Similarities and differences in affinity and binding modes of tricyclic pyrimido- and pyrazinoxanthines at human and rat adenosine receptors.

•Design and synthesis of new tricyclic xanthine derivatives were performed.•Potent ligands of A1 adenosine receptors with nanomolar affinities were found.•Structure–activity relationship for the synthesized series was analyzed.•Comparison of binding modes at rat and human A2A and A1 ARs was performed.