Evaluation of lipophilicity of piperazine derivatives by thin layer chromatography and principal component analysis

The lipophilic character of a series of active anticonvulsant N-substituted amides of alpha-piperazine-gamma-hydroxybutyric was studied. The classical R-Mo- values were measured by means of reversed thin layer chromatography using a mixture of methanol, TRIS buffer, and acetic acid as the solvent sy stem and compared with the factors scores obtained by principal component a nalysis based also on the TLC retention data. The significant correlation b etween the R-Mo- values and slopes (the specific hydrophobic surface areas) usually indicated that this group of N-substituted amides could be conside red as a homologous series of compounds independent of their structural het erogeneity. It is emphasized, once again, that this procedure can not be a rational and objective way for congeneric studies because there is always a high correlation between slope and intercept. The reliability of the facto r scores values as lipophilicity indices is shown by their high correlation with the classical R-Mo-values. In addition, the "lipophilicity chart" des cribed by the first two components will have the effect of separating compo unds from each other most effectively from the congeneric aspect point of v iew. Finally, a better correlation was observed between scores corresponding to the first principal component and the partition coefficients (log P) of the amides, calculated by using the Prolog P module of the Pallas system.