8-Substituted-9-deazaxanthines as adenosine receptor ligands: design, synthesis and structure-affinity relationships at A2B.

A number of 8-substituted-9-deazaxanthine derivatives (1,3-dialkyl-6-substituted-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-diones) were prepared and tested for their antagonistic activity at the recombinant human adenosine receptors, in particular at the A(2B) and A(2A) receptor subtypes. Compounds endowed with micromolar to nanomolar binding affinities, but with poor A(2B)/A(2A) selectivity, were obtained. Preliminary quantitative structure-affinity relationships suggested that the binding potency at the A(2B) receptor is mainly modulated by the electronic and lipophilic properties of the ligands.