C-2 FUNCTIONALIZED N6-CYCLOSUBSTITUTED ADENOSINES - HIGHLY SELECTIVE AGONISTS FOR THE ADENOSINE-A1-RECEPTOR

Synthesis of novel N6-cyclosubstituted isoguanosines and related C-2 functionalized compounds utilizing methodologies with key thermal radical and photochemical steps developed in our laboratory is described. Data on the affinities of these new compounds for the adenosine A1 and A2 receptors clearly show that a number of N6-cyclosubstituted isoguanosines show excellent A1 agonist activity with the best activity and selectivity being associated with five-membered ring mono- or bicyclic systems at the N6-position. Interestingly, 2-iodo-N6-cyclopentyladenosine also shows excellent A1 receptor binding and A2/A1 selectivity.