Linked Life Data

6115057

Source:http://linkedlifedata.com/resource/pubmed/id/6115057

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1981-10-25
pubmed:abstractText
Propranolol (Inderal; 1) is extensively metabolized in man. Metabolites of interest pharmacologically include ring-hydroxylated propranolols (1a-g). In order to identify these ring-oxidized products and to study the effect of hydroxyl position on biological activity, we have synthesized all seven isomers. With the exception of 1b and 1g, the desired compounds were prepared by alkylation of the respective methoxy-1-naphthols with epichlorohydrin and reaction of the resulting epoxide with isopropylamine. Cleavage og the methyl group in fused pyridine hydrochloride afforded 1a,c-f. 1g was prepared by the direct alkylation of 1,8-naphthalenediol (17) with epichlorohydrin, followed by reaction with isopropylamine. 1b was synthesized by treating 2-naphthol (9) with chlorine gas and then treating the resulting 1,1-dichloronaphthalen-2(1H)-one (10) with sodium allyl oxide. Acetylation of the hydroxy function and epoxidatrion of the allyl group, followed by relation with isopropylamine, gave 3'-hydroxy-4'-chloropropranolol (15). Dechlorination gave 1b. All of the racemic hydroxylated propranolols produced beta blockade and direct vasodilation in anesthetized dogs. The potency is strongly dependent upon the position of the hydroxyl group, i.e., 1e is 4 times as potent as 1 as a beta receptor antagonist, whereas 1a, 1b, and 1g are all significantly less potent than 1. For direct vasodilation, 1a and 1g are equipotent to 1, while 1b-f are much less potent. The potencies of the compounds were also compared with their 1-octanol/pH 7.4 buffer distribution coefficients; the direct vasodilating potency was found to increase with increasing lipophilicity, while the beta-adrenergic antagonist potency decreased.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
309-14
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1981
pubmed:articleTitle
Ring-hydroxylated propranolol: synthesis and beta-receptor antagonist and vasodilating activities of the seven isomers.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.