A series of 1,8-naphthyridine derivatives bearing various substituents in position 3, 4, and 7 of the heterocyclic nucleus have been synthesized and evaluated for their affinity at the bovine and human adenosine receptors. The new compounds were found to lack the affinity toward A(1)AR, whereas many of them are able to acquire an interesting affinity and selectivity for the A(2A)AR.