (7), p.1985-1989
2006
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Identification of a potent and selective non-basic cathepsin K inhibitor
- Ist Teil von
- Bioorganic & medicinal chemistry letters, 2006-04, Vol.16 (7), p.1985-1989
- Ort / Verlag
- Oxford: Elsevier Ltd
- Erscheinungsjahr
- 2006
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0960-894XeISSN: 1464-3405DOI: 10.1016/j.bmcl.2005.12.071Titel-ID: cdi_proquest_miscellaneous_67689893
- Format
- –
- Schlagworte
- Animals, Biological and medical sciences, Bone resorption, Bones, joints and connective tissue. Antiinflammatory agents, Cathepsin K, Cathepsin K inhibitor, Cathepsins - antagonists & inhibitors, Crystallography, X-Ray, Cysteine protease, Cysteine Proteinase Inhibitors - chemistry, Cysteine Proteinase Inhibitors - pharmacokinetics, Cysteine Proteinase Inhibitors - pharmacology, Female, L-873724, Macaca mulatta, Medical sciences, Models, Molecular, Non-basic cathepsin K inhibitor, Osteoporosis, Ovariectomy, Pharmacology. Drug treatments