Phenyl-substituted N-6-phenyladenosines and N-6-phenyl-5 '-N-ethylcarboxamidoadenosines with high activity at human adenosine A(2B) receptors

A series of phenyl-substituted N-6-phenyladenosines and N-6-phenyl-5'-N-eth ylcarboxamidoadenosines were synthesized and tested at adenosine receptor s ubtypes. EC50 values were determined for cyclic AMP production in CHO cells expressing human A(2B) receptors. Binding affinities were determined for r at A(1) and A(2A) receptors and human A(3) receptors. N-6-phenyladenosine d isplayed an EC50 value at A(2B) receptors of 6.3 mu M. Several N-6-phenylad enosine derivatives were more active than N-6-phenyladenosine, while two an alogs were also more potent than 5'-N-ethylcarboxamidoadenosine (NECA, 0.76 mu M), i.e., the -4-iodophenyl (10, 0.37 mu M) and the 4-aminosulfonylphen yl (20, 0.44 mu M) derivatives. N-6-phenyl-NECA derivatives were as active as their analogous adenosine derivatives. Drug Dev. Res. 49:85-93, 2000. (C ) 2000 Wiley-Liss, Inc.