National Center for
1VSN: Crystal Structure Of A Potent Small Molecule Inhibitor Bound To Cathepsin K
Bioorg. Med. Chem. Lett. (2006) 16 p.1985-1989
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.