目的：合成具有抗氧化和GABA增强活性的神经保护试剂并测试其抗脑卒中的神经保护作用。方法：从不同取代的酚出发合成依达拉奉的类似物，用DPPH法测试化合物的抗氧化活性，用膜片钳技术测试化合物的GABA活性，并用大脑中动脉栓塞(middle cerebral artery occlusion, MCAO)模型测试化合物的神经保护作用。结果：合成了3’,5’-二异丙基-4’-羟基依达拉奉(6a)和3’-甲基-5’-叔丁基-4’-羟基依达拉奉(6b)，两个化合物都显示了良好的体外抗氧化活性，在MCAO模型上两个化合物都显示了比依达拉奉更强的神经保护作用；电生理实验表明，化合物6b在低浓度下显示GABA增强活性，在高浓度下显示直接的GABAR激动活性。结论：基于依达拉奉的分子骨架我们成功构建了同时具有抗氧化活性和GABA增强活性的新型神经保护试剂。
Objective: To synthesize multifunctional neuroprotective agent with antioxidant and GABA activity and test their neuroprotective activity against stroke. Methods: The edaravone analogues were synthesized from phenols with distinct substitutes; the antioxidant activity was determined by DPPH free radical scavenging activity; the GABA activity was evaluated by patch clamp, and the neuroprotective effect of the compounds was tested by MCAO model in rats. Results: 3',5'-Diisopropyl-4'-hydroxyedaravone (6a) and 3'-methyl-5'-tert-butyl-4'-hydroxy- edaravone (6b) were successfully synthesized, both compounds showed good in vitro antioxidant activity and stronger neuroprotection than edaravone on the MCAO model; electrophysiological experiments showed that compound 6b shows GABA enhancement activity at low concentration and direct GABAR agonistic activity at high concentration. Conclusion: Based on the molecular framework of edaravone, we have successfully constructed two new neuroprotecting agents with both antioxidant activity and GABA activity.