Quantitative evaluation of the β2-adrenoceptor affinity of phenoxypropanolamines and phenylethanolamines

Article abstract of DOI:10.1021/jm00147a037

The influence of the aromatic moiety of β-adrenoceptor ligands on the affinity for the β₂-adrenoceptor has been studied. Three classes of ligands have been examined, viz. N-isopropyl- and N-tert-butylphenylethanolamines and N-isopropylphenoxypropanolamines. Computer-assisted analysis of the inhibition by any of these ligands of the specific (-)-[³H]dihydroalprenolol binding to the β₂-adrenoceptors of a bovine skeletal muscle preparation in the presence of GppNHp (10^-4 M) yielded the affinities of these ligands at pH 7.5. The obtained values were adjusted for the amounts of cations present at this pH value. A significant correlation was found between the calculated lipophilicities and the experimentally determined affinities in the three classes. Furthermore, steric factors seem to play an important role, as these correlations were improved by the introduction of steric parameters for the aromatic substituents in the regression analyses. From the established equations it is concluded that the phenoxypropanolamine derivatives bind to the β₂-adrenoceptor in a way different from that of the ligands in both ethanolamine classes.