Activity of N-(phenethyl)phenylethanolamines at beta(1) and beta(2) adrenoceptors: Structural modifications can result in selectivity for either subtype

A series of phenylethanolamines bearing a 2-[1-phenylpropyl] substituent on the nitrogen atom was evaluated in vitro for activity at beta (1)- and bet a (2)-adrenoceptors. As previously observed, the presence of 3,4-dihydroxy substitution on phenylethanolamine is required for potent activation of bot h subtypes, whereas the 3,5-dihydroxy analog showed selectivity for the bet a (2)-subtype. Replacement by a carboxyl group of the 4-hydroxyl group on t he aralkyl nitrogen substituent produced only a small reduction in beta (1) potency (5-fold), whereas beta (2) potency was reduced by more than 100-fo ld. Hence this structural class includes agonists having either a beta (1), nonselective beta (1)/beta (2) or beta (2) Selectivity profile. Copyright (C) 2001 S. Karger AG, Basel.