RP-TLC Determination of the Lipophilicity of 1-Substituted Pyrrolidin-2-one Derivatives. Correlation of Lipophilicity with Affinity for α-Adrenoceptors

The relative lipophilicity (RM0) of fourteen 1-substituted pyrrolidin-2-one derivatives has been measured by use of RP-TLC plates and mixtures of acetonitrile and pH 7.0 Tris buffer with volume fractions of acetonitrile between 20 and 80% were used as mobile phases. Retention data (RM) obtained by this method were exponentially dependent on acetonitrile concentration and enabled estimation of the relative lipophilicity corresponding to pH 7.0 Tris buffer as mobile phase. 1-{2-Hydroxy-3-[4-(3-methoxyphenyl)piperazin-1-yl]propyl}pyrrolidin-2-one had the highest relative lipophilicity (1.33) and butylcarbamic acid 1-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]-2-(2-oxopyrrolidin-1-yl)ethyl ester had the lowest (0.72). Comparison of RM0 values obtained with the affinity of the compounds tested for a-adrenoceptors enable formulation of preliminary equations for quantitative structure-activity relationships (QSAR).