New 2-arylpyrazolo[4,3-c]quinoline derivatives as potent and selective human A3 adenosine receptor antagonists.

In this paper we report the synthesis and biological evaluation of a new class of 2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-4-ones as A(3) adenosine receptor antagonists. We designed a new route based on the Kira-Vilsmeier reaction for the synthesis of this class of compounds. Some of the synthesized compounds showed A(3) adenosine receptor affinity in the nanomolar range and good selectivity as evaluated in radioligand binding assays at human (h) A(1), A(2A), A(2B), and A(3) adenosine receptor subtypes.

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.

Design, synthesis, and biological evaluation of new 8-heterocyclic xanthine derivatives as highly potent and selective human A2B adenosine receptor antagonists.

Here we report the synthesis of 8-heterocycle-substituted xanthines as potent and selective A(2B) adenosine receptor antagonists. The structure-activity relationships (SAR) of the xanthines synthesized in binding to recombinant human A(2B) adenosine receptors (ARs) in HEK-293 cells (HEK-A(2B)) and at other AR subtypes were explored. The synthesized compounds showed A(2B) adenosine receptor affinity in the nanomolar range and good levels of selectivity evaluated in radioligand binding assays at human (h) A(1), A(2A), A(2B), and A(3) ARs.