863651-58-5Relevant articles and documents
P2-P3 conformationally constrained ketoamide-based inhibitors of cathepsin K
Barrett, David G.,Boncek, Virginia M.,Catalano, John G.,Deaton, David N.,Hassell, Anne M.,Jurgensen, Cynthia H.,Long, Stacey T.,McFadyen, Robert B.,Miller, Aaron B.,Miller, Larry R.,Payne, J. Alan,Ray, John A.,Samano, Vicente,Shewchuk, Lisa M.,Tavares, Francis X.,Wells-Knecht, Kevin J.,Willard Jr., Derril H.,Wright, Lois L.,Zhou, Hui-Qiang Q.
, p. 3540 - 3546 (2007/10/03)
An orally bioavailable series of ketoamide-based cathepsin K inhibitors with good pharmacokinetic properties has been identified. Starting from a potent inhibitor endowed with poor drug properties, conformational constraint of the P2-P3 linker and modifications to P1′ elements led to an enhancement in potency, solubility, clearance, and bioavailability. These optimized inhibitors attenuated bone resorption in a rat TPTX hypocalcemic bone resorption model.
