Conformational analogs of dopamine. Synthesis and pharmacological activity of (E)- and (Z)-2-(3,4-dihydroxyphenyl)cyclopropylamine hydrochlorides

Abstract

(E)- and (Z)-(.+-.)-2-(3,4-dihydroxyphenyl)cyclopropylamine hydrochlorides were synthesized as part of a program to assess the importance of conformational isomerism with respect to the various peripheral biological actions of dopamine. Neither compound possessed dopaminergic activity in the canine renal blood-flow model but both agents were weak .alpha.-adrenergic agonists and exhibited cardiostimulatory properties similar to dopamine. The E-isomer was .apprx. 5 times more potent than the Z isomer in its .alpha.-adrenergic activity and .apprx. 15 times as potent in its cardiac effects. Possible reasons for the lack of renal dopaminergic activity exhibited by the E isomer are presented.