Synthesis and Binding to β‐Adrenergic Receptors of p‐Aminobenzyl Analogues of Practolol and Atenolol

Abstract

The p‐aminobenzyl analogues (8a and 8b, respectively) of the cardioselective β‐adrenergic receptor antagonists practolol and atenolol were prepared from the corresponding phenoxymethyloxiranes in 30 and 13% yields, respectively. The dissociation constants for the β‐adrenergic receptor were measured in membrane preparations of rat heart and lung, in membranes from the heart (which contain mostly β1‐adrenergic receptors), the affinities of the derivatives and parent compounds were similar. By contrast, in membranes from the lung (which contain mostly β2‐adrenergic receptors), the derivatives were more potent than the parent compounds. Thus, the cardioselectivities of the p‐aminobenzyl analogues 8a and 8b were about one‐sixth those of the respective parents.