Linked Life Data

3735308

Source:http://linkedlifedata.com/resource/pubmed/id/3735308

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1986-9-17
pubmed:abstractText
The syntheses of seven 4-(substituted phenyl)but-2-en(or yn)yl quaternary ammonium salts and four related tertiary amines are described. The Meerwein arylation reaction was the preferred synthetic method for the required intermediate 1-aryl-4-halo-2-butenes (15a-c, 18). In the case of 18, the trans stereochemistry of the Meerwein adduct of 2,3-dimethylbutadiene was established unambiguously by 2D NMR and X-ray studies. The title compounds represent conformationally restricted analogues of the class III antiarrhythmic agent clofilium (1) and exhibit comparable potency and efficacy in the in vitro evaluation using isolated canine Purkinje fibers. These results suggest that the alkylene chain in 1 is extended in the active conformation. Computer-aided conformational analysis (MM2) supports this conclusion. Selective catalytic hydrogen conditions were developed for the conversion of the unsaturated analogue 2 to clofilium (1) with minimal hydrogenolysis of the allylic quaternary ammonium moiety, thus completing a novel and efficient synthesis of this substance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1398-405
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Synthesis and class III antiarrhythmic activity of (phenylbut-2-enyl)ammonium salts. Effect of conformation on activity.
pubmed:publicationType
Journal Article