Synthesis and Pharmacological Evaluation of 4 H ‐Chromene‐3‐Carbonitrile Derivatives as Antiplatelet Agents

A series of 4H-Chromene-3-carbonitrile derivatives was synthesized, and their in vitro antiplatelet activities were evaluated against arachidonic acid (AA) and adenosine diphosphate (ADP) in plasma. Among the synthesized compounds, 4H-Chromene-3-carbonitrile derivative with a 4-methoxy group (4j) exhibited the most potent antiplatelet activity against AA-induced aggregation. Almost no activity was observed against the aggregation induced by ADP. Additionally, the in vivo antiplatelet activity of the most potent compound was evaluated using bleeding time and aggregation tests in rats. Compound 4j showed antiplatelet activities in both the oral and intravenous routes of administration in bleeding time and aggregation tests. Notably, the effects were comparable with indomethacin. The structure-activity relationship (SAR) study suggested that the antiplatelet activity of the compound might be governed by the electronic properties of the substituent on the ring of the derivative. The electron-donating groups at the 4' position resulted in the most active derivative. Our results show that compound 4j may be an appropriate compound for future investigations in the field of antiplatelet drug discovery.