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ID: ALA1146103

Journal: Bioorg Med Chem Lett

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

Authors: Li CS, Deschenes D, Desmarais S, Falgueyret JP, Gauthier JY, Kimmel DB, Léger S, Massé F, McGrath ME, McKay DJ, Percival MD, Riendeau D, Rodan SB, Thérien M, Truong VL, Wesolowski G, Zamboni R, Black WC.

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.

CiteXplore: 16413777

DOI: 10.1016/j.bmcl.2005.12.071