Jan 1, 1976

Synthesis and adrenoreceptor blocking action of aziridinium ions derived from phenoxybenzamine and dibenamine

Journal of Medicinal Chemistry
J G HenkelP Lewis

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 alpha-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 6.0 4 x 10(-4) and 8.35 x 10(-4) sec-1, respectively. The rates of cyclization of the parent amines to 2a and 2b in aqueous medium were 1.9 x 10(-2) and 7.2 x 10(-3) sec-1, respectively. The potencies and kinetic profiles indicate that the aziridinium ion is the only active species in alpha-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.

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Mentioned in this Paper

Amines
Phenoxybenzamine Hydrochloride
Azirines
Smooth Muscle
Adrenergic alpha-Antagonists
Adrenergic Receptor
Cyclization
Inotropism
Crystal Structure
Vas Deferens Structure

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