A series of new 2-alkynyl, 2-cycloalkynyl, and 2-aralkynyl derivs. of adenosine-5'-ethyluronamide (NECA) were evaluated in binding studies and functional assays to assess their potency and selectivity at A2 vs. A1 receptors. The new derivs. were also tested as inhibitors of rabbit platelet aggregation induced by ADP. While the presence of an arom. or heteroarom. ring conjugated to the triple bond decreased antiplatelet activity, the introduction of a hydroxyl group or a heterocyclic ring on the alkynyl side chain increased the antiaggregatory activity in comparison with NECA, resulting in the most potent inhibitors of platelet aggregation so far known in the nucleoside series. However, the presence of an α-quaternary carbon markedly reduced the antiaggregatory potency without affecting the A2 binding affinity, suggesting that the platelet receptor is not a typical A2a site.

Platelet aggregation inhibitory activity of selective A2 adenosine receptor agonists.

CRISTALLI, Gloria;VITTORI, Sauro;VOLPINI, Rosaria
1995-01-01

Abstract

A series of new 2-alkynyl, 2-cycloalkynyl, and 2-aralkynyl derivs. of adenosine-5'-ethyluronamide (NECA) were evaluated in binding studies and functional assays to assess their potency and selectivity at A2 vs. A1 receptors. The new derivs. were also tested as inhibitors of rabbit platelet aggregation induced by ADP. While the presence of an arom. or heteroarom. ring conjugated to the triple bond decreased antiplatelet activity, the introduction of a hydroxyl group or a heterocyclic ring on the alkynyl side chain increased the antiaggregatory activity in comparison with NECA, resulting in the most potent inhibitors of platelet aggregation so far known in the nucleoside series. However, the presence of an α-quaternary carbon markedly reduced the antiaggregatory potency without affecting the A2 binding affinity, suggesting that the platelet receptor is not a typical A2a site.
1995
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/241529
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact