STUDIES ON PYRIDAZINONE DERIVATIVES .16. ANALGESIC-ANTIINFLAMMATORY ACTIVITIES OF 3(2H)-PYRIDAZINONE DERIVATIVES

In order to examine analgesic and antiinflammatory activities of the p osition isomers of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone ( 1, emorfazone), an analgesic-antiinflammatory drug, 5-ethoxy-2-methyl- 4-morpholino-3(2H)-pyridazinone (2), 6-ethoxy-2-methyl-4-morpholino-3( 2H)-pyr dazinone (3) and 6-ethoxy-2-methyl-5-morpholino-3 (2H)-pyridaz inone (4) were prepared. Since 4 showed the most strong activity among the compounds tested, various 6-alkoxy- or 6-allyloxy-2-alkyl- or 2-c yclohexyl- or 2-phenyl-5-substituted amino-3(2H)-pyridazinones (15, 16 ) were prepared and examined for their activities. As a result, 4 and 2-methyl-5-morpholino-6-n-propoxy- or 6-n-butoxy-3 (2H)-pyridazinone ( 15b,c) and 6-ethoxy-2-ethyl-5 -morpholino-3(2H)-pyridazinone (151) wer e revealed to be more potent in analgesic and antipyretic activities t han commercial drugs (1, aminopyrine, mepirizole, tiaramide HCl, pheny lbutazone, mefenamic acid): On the basis of the available data, the st ructure-activity relationship in a series of 6-alkoxy-2-alkyl-5-substi tuted amino-3(2H)-pyridazinones (15, 16) was also discussed.