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 P2 elements led to 100-fold enhancements in inhibitory activity. Modifications to one of these leads resulted in an orally bioavailable cathepsin K inhibitor.
Barrett, David G.,Catalano, John G.,Deaton, David N.,Long, Stacey T.,McFadyen, Robert B.,Miller, Aaron B.,Miller, Larry R.,Wells-Knecht, Kevin J.,Wright, Lois L.