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

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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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Dibenzylchlorethamine
Phenoxybenzamine
Ions
Adrenergic Agents
Vas Deferens
Cyclization
Amines
Hydrolysis
Salts

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Synthesis and Adrenoreceptor Blocking Action of Aziridinium Ions Derived from Phenoxybenzamine and Dibenamine. / Henkel, James G.; Portoghese, Philip S; Miller, Jack W.; Lewis, Patricia.

In: Journal of Medicinal Chemistry, Vol. 19, No. 1, 01.01.1976, p. 6-10.

Research output: Contribution to journalArticle

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