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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
1998-4-9
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pubmed:abstractText |
Among the recently reported 2-(ar)alkynyl derivatives of 5'-N-ethylcarboxamidoadenosine (NECA), the (R,S)-2-(3-hydroxy-3-phenyl-1-propyn-1-yl)NECA [(R,S)-PHPNECA or SCH 59761] was found to be a very potent agonist at A1 and A2A receptor subtypes, with a Ki of 2.5 nM and 0.9 nM, respectively. Furthermore, this compound showed an inhibitory activity on platelet aggregation 16-fold higher than NECA, being the most potent anti-aggregatory nucleoside reported so far. Since this compound bears a chiral carbon in the side chain, the diastereoisomer separation was undertaken both by chiral HPLC and by a stereospecific synthetic method. Binding assays have shown that the (S)-diastereomer is about fivefold more potent and selective than the (R)-diastereomer as agonist of the A2A receptor subtype [(S)-PHPNECA, KiA2A = 0.5 nM; (R)-PHPNECA, KiA2A = 2.6 nM]. Functional studies indicated that (S)-PHPNECA possesses marked vasodilating activity and produces a relevant decrease in heart rate. Moreover, the (S)-diastereomer proved to be about ten times more potent than the (R)-diastereomer in inducing cardiovascular effects, in in vivo hemodynamic studies. However, the greatest difference between these two enantiomers resulted in the platelet aggregation test: in fact, the (R)-diastereomer displayed an inhibitory activity similar to that of NECA, whereas the (S)-diastereomer was 37-fold more active than NECA as an inhibitor of rabbit platelet aggregation, induced by ADP. These data suggest that (S)-PHPNECA could be a useful tool to investigate the mode of binding of agonists to the platelet adenosine receptor subtype.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0968-0896
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2267-75
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:9459024-Adenosine,
pubmed-meshheading:9459024-Animals,
pubmed-meshheading:9459024-Blood Pressure,
pubmed-meshheading:9459024-Chromatography, High Pressure Liquid,
pubmed-meshheading:9459024-Heart Rate,
pubmed-meshheading:9459024-Male,
pubmed-meshheading:9459024-Models, Molecular,
pubmed-meshheading:9459024-Platelet Aggregation,
pubmed-meshheading:9459024-Platelet Aggregation Inhibitors,
pubmed-meshheading:9459024-Purinergic P1 Receptor Agonists,
pubmed-meshheading:9459024-Rabbits,
pubmed-meshheading:9459024-Rats,
pubmed-meshheading:9459024-Rats, Inbred SHR,
pubmed-meshheading:9459024-Rats, Sprague-Dawley,
pubmed-meshheading:9459024-Stereoisomerism
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pubmed:year |
1997
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pubmed:articleTitle |
Adenosine receptor agonists: synthesis and biological evaluation of the diastereoisomers of 2-(3-hydroxy-3-phenyl-1-propyn-1-yl)NECA.
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pubmed:affiliation |
Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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