Author/Authors :
Chun-Sing Li، نويسنده , , Denis Deschênes، نويسنده , , Sylvie Desmarais، نويسنده , , Jean-Pierre Falgueyret، نويسنده , , Jacques Yves Gauthier، نويسنده , , Donald. B. Kimmel، نويسنده , , Serge Léger، نويسنده , , Frédéric Massé، نويسنده , , Mary E. McGrath and Bradley A. Katz، نويسنده , , Daniel J. McKay، نويسنده , , M. David Percival، نويسنده , , Denis Riendeau، نويسنده , , Sevgi B. Rodan، نويسنده , , Michel Thérien، نويسنده , , Vouy Linh Truong، نويسنده , , Gregg Wesolowski، نويسنده , , Robert Zamboni، نويسنده , , W. Cameron Black، نويسنده ,
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.
Keywords :
cysteine protease , osteoporosis , L-873724 , Non-basic cathepsin K inhibitor , bone resorption , Cathepsin K , Cathepsin K inhibitor
