8-Substituted-9-deazaxanthines as adenosine receptor ligands: design, synthesis and structure-affinity relationships at A 2B

Abstract

A number of 8-substituted-9-deazaxanthine derivatives (1,3-dialkyl-6-substituted-1 H-pyrrolo[3,2- d]pyrimidine-2,4(3 H,5 H)-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.