For much of the past century, drug discovery relied largely on the use of animal models of disease as the first-line screens for testing the compounds produced by medicinal chemists. When compounds were inactive, it was unclear whether this was because they no longer interacted with a molecular target or simply whether they had failed to reach the site of action. Inexorably, the drug discovery paradigm shifted toward a reductionist “one-target, one-disease” approach that continues to dominate the pharmaceutical industry today. There is an increasing readiness to challenge the current paradigm and to consider developing agents that modulate multiple targets simultaneously (polypharmacology), with the aim of enhancing efficacy or improving safety relative to drugs that address only a single target.

                In search of our study a series of hybrid structures of pyrrolidin-2-one and arylalkylpiperazine was design. It was assumed arylalkylpiperazine fragment of molecule determine affinity of molecules obtained towards a-adrenoceptor (a-AR), while pyrrolidin-2-one may effect on its selectivity towards a-AR subtypes.

   The obtained compounds were tested for their affinity for both a₁- and a₂-AR as well as for their in vitro activity in adrenaline induced arrhythmia and hypertension in rats.

^*This study is a subject of habilitation thesis entilted „Stuktury hybrydowe pirolidyn-2-onów i aryloalkilopiperazyn o potencjalnej aktywności biologicznej/krążeniowej”; Wydawnictwo Medycyna Praktyczna, Kraków 2009.

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