l-873724 and relacatib

Odanacatib is a potent, selective, and neutral cathepsin K inhibitor which was developed to address the metabolic liabilities of the Cat K inhibitor L-873724. Substituting P1 and modifying the P2 side chain led to a metabolically robust inhibitor with a long half-life in preclinical species. Odanacatib was more selective in whole cell assays than the published Cat K inhibitors balicatib and relacatib. Evaluation in dermal fibroblast culture showed minimal intracellular collagen accumulation relative to less selective Cat K inhibitors.

Topics: Animals; Azepines; Biphenyl Compounds; Cathepsin K; Cathepsins; Collagen; Cysteine Proteinase Inhibitors; Dogs; Fibroblasts; Humans; Models, Biological; Molecular Structure; Osteoporosis, Postmenopausal; Skin; Structure-Activity Relationship; Sulfones