Effect of methoxy substitution on the adrenergic activity of three structurally related alpha 2-adrenoreceptor antagonists

We have recently reported the synthesis and alpha 2-antagonist activity of the methoxy derivative 2 [2-(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline] and described the enhanced potency of this compound over the parent 1,4-benzodioxan, idazoxan, in reversing the inhibition caused by alpha 2-adrenore...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1986-09, Vol.29 (9), p.1780-1783
Main Authors: Stillings, M R, England, C D, Welbourn, A P, Smith, C F
Format: Article
Language:English
Subjects:
Adrenergic alpha-Antagonists - pharmacology
Animals
Chemical Phenomena
Chemistry
Clonidine - antagonists & inhibitors
Dioxanes - pharmacology
Dioxins - pharmacology
Imidazoles - pharmacology
Male
Mice
Muscle Contraction - drug effects
Phenylephrine - antagonists & inhibitors
Piperidines - pharmacology
Piperoxan - pharmacology
Rats
Rats, Inbred Strains
Receptors, Adrenergic, alpha - drug effects
Receptors, Adrenergic, alpha - physiology
Structure-Activity Relationship
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Summary:We have recently reported the synthesis and alpha 2-antagonist activity of the methoxy derivative 2 [2-(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline] and described the enhanced potency of this compound over the parent 1,4-benzodioxan, idazoxan, in reversing the inhibition caused by alpha 2-adrenoreceptor agonists of the electrically induced twitch in the rat or mouse vas deferens. It was of interest to us to discover whether a similar substitution in the structurally related alpha 2-adrenoreceptor antagonists piperoxan, prosympal, and fenmetazole would similarly enhance potency. We subsequently discovered that this was not so and potency was decreased markedly. In particular, that of the methoxy derivative of piperoxan was ca. 220 times less than the parent structure.
ISSN:0022-2623