Design of Cathepsin K Inhibitors for Osteoporosis

Title: Design of Cathepsin K Inhibitors for Osteoporosis

Volume: 5 Issue: 16

Author(s): David N. Deaton and Francis X. Tavares

Affiliation:

Keywords: Bisphosphonates, osteoprotegerin, anti-resorptive therapy, bone mineral density (BMD), elastolytic activity, semicarbazones, ketoheterocycles

Abstract: Osteoporosis is a progressive, debilitating bone disease resulting in increased cost and morbidity to the elderly. This review summarizes the therapeutic approaches taken in the treatment of osteoporosis with particular emphasis on cathepsin K inhibitors. Cathepsin K, a cysteine protease predominantly expressed in osteoclasts, is a key player involved in bone matrix degradation. Both genetic ablation and small molecule inhibitor strategies versus cathepsin K have validated the importance of this enzyme in bone resorption. Starting from aldehyde-based leads, this review synopsizes the design of improved small molecule inhibitors by GlaxoWellcome researchers. These efforts involved the evaluation of various warheads, including cyanamides, ketoheterocycles, and ketoamides. Initial structure/activity relationships of aldehyde-based inhibitors proved useful in the design of ketoamide-based cathepsin K inhibitors. Further exploration of

Cite this article as:

Deaton N. David and Tavares X. Francis, Design of Cathepsin K Inhibitors for Osteoporosis, Current Topics in Medicinal Chemistry 2005; 5 (16) . https://dx.doi.org/10.2174/156802605775009676