Irie, Osamu, Ehara, Takeru, Iwasaki, Atsuko, Yokokawa, Fumiaki, Sakaki, Junichi, Hirao, Hajime, Kanazawa, Takanori, Teno, Naoki, Horiuchi, Miyuki, Umemura, Ichiro, Gunji, Hiroki, Masuya, Keiichi, Hitomi, Yuko, Iwasaki, Genji, Nonomura, Kazuhiko, Tanabe, Keiko, Fukaya, Hiroaki, Kosaka, Takatoshi, Snell, Chris and Hallett, Allan (2008) Discovery of selective and nonpeptidic cathepsin S inhibitors. Bioorganic & Medicinal Chemistry Letters, 18 (14). pp. 3959-3962. ISSN 1464-3405

Abstract

Nonpeptidic, selective, and potent cathepsin S inhibitors were derived from an in-house pyrrolopyrimidine cathepsin K inhibitor by modification of the P2 and P3 moieties. The pyrrolopyrimidine-based inhibitors show nanomolar inhibition of cathepsin S with over 100-fold selectivity against other cysteine proteases, including cathepsin K and L. Some of the inhibitors showed cellular activities in mouse splenocytes as well as oral bioavailabilities in rats.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2008.06.009
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	Cathepsin S inhibitor; Pyrrolopyrimidine; Nitrile; Nonpeptidic; Cysteine protease
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2008.06.009
Date Deposited:	14 Dec 2009 13:53
Last Modified:	31 Jan 2013 01:06
URI:	https://oak.novartis.com/id/eprint/803