Structure-basicity and structure-affinity relationships of beta-adrenergic blocking agents

Abstract

pKa's of fourteen beta-receptor blockers, isoproterenol and norepinephrine, were determined potentiometrically. A Hammett analysis indicated that the influence of ring substituents on the basicity of the amines is attenuated by the ethanolic chain and abolished by the propranoloxy chain of beta-receptor blockers. The effect of ring substituents in phenoxypropranolamines upon affinity for the beta-adrengeric receptors is therefore unrelated to the strength of the bases. Two alterantive hypotheses are fowarded to explain why phenoxypropranolamines have greater affinities for the beta-receptors than phenethanolamines.