Synthesis and anti-inflammatory structure-activity relationships of thiazine-quinoline-quinones: Inhibitors of the neutrophil respiratory burst in a model of acute gouty arthritis

Sixteen new thiazine-quinoline-quinones have been synthesised, plus one bicyclic analogue. These compounds inhibited neutrophil superoxide production in vitro with IC(50)s as low 60 nM. Compounds with high in vitro anti-inflammatory activity were also tested in a mouse model of acute inflammation. The most active compounds inhibited both neutrophil infiltration and superoxide production at doses 2.5 mu mol/kg, highlighting their potential for development as novel NSAIDs. (C) 2008 Elsevier Ltd. All rights reserved.