Revesz, Laszlo, Blum, Ernst, Di Padova, Franco E., Buhl, Thomas, Feifel, Roland, Gram, Hermann, Hiestand, Peter, Manning, Ute and Rucklin, Gerard (2004) Novel p38 inhibitors with potent oral efficacy in several models of rheumatoid arthritis. Bioorganic & Medicinal Chemistry Letters, 14 (13). pp. 3595-3599. ISSN 0960-894X

Abstract

A library of trisubstituted oxazoles, thiazoles, imidazoles (1,2,4- and 2,4,5-substituted) and imidazo[1,2-b]pyridines was prepared and evaluated in vitro as p38alpha inhibitors and in vivo in several models of rheumatoid arthritis. Four structures--32, 37, 45 and 59--were identified as potent inhibitors of p38alpha with high efficacy in the LPS induced TNFalpha release model in the mouse, the adjuvant induced arthritis and the collagen induced arthritis in the rat with ED50s between 1.0 and 9.5 mg/kg p.o.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2004.03.106
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2004.03.106
Date Deposited:	14 Dec 2009 13:55
Last Modified:	31 Jan 2013 01:07
URI:	https://oak.novartis.com/id/eprint/751