Quantitative evaluation of the .beta.2-adrenoceptor affinity of phenoxypropanolamines and phenylethanolamines

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Abstract
The influence of the aromatic moiety of .beta.-adrenoceptor ligands on the affinity for the .beta.2-adrenoceptor was studied. Three classes of ligands were examined, i.e., 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 .beta.2-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 the pH value. A significant correlation was found between the calculated lipophilicities and the experimentally determined affinities in the 3 classes. 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. The established equations indicate that the phenoxypropanolamine derivatives bind to the .beta.2-adrenoceptor in a way different from that of the ligands in both ethanolamine classes.

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