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• W1998187415 abstract "An association between α1-adrenoceptor affinities, hERG K+-antagonistic properties and antiarrhythmic activities for a series of phenylpiperazine derivatives of hydantoin (2a–21a) was investigated. New compounds were synthesized and tested for their affinity for α1-adrenoceptors in radioligand binding assay using [3H]-prazosin as a selective radioligand. Antiarrhythmic activities in adrenaline- and barium chloride-induced arrhythmia models, an influence of the phenylpiperazine derivatives on the ECG-components and blood pressure were tested in vivo in normotensive rats. The hERG K+-antagonistic properties of the most potent antiarrhythmic agents were investigated in silico by the use of program QikProp. The highest α1-adrenoceptor affinity (Ki = 4.7 nM) and the strongest antiarrhythmic activity in adrenaline induced arrhythmia (ED50 = 0.1 mg/kg) was found for 1-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione hydrochloride (19a). The results indicated a significant correlation between α1-AR affinities (pKi) and antiarrhythmic activity (ED50) in adrenaline model (R2 = 0.92, p <0.005). Influence of the examined phenylpiperazine hydantoin derivatives on hERG K+ channel, predicted by means of in silico methods, suggested their hERG K+-blocking properties." @default.
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• W1998187415 date "2012-04-01" @default.
• W1998187415 modified "2023-10-14" @default.
• W1998187415 title "Antiarrhythmic properties of phenylpiperazine derivatives of phenytoin with α1-adrenoceptor affinities" @default.
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• W1998187415 doi "https://doi.org/10.1016/j.bmc.2012.02.009" @default.
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