Tully, David, Liu, Hong, Chatterjee, Arnab, Alper, Phillip, Epple, Robert, Williams, Jennifer, Roberts, Michael, Woodmansee, David, Masick, Brian, Tumanut, Christine, Li, Jun, Spraggon, Glen, Hornsby, Michael, Chang, Jonathan, Tuntland, Tove, Hollenbeck, Thomas, Gordon, P., Harris, Jennifer and Karanewsky, Donald (2006) Synthesis and SAR of arylaminoethyl amides as noncovalent inhibitors of cathepsin S: P3 cyclic ethers. Bioorganic & Medicinal Chemistry Letters, 16 (19). pp. 5112-5117. ISSN 0960-894X

Abstract

The synthesis and structure-activity relationship of a series of arylaminoethyl amide cathepsin S inhibitors are reported. Optimization of P3 and P2 groups to improve overall physicochemical properties resulted in significant improvements in oral bioavailability over early lead compounds. An X-ray structure of compound 37 bound to the active site of cathepsin S is also reported.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2006.07.033
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	Cathepsin S; Cysteine protease inhibitor; Noncovalent inhibitor; Peptidomimetic; X-ray structure
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2006.07.033
Date Deposited:	14 Dec 2009 14:04
Last Modified:	31 Jan 2013 01:26
URI:	https://oak.novartis.com/id/eprint/143