Download MendeleyIdentification of a potent and selective non-basic cathepsin K inhibitor.
Li, C.S., Deschenes, D., Desmarais, S., Falgueyret, J.P., Gauthier, J.Y., Kimmel, D.B., McGrath, M.E., McKay, D.J., Percival, M.D., Riendeau, D., Rodan, S.B., Truong, V.L., Wesolowski, G., Zamboni, R., Black, W.C.(2006) Bioorg Med Chem Lett 16: 1985-1989
- PubMed: 16413777
- DOI: https://doi.org/10.1016/j.bmcl.2005.12.071
- Primary Citation of Related Structures:
1VSN - PubMed 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.
Organizational Affiliation:
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe-Claire-Dorval, Que., Canada H9R 4P8. chunsing_li@merck.com
