Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands
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Kostić Rajačić, Slađana
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Reversed-phase thin-layer chromatography and micellar thin-layer chromatography were used in order to investigate retention behaviour and to determine lipophilicity of series of 2(methoxy)phenylpiperazine dopamine D2 ligands with different size, shape and rigidity. The retention mechanism was discussed. The lipophilicity parameters obtained in conventional reversed-phase systems expressed as RM0 and C0, as well as RM values determined in microemulsion reversed-phase systems were correlated with in silico determined lipophilicity values. In silico pharmacokinetic properties of 2-(methoxy)phenylpiperazine dopamine D2 ligands revealed the importance of experimentally determined lipophilicity values besides the molecular weight, on the blood–brain barrier permeability process. Also, the experimentally determined lipophilicity was found as a very important factor in plasma protein binding process of 2-(methoxy)phenylpiperazine dopamine D2 ligands. Besides, the Lipinski's rule of five indic...ates that examined ligands satisfy the criterion of drug-like molecules. The principal component analysis was performed on the experimentally determined and calculated lipophilicity values as well on the molecular descriptors which describe the pharmacokinetic properties in order to provide basic insights into similarities among the studied ligands.
Keywords:2-(Methoxy)phenylpiperazine dopamine D2 ligands / Reversed-phase thin-layer chromatography (RPTLC) / Microemulsion thin-layer chromatography (METLC) / Lipophilicity / Blood–brain barrier (BBB) permeability / Protein binding capacity (QPlogKhsa)
Source:Journal of Chromatography B, 2019, 1124, 146-153