PMID: 6115059Mar 1, 1981Paper

Salicylamide derivatives related to medroxalol with alpha- and beta-adrenergic antagonist and antihypertension activity

Journal of Medicinal Chemistry
J M GrisarJ K Woodward


Analogues of medroxalol (1) were prepared in which the carboxamide function, the phenolic hydroxy group, and the aralkylamine side chain were modified. N-alkyl-substituted amide analogues of 1 showed diminishing beta-blocking activity with increasing steric bulk of the alkyl group. This allowed the conclusion that deactivation of the phenolic hydroxy group of 1 by the carbonyl group of the amide function is responsible for the beta-adrenergic antagonistic properties of 1. This conclusion was strengthened by the finding that the phenolic O-methyl analogue 5-[2-[[3-(1,3-benzodioxol-5-yl)-1-methylpropyl]amino]-1hydroxyethyl]-2-methoxybenzamide (13) was found to have enhanced beta-adrenergic blocking activity. The finding that 13 also had decreased alpha-blocking activity compared to 1 indicated that the phenolic hydroxy group of 1 enhances alpha-adrenergic antagonism. The finding that 1 and 13 showed such a large difference in relative alpha- to beta-blocking potency while exhibiting approximately equal antihypertensive activity in spontaneously hypertensive rats was surprising. In indicated that pharmacologic properties other than alpha- and beta-adrenergic blockade may contribute to the antihypertensive activity of medroxalol. O...Continue Reading


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Related Concepts

Medroxalol monohydrochloride, (S-(R*, S*))-isomer
Adrenergic alpha-Antagonists
Adrenergic beta-Antagonists
Antihypertensive Agents
Diastolic Blood Pressure
Canis familiaris
Structure-Activity Relationship

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