2-Alkynyl derivatives of adenosine and adenosine-5'-N-ethyluronamide as selective agonists at A2 adenosine receptors

J Med Chem. 1992 Jun 26;35(13):2363-8. doi: 10.1021/jm00091a003.


In the search for more selective A2-receptor agonists and on the basis that appropriate substitution at C2 is known to impart selectivity for A2 receptors, 2-alkynyladenosines 2a-d were resynthesized and evaluated in radioligand binding, adenylate cyclase, and platelet aggregation studies. Binding of [3H]NECA to A2 receptors of rat striatal membranes was inhibited by compounds 2a-d with Ki values ranging from 2.8 to 16.4 nM. 2-Alkynyladenosines also exhibited high-affinity binding at solubilized A2 receptors from human platelet membranes. Competition of 2-alkynyladenosines 2a-d for the antagonist radioligand [3H]DPCPX and for the agonist [3H]CCPA gave Ki values in the nanomolar range, and the compounds showed moderate A2 selectivity. In order to improve this selectivity, the corresponding 2-alkynyl derivatives of adenosine-5'-N-ethyluronamide 8a-d were synthesized and tested. As expected, the 5'-N-ethyluronamide derivatives retained the A2 affinity whereas the A1 affinity was attenuated, resulting in an up to 10-fold increase in A2 selectivity. A similar pattern was observed in adenylate cyclase assays and in platelet aggregation studies. A 30- to 45-fold selectivity for platelet A2 receptors compared to A1 receptors was found for compounds 8a-c in adenylate cyclase studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Adenosine / metabolism
  • Adenosine / pharmacology*
  • Adenosine-5'-(N-ethylcarboxamide)
  • Adenylyl Cyclases / metabolism
  • Animals
  • Binding, Competitive
  • Blood Platelets / chemistry
  • Brain Chemistry
  • Cell Membrane / chemistry
  • Cells, Cultured
  • Humans
  • Platelet Aggregation / drug effects
  • Radioligand Assay
  • Rats
  • Receptors, Purinergic / drug effects*


  • Receptors, Purinergic
  • Adenosine-5'-(N-ethylcarboxamide)
  • Adenylyl Cyclases
  • Adenosine