Document Detail

Salicylamide derivatives related to medroxalol with alpha- and beta-adrenergic antagonist and antihypertension activity.
MedLine Citation:
PMID:  6115059     Owner:  NLM     Status:  MEDLINE    
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. One of the analogues in which the aralkylamine side chain of 1 was replaced by a fragment of a known alpha-adrenergic receptor blocker, 2-hydroxy-5-[1-hydroxy-2-[4-(2-methylphenyl)-1-piperazinyl]ethyl]benzamide (22), showed an interesting pharmacologic profile of potential therapeutic usefulness.
J M Grisar; G P Claxton; T M Bare; R C Dage; H C Cheng; J K Woodward
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  24     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1981 Mar 
Date Detail:
Created Date:  1981-10-25     Completed Date:  1981-10-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  327-36     Citation Subset:  IM    
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MeSH Terms
Adrenergic alpha-Antagonists*
Adrenergic beta-Antagonists*
Antihypertensive Agents*
Blood Pressure / drug effects
Ethanolamines / pharmacology*
Salicylamides / pharmacology*
Structure-Activity Relationship
Reg. No./Substance:
0/Adrenergic alpha-Antagonists; 0/Adrenergic beta-Antagonists; 0/Antihypertensive Agents; 0/Ethanolamines; 0/Salicylamides; 56290-94-9/medroxalol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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