Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Design of Cathepsin K Inhibitors for Osteoporosis

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

Volume 5, Issue 16, 2005

Page: [1639 - 1675] Pages: 37

DOI: 10.2174/156802605775009676

Price: $65

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

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


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy