Synthesis and pharmacological screening of new 2-methylthio/2-methanesulfonyl/2-methoxy-5H-[1]benzopyrano[4,3-d]pyrimidines were planned in order to study the effects of the 5-substitution with alkoxy/phenoxy/alkylthio and phenylthio groups both on in vitro antiplatelet and in vivo antinociceptive activities. Antiplatelet activity was assessed in vitro against ADP, Arachidonic acid and U46619 induced aggregation, in rabbit plasma. Anti-inflammatory, analgesic and antipyretic activities were tested in rat paw edema, mouse writhing test and LPS induced rat fever, respectively. Amongst test compounds, 2-methylthio derivatives displayed an ASA-like antiplatelet activity whereas 2-methoxy and, particularly, 2-methanesulfonyl derivatives showed a broad spectrum of antiplatelet action, inhibiting both the ADP- and the AA- and U46619-induced aggregation. With regard to the in vivo pharmacological activities, mainly the 2-methoxy derivatives showed a significant analgesic effect comparable to that of indomethacin. SAR considerations, also in comparison with a number of previously described compounds, were performed.