Synthesis of N6-alkyl(aryl)-2-alkyl(aryl)thioadenosines as antiplatelet agents.

A series of novel N(6)-alkyl(aryl)-2-alkyl(aryl)thioadenosines were synthesized, and their human antiplatelet aggregation activities were evaluated by the stimulation of adenosine 5'-diphosphate (ADP). Some of these compounds showed strong activity, among which compound 5b(11) displayed the highest activity with an IC(50) value of 29 ± 3 μM. Furthermore, five compounds were tested against arachidonic acid (AA)-induced human platelet aggregation. The results showed that compound 5b(10) exhibited the highest activity with an IC(50) value of 3 ± 2 μM. The adenosine derivatives substituted with a phenethyl group at the N(6) position and a methylthio or ethylthio group at the C-2 position displayed high antiplatelet aggregation activity.