A new nonsteroidal analgesic-antiinflammatory agent. Synthesis and activity of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone and related compounds

Abstract

In order to examine analgesic and antinflammatory activities, various 2-alkyl- or 2-alkenyl-4-alkoxy-5-(substituted amino)-3(2H)-pyridazinones were prepared. Among the compounds prepared, 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (8) was evaluated to be the most attractive compound as an analgesic-antiinflammatory agent. Compound 8 was shown to be more potent in analgesic and antiinflammatory activities and less potent in toxicity than aminopyrine and phenylbutazone. Some pyridazinone derivatives in which possible active sites of 8 are eliminated and altered were prepared, and their activities were evaluated by means of analogous assays. On the basis of available data, the structure-activity relationship in a series of 4-alkoxy-2-substituted-5-(substituted amino)-3(2H)-pyridazinones was also discussed.