New pyrrolo[2,1-f]purine-2,4-dione and imidazo[2,1-f]purine-2,4-dione derivatives as potent and selective human A3 adenosine receptor antagonists.

Compounds presenting an additional fused ring on the xanthine nucleus have been reported to exhibit antagonistic activity with various levels of affinity and selectivity toward the four adenosine receptors subtypes A(1), A(2A), A(2B), and A(3). This paper reports synthesis and biological evaluation of new 1-benzyl-3-propyl-1H,6H-pyrrolo[2,1-f]purine-2,4-diones and 1-benzyl-3-propyl-1H,8H-imidazo[2,1-f]purine-2,4-diones, among which we identified potent and selective A(3) adenosine receptors antagonists. In particular, 1-benzyl-7-methyl-3-propyl-1H,8H-imidazo[2,1-f]purine-2,4-dione (11e) shows a K(i) (hA(3)) value from binding assay of 0.8 nM.