Studies on New β-Adrenergic Blocking Agents. I. Syntheses and Pharmacology of Coumarin Derivatives

Abstract

Several (2-hydroxy-3-aminopropoxy) coumarin derivatives were synthesized from 5-, 7- and 8-hydroxycoumarin derivatives by established methods and β-adrenergic blocking activity was examined. A systematic study of the positional isomers in the coumarin derivatives showed that 5-methyl-8-(2-hydroxy-3-t-butylaminopropoxy) coumarin (XXIIa₂) was most favorable as a β-adrenergic blocking agent. It was shown that the classical structure requirement prevailed, but 7-positional isomer was much less active. Resolution of XXIIa₂ revealed that the 1-isomer possessed the major activity.