Synthesis of 1,4-disubstituted-piperazines as potential antihypertensive agents

A new series of 1,4-disubstituted piperazines was synthesized. The pharmacological screening of some of the synthesized compounds revealed that compound III displayed a potent hypotenisve activity with rapid onset and prolonged duration of action, that was not accompanied by compensatory tachycardia. Moreover, compound III was found to be a competitive alpha-adrenergic blocker as well as a preferential beta 1- blocker. Compounds that block alpha adrenoreceptors do not show a great deal of structural similarity. Thus among the diverse structures which possess potent alpha- adrenergic blocking activity there are the 1,4-disubstituted piperazines Prazocin, which belongs to the latter class is now being used in clinical practice as an antihypertensive agent [12]. Consequently, a new series of 1-arylpiperazine derivatives were synthesized for evaluation as potential adrenergic blockers