Synthesis, Biological and Modeling Studies of 1,3‐Di‐n‐propyl‐2,4‐dioxo‐6‐methyl‐8‐(substituted) 1,2,3,4‐Tetrahydro[1,2,4]‐triazolo[3,4‐f]‐purines as Adenosine Receptor Antagonists.

Abstract A new series of potential adenosine receptor antagonists with a [1,2,4]-triazolo-[3,4-f]-purine structure bearing at the 1 and 3 position n-propyl groups have been synthesized, and their affinities at the four human adenosine receptor subtypes (A1, A2A, A2B and A3) have been evaluated. In this case the presence of n-propyl groups seems to induce potency at the A2A and A3 adenosine receptor subtypes as opposed to our previously reported series bearing methyl substituents at the 1 and 3 positions. In particular the non-acylated derivative 17 showed affinity at these two receptor subtypes in the micromolar range. Indeed, preliminary molecular modeling investigations according to the experimental binding data indicate a modest steric and electrostatic antagonist-receptor complementarity.