3-烃基-1(3H)-异苯并硒吩酮的合成及其抗血小板聚集和抗氧化活性
Synthesis and antiplatelet aggregation/antioxidant activity of 3-alkyl-benzo［c］ selenophen-1(3H)-ones
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摘要: 邻苯二甲酰氯( 1 )与硒氢化铝锂反应制备1，3-异苯并硒吩二酮( 2 )，然后与格式试剂加成、水解得3-羟基-3-烃基-1(3H)-异苯并硒吩酮( 3a~3h )，最后在氢碘酸作用下得到目标化合物 4a~4h ，结构经MS及1H NMR确证。采用Born氏比浊法检测目标物对二磷酸腺苷(ADP)诱导的血小板聚集抑制活性；采用黄嘌呤氧化酶法和邻二氮菲法检测目标化合物的抗氧化活性。结果表明，化合物 4a~4h 对 ADP诱导的血小板聚集显示了不同程度的抑制作用，其中化合物 4f 的血小板聚集抑制活性最强，优于丁苯酞。此外，化合物 4f 还显示了较强的体外清除羟基自由基的能力，活性与依达拉奉相当，值得进一步研究。Abstract: Phthaloyl dichloride( 1 )was reacted with LiAlSeH2 to give benzo［c］selenophene-1, 3-dione( 2 ), which was treated with the Grignard reagents to generate hydroxyl compounds 3a-3h . These compounds were finally converted to target products 4a-4h by treatment with hydriodic acid. The structures of 4a-4h were confirmed by MS and 1H NMR. Their inhibitory activity against adenosine diphosphate(ADP)-induced platelet aggregation was evaluated by Born′s turbidimetric assay; free radical scavenging activity was assayed by xanthine oxidasemethod and 1, 10-phenanthroline spectrophotometric method. It was found that compound 4f displayed more potent inhibitory effect on platelet aggregation than 3-n-butylphthalide and comparable hydroxyl free radical scavenging activity in vitro to that of edaravone. Therefore, compound 4f might be the candidate for further investigation.
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