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

Abstract

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

Citations

Jan 1, 2008·Acta Crystallographica. Section E, Structure Reports Online·Jiang KeLi Fei
Jan 1, 1984·Clinical and Experimental Hypertension. Part A, Theory and Practice·A A Hancock
Oct 1, 1988·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·H Benveniste, N H Diemer
Sep 1, 1984·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·R P SimonB S Meldrum
Aug 1, 1984·The Journal of Pharmacy and Pharmacology·T TakenakaN Inukai
Nov 22, 2020·Organic & Biomolecular Chemistry·Anamarija KneŽevićMarijana Vinković

Related Concepts

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

Related Feeds

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.