A structural screening approach to ketoamide-based inhibitors of cathepsin K

Several novel ketoamide-based inhibitors of cathepsin K have been identified. Starting from a modestly potent inhibitor, structural screening of P-2 elements led to 100-fold enhancements in inhibitory activity. Modifications to one of these leads resulted in an orally bioavailable cathepsin K inhibitor. (c) 2005 Elsevier Ltd. All rights reserved.