Phenyl-substituted N6-phenyladenosines and N6-phenyl-5?-N-ethylcarboxamidoadenosines with high activity at human adenosine A2B receptors

Abstract

A series of phenyl-substituted N6-phenyladenosines and N6-phenyl-5′-N-ethylcarboxamidoadenosines were synthesized and tested at adenosine receptor subtypes. EC50 values were determined for cyclic AMP production in CHO cells expressing human A2B receptors. Binding affinities were determined for rat A1 and A2A receptors and human A3 receptors. N6-phenyladenosine displayed an EC50 value at A2B receptors of 6.3 μM. Several N6-phenyladenosine derivatives were more active than N6-phenyladenosine, while two analogs were also more potent than 5′-N-ethylcarboxamidoadenosine (NECA, 0.76 μM), i.e., the 4-iodophenyl (10, 0.37 μM) and the 4-aminosulfonylphenyl (20, 0.44 μM) derivatives. N6-phenyl-NECA derivatives were as active as their analogous adenosine derivatives. Drug Dev. Res. 49:85–93, 2000. © 2000 Wiley-Liss, Inc.