4-amino-5-vinyl-3(2H)-pyridazinones and analogues as potent antinociceptive agents: synthesis, SARs, and preliminary studies on the mechanism of action

A series of 4-amino-5-vinyl-3(2H)-pyridazinones and analogues were synthesized and their antinociceptive effect was evaluated in the mouse abdominal constriction model. Several of the novel compounds showed ED50 values in the range 6– 20 mg/kg/sc and demonstrated to be able to completely protect all the treated animals from the effect of the noxious stimulus at 30 mg/kg/sc. SAR studies confirmed the essential role played by an amino or substituted amino function at position 4 and by a vinyl group at position 5 of the diazine system.