Chatterjee, Arnab, Liu, Hong, Tully, David, Guo, Jianhua, Epple, Robert, Russo, Ross, Williams, Jennifer, Roberts, Michael, Tuntland, Tove, Chang, Jonathan, Gordon, P., Hollenbeck, Thomas, Tumanut, Christine, Li, Jun and Harris, Jennifer (2007) Synthesis and SAR of succinamide peptidomimetic inhibitors of cathepsin S. Bioorganic & Medicinal Chemistry Letters, 17 (10). pp. 2899-2903. ISSN 0960-894X

Abstract

Peptidic, non-covalent inhibitors of lysosomal cysteine protease cathepsin S (1 and 2) were investigated due to low oral bioavailability, leading to an improved series of peptidomimetic inhibitors. Utilizing phenyl succinamides as the P2 residue increased the oral exposure of this lead series of compounds, while retaining selective inhibition of the cathepsin S isoform. Concurrent investigation of the P1 and P2 subsites resulted in the discovery of several potent and selective inhibitors of cathepsin S with good pharmacokinetic properties due to the elimination of saturated aliphatic P2 residues.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2007.02.049
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	Cathepsin S; Lysosomal proteases; Succinamides
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2007.02.049
Date Deposited:	14 Dec 2009 14:05
Last Modified:	31 Jan 2013 01:27
URI:	https://oak.novartis.com/id/eprint/120