Ribose-modified adenosine analogs as adenosine receptor agonists

Abstract

Analogues of the potent adenosine receptor agonist (R)-N-(1-methyl-2-phenylethyl)adenosine (R-PIA), modified at N9, were prepared and evaluated for adenosine A1 and A2 receptor binding and in vivo central nervous system and cardiovascular effects. The modifications of N9 include deoxy sugars, 5''-substituted-5''-deoxyriboses, non-ribose sugars, sugar ring homologues, and acylic sugar analogue. Most of the derivatives have poor affinity for adenosine receptors. Only minor modifications at C5'' and C3'' maintain potent binding. In general, those derivatives exhibiting in vivo behavioral or cardiovascular effects also have the highest affinity for adenosine receptors.