568591-16-2Relevant academic research and scientific papers
Potent and selective P2-P3 ketoamide inhibitors of cathepsin K with good pharmacokinetic properties via favorable P 1′, P1, and/or P3 substitutions
Barrett, David G.,Catalano, John G.,Deaton, David N.,Hassell, Anne M.,Long, Stacey T.,Miller, Aaron B.,Miller, Larry R.,Shewchuk, Lisa M.,Wells-Knecht, Kevin J.,Willard Jr., Derril H.,Wright, Lois L.
, p. 4897 - 4902 (2007/10/03)
A series of ketoamides were synthesized and evaluated for inhibitory activity against cathepsin K. Exploration of the interactions between achiral P2 substituents and the cysteine protease based on molecular modeling suggestions resulted in potent cathepsin K inhibitors that demonstrated high selectivity versus cathepsins B, H, and L. Subsequent modifications of the P3, P1, and P1′ moieties afforded orally bioavailable inhibitors. A series of ketoamides were synthesized and evaluated for inhibitory activity against cathepsin K. Exploration of the interactions between achiral P2 substituents and the cysteine protease based on molecular modelling suggestions resulted in potent cathepsin K inhibitors that demonstrated high selectivity versus cathepsins B, H, and L. Subsequent modifications of the P3, P1, and P1′ moieties afforded orally bioavailable inhibitors.
Orally bioavailable small molecule ketoamide-based inhibitors of cathepsin K
Barrett, David G.,Catalano, John G.,Deaton, David N.,Long, Stacey T.,Miller, Larry R.,Tavares, Francis X.,Wells-Knecht, Kevin J.,Wright, Lois L.,Zhou, Hui-Qiang Q.
, p. 2543 - 2546 (2007/10/03)
An orally available series of ketoamide-based inhibitors of cathepsin K has been identified. Starting from a potent inhibitor with poor oral bioavailability, modifications to P1 and P 1′ elements led to enhancements in solubility and permeability. These improvements resulted in orally available cathepsin K inhibitors.
