Design, synthesis and evaluation of 1,4-benzodioxine derivatives as novel platelet aggregation inhibitors

Aim: To find novel platelet aggregation inhibitors, two new series of 1,4-benzodioxine derivatives were synthesized and screened for the ability to inhibit platelet aggregation. Materials & methods: The synthesized compounds were evaluated for antiplatelet aggregation activity using human blood platelet and GPIIb/IIIa antagonistic activity. Results: Compound 9-2p showed significant antiplatelet activity with the IC50 values of 41.7 and 22.2 mu M induced by ADP and thrombin, respectively, more potent than that of LX2421. Compound 9-2p exhibited GPIIb/IIIa antagonistic activity with the IC50 value of 2.3 mu M, as potent as RGDs. In vivo study showed that 9-2p displayed remarkable antithrombotic activity, more effective than LX2421, but less effective than tirofiban. Conclusion: Compound 9-2p showed moderate antiplatelet activity and antithrombotic activity, which could be further optimized based on the target of GPIIb/IIIa.