Influence of Lipophilicity and Chirality on the Selectivity of Ligands for β1- and β2-Adrenoceptors

Abstract

Abstract Eudismic and QSAR analyses are reported for the β1- and β2-adrenoceptor affinities and β1-selectivity of 10 enantiomeric pairs of ligands with only N-isopropyl or N-t-butyl groups. For both receptors, the eudismic index (ratio of affinity) increases with the affinity of the eutomers. However, the affinity of the distomers for the β2-adrenoceptor is relatively high, suggesting additional hydrophobic interactions. This is confirmed by various correlations between affinities and lipophilicities, showing that the affinity for β2-adrenoceptors is slightly more dependent on lipophilicity than that for β1-adrenoceptors. As a result, the β1-selectivity of the investigated β1-adrenoceptor ligands is strongly and negatively correlated with their lipophilicity (r = −0.942).