784182-05-4Relevant academic research and scientific papers
Exploration of the P2-P3 SAR of aldehyde cathepsin K inhibitors
Boros, Eric E.,Deaton, David N.,Hassell, Anne M.,McFadyen, Robert B.,Miller, Aaron B.,Miller, Larry R.,Paulick, Margot G.,Shewchuk, Lisa M.,Thompson, James B.,Willard Jr., Derril H.,Wright, Lois L.
, p. 3425 - 3429 (2007/10/03)
The synthesis and biological activity of a series of aldehyde inhibitors of cathepsin K are reported. Exploration of the properties of the S2 and S3 subsites with a series of carbamate derivatized norleucine aldehydes substituted at the P2 and P3 positions afforded analogs with cathepsin K IC50s between 600nM and 130pM.
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.
