4‐amino‐6‐alkyloxy‐2‐alkylthiopyrimidine derivatives as novel non‐nucleoside agonists for the adenosine A 1 receptor

Three 4‐amino‐6‐alkyloxy‐2‐alkylthiopyrimidine derivatives ( 4 – 6 ) were investigated as potential non‐nucleoside agonists at human adenosine receptors ( AR s). When tested in competition binding experiments, these compounds exhibited low micromolar affinity ( K i values comprised between 1.2 and 1.9  μ m ) for the A 1 AR and no appreciable affinity for the A 2A and A 3 AR s. Evaluation of their efficacy profiles by measurement of intracellular cAMP levels revealed that 4 and 5 behave as non‐nucleoside agonists of the A 1 AR with EC 50 values of 0.47 and 0.87  μ m , respectively. No clear concentration‐response curves could be instead obtained for 6 , probably because this compound modulates one or more additional targets, thus masking the putative effects exerted by its activation of A 1 AR . The three compounds were not able to modulate A 2B AR ‐mediated cAMP accumulation induced by the non‐selective AR agonist NECA , thus demonstrating no affinity toward this receptor.