784182-11-2Relevant articles and documents
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.
