Comparison of Chromatographically Determined Values of the Lipophilicity of Anticonvulsant Active N-substituted Amides of a-Arylalkylamine-gamma-hydroxybutyric Acid with Values Estimated by Computational Methods

摘要

The lipophilicity of five series of anticonvulsant active N-substituted amides of alpha-arylalkylamine-gamma-hydroxybutyric acid (compounds 1-37) has been investigated. The lipophilicity of nine N-substituted amides of alpha-arylalkylamine-gamma-hydroxybutyric acid was determined by reversed-phase thin-layer chromatography (RPTLC) using mixtures of methanol, pH 7.4 Tris buffer, and acetic acid as mobile phases. Mobile-phase methanol concentrations were in the range 25-65%. The R_M values of the compounds investigated were linearly dependent on methanol concentration. Partition coefficients (log P) were calculated for all the compounds by means of the software Prolog P (Pallas) and SciLogP (Alchemy 2000), and compared with the relative lipophilicity (R_(M0)). It was found that log P values estimated by SciLogP correlated better with values obtained by TLC, and thus the methodology of Bodor and co-workers based on the use of molecular properties method for calculation of partition coefficients was a better tool for preliminary determination of the lipophilicity of the compounds investigated.