Synthesis of Gingerdione Derivatives as Potent Antiplatelet Agents

In search of novel antiplatelet agents, the naturally-occurring gingerdiones (20, 24) were selected as lead com pounds. A series of their derivatives were synthesized and screened for anti-platelet activity. It was found that all of the synthesized gingerdione derivatives demonstrated potent inhibition against AA-induced platelet aggregation. Among them, 141-gingerdione (I8) and 51-gingerdione (19) showed the highest potency, being about 1/3 and one time as potent as indomethacin, respectively. Preliminary studies indicated that the mechanism of action of these gingerdione derivatives differed from indomethacin. Unlike indomethacin, they showed no appreciable COX-I and COX-2 inhibition. The exact mechanism of action of these new compounds