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Synthesis and basic physicochemical properties of 1-[3-(Y-alkoxyphenylcarbamoyloxy)-2--hydroxypropyl]-4-(2-methylphenyl)piperazinium chlorides


Authors: Ivan Malík 1;  Eva Sedlárová 1;  Fils Andriamainty 1;  Jana Gališinová 1;  Jozef Csöllei 2;  Ján Vančo 2
Authors‘ workplace: Univerzita Komenského Bratislava, Farmaceutická fakulta, Katedra farmaceutickej chémie 1;  Veterinární a farmaceutická univerzita Brno, Farmaceutická fakulta, Ústav chemických léčiv 2
Published in: Čes. slov. Farm., 2011; 60, 137-143
Category: Original Articles

Overview

1-[3-(Y-Alkoxyphenylcarbamoyloxy)-2-hydroxypropyl]-4-(2-methylphenyl)piperazinium chlorides (labelled as 7a–7d) were prepared within a complex study of the relationships between the chemical structure, physicochemical properties and biological (antiarrhythmic, antihypertensive) activity of dual acting compounds. Chemical structures of basic forms (labelled as 7a2C–7d2C) and appropriate monochlorides (labelled as 7a–7d) were confirmed by 1H-NMR, 13C-NMR, MS and IR spectral and elemental analysis. The estimated physicochemical parameters included the melting point data, solubility profile in various media, purity checking (adsorption thin-layer chromatography), surface activity determination (Traube stalagmometric method), acidobasic characteristics (pKa value determination by alkalimetric titration) as well as the log ε values estimation by UV/VIS spectrophotometry. Other experimental values under consideration were lipohydrophilic characteristics using reversed-phase thin-layer chromatography (RM readouts) RP-HPLC (log k’ data) and the log Pexps estimated in octan-1-ol/phosphate buffer medium.

Key words:
dual acting α- and ß-blockers – N-phenylpiperazine – spectral characteristics – acidobasic properties – lipophilicity


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