Synthesis and Adrenoreceptor Blocking Action of Aziridinium Ions Derived from Phenoxybenzamine and Dibenamine

James G. Henkel, Philip S Portoghese, Jack W. Miller, Patricia Lewis

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18 Scopus citations

Abstract

Crystalline perchlorate salts of aziridinium ions derived from phenoxybenzamine and dibenamine were prepared. Both aziridinium ions were tested on the rat vas deferens and found to possess -adrenergic potencies which were nearly identical with those of the parent compounds. The hydrolysis rates of phenoxybenzamine and dibenamine aziridinium ions (2a,b) in physiological medium were found to be 6.04 × 10-4 and 8.35 × 10-4 sec-1, respectively. The rates of cyclization of the parent amines to 2a and 2b in aqueous medium were 1.9 × 10-2 and 7.2 × 10-3 sec-1, respectively. The potencies and kinetic profiles indicate that the aziridinium ion is the only active species in α-adrenergic blockade. Moreover, differences in potency between phenoxybenzamine and dibenamine appear to be exclusively to a difference in receptor affinity rather than to a difference in intrinsic alkylating ability.

Original languageEnglish (US)
Pages (from-to)6-10
Number of pages5
JournalJournal of medicinal chemistry
Volume19
Issue number1
DOIs
StatePublished - Jan 1 1976

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