Compounds and methods for treating inflammatory and fibrotic disorders

Abstract

Disclosed are compounds and methods for treating inflammatory and fibrotic disorders, including methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of the p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the p38 MAPK by the compound. Also disclosed are derivatives and analogs of pirfenidone, useful for modulating a stress activated protein kinase (SAPK) system. Mederski et al., Tetrahedron (1999), 55(44), 12757-12770.* Azuma et al., 'A placebo control and double blind phase II clinical study of pirfenidone in patients with idiopathic pulmonary fibrosis in Japan', Am J Respir Crit Care Med., 165:A729 (2002). Badger, et al., 'Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function', J. Pharmacol. Exp. Ther. 279:1453-61 (1996).