, 1997) it remains a major source of morbidity and mortality in developed countries. For example, between 0.5 and 1 million North Americans and Europeans die each year because of sudden cardiac death, which corresponds to 10–20% of all deaths among adults in the Western

world (Goldberger et al., 2008; Huikuri et al., 2001; Kromhout, 2007). In the past decade, the treatment of arrhythmia has been dramatically altered by the development of nonpharmacological therapies, such as targeted ablation of arrhythmogenic tissues and implantable JSH-23 cardioverter defibrillators (ICDs), as well as the limited efficacy and proarrhythmic potential of conventional antiarrhythmic (AA) drugs (Estrada and Darbar, 2008). AA drugs have been classified by Vaughan Williams mainly based PRN1371 order on their effects on cardiac action potentials into classes I–IV and later correlated to their effects on Na+ channel, β-receptors, and K+ and Ca2+ channels (Hashimoto, 2007; Vaughan Williams, 1992). In the course of our studies directed to search for new α1-AR antagonists, among which a series of (4-arylpiperazin-1-yl)propylpyrrolidin-2-one

or 3-alkyl-3-phenylpyrrolidin-2-one derivatives, it was shown that the compounds obtained also showed marked AA and Savolitinib clinical trial hypertensive activities. The ED50 values determined for a number of them was lower than or comparable with the reference compounds (Kulig et al., 2003, 2004, 2007, 2009; Malawska et al., 2002, 2005). For a large number of chemometric analyses reported in medical research, there are relatively few studies on the application of QSAR analysis to AA species (Debnath et al., 2003; Fumagalli et al., 2005; Pallavicini et al., 2006; Turabekova et al., 2008). In this context, the aim of this study, being a part of our drug design project, is to find a model explaining the Smoothened AA activity of a series of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one derivatives applying the quantitative relationship between structural parameters and AA activity. The quantitative structure–activity relationship (QSAR) equation for our

compounds is presented and discussed. Computational methods 1-[3-(4-Arylpiperazin-1-yl)propyl]pyrrolidin-2-one derivatives Thirty-three analogs of 1-[3-(4-(aryl)piperazin-1-yl)propyl]pyrrolidin-2-one were chosen from the reports published by us between 2002 and 2009 (Kulig et al., 2003, 2004, 2007, 2009; Malawska et al., 2002, 2005). The source publications concern the synthesis of over 70 arylpiperazine derivatives and their pharmacological test results. About 20 of these compounds display a lack of α1-ARs activity and 40 compounds display a lack of AA activity. These compounds are considered to be irrelevant for the model formulation and they were excluded from the current study. Thus, the set of the remaining 33 compounds displaying both α1-ARs and AA activity are appropriate for a QSAR analysis and are listed in Table 1.