Synthesis of New Pyridazinones Substituted by 4-Arylpiperazin-1-yl-carbonylalkyl Moieties and their Analgesic Properties in Mice

A new series of 4,6-diaryl pyridazin-3-ones substituted on the nitrogen atom in the 2-position have been prepared and evaluated for their analgesic activity in the phenylbenzo-quinone-induced abdominal constriction test. Most of the eighteen compounds displayed significant antinociceptive effects with ED50 ranging from 22-2 to 76-7 mg kg−1, intraperitoneally. Pyridazinones 4f and 5f were among the most interesting derivatives with marked analgesic properties associated to weak neurosedative activities (ED50 = 83-3 and 247-2 mg kg−1, i.p., respectively). Further investigations provided support for the hypothesis that the antinociceptive action of 4f and 5f probably resulted from interactions with opioidergic, 5-hydroxytryptaminergic and noradrenergic pathways.