2-Alkoxyadenosines: potent and selective agonists at the coronary artery A2 adenosine receptor

Authors:
  • RTRobert D. Thompson
    Robert D. Thompson
  • LALuis H. Arroyo
    Luis H. Arroyo
  • RORay A. Olsson
    Ray A. Olsson
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Abstract
A Langendorff guinea pig heart preparation served for the assay of agonist activity of a series of 24 2-alkoxyadenosines at the A1 and A2 adenosine receptors of, respectively, the atrioventricular node (conduction block) and coronary arteries (vasodilation). Activities are low at the A1 receptor and do not show a clear relationship to the size or hydrophobicity of the C-2 substituent. All the analogues are more potent at the A2 receptor, activity varying directly with the size and hydrophobicity of the alkyl group. The most potent analogue in this series, 2-(2-cyclohexylethoxy)adenosine has an EC50 of 1 nM for coronary vasodilation and is 8700-fold selective for the A2 receptor.