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

A series of novel N6-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 5b11 displayed the highest activity with an IC50 value of 29 ± 3 μM. Furthermore, five compounds were tested against arachidonic acid (AA)-induced human platelet aggregation. The results showed that compound 5b10 exhibited the highest activity with an IC50 value of 3 ± 2 μM. The adenosine derivatives substituted with a phenethyl group at the N6 position and a methylthio or ethylthio group at the C-2 position displayed high antiplatelet aggregation activity.

A series of novel N6-alkyl(aryl)-2-alkyl(aryl)thioadenosines were synthesized and evaluated for their human antiplatelet activities.Figure optionsDownload as PowerPoint slideHighlights
► A series of novel N6-alkyl(aryl)-2-alkyl(aryl)thioadenosines were synthesized.
► Their human antiplatelet activities were also evaluated.
►  Compounds 5b10 and 5b11 showed excellent antiplatelet activity.
► The structure–activity relationships of these novel compounds have been discussed.