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本文基于已有的先导结构,结合前期已建立的药效团模型,利用骨架迁越的策略设计并合成两类全新结构类型的异吲哚啉类化合物,通过1H NMR、HR-MS对化合物结构进行了确证,完成了初步的药理活性评价。结果显示,这些化合物均有不同程度的5-HT再摄取抑制活性和NE再摄取抑制活性,其中化合物I-3显示出较强的5-HT再摄取抑制活性和NE再摄取抑制活性,并且在整体动物抗抑郁药效学实验中表现出明确的抗抑郁效果,以及较低的毒副作用,值得进一步研究。
In this paper, based on the existing pilot structure, two new types of isoindoline compounds were designed and synthesized by using the strategy of skeletal relocation based on the previously established pharmacophore model. The structures of the compounds were characterized by 1H NMR and HR-MS. Confirmed, completed the initial assessment of pharmacological activity. The results showed that these compounds all have varying degrees of 5-HT reuptake inhibitory activity and NE reuptake inhibitory activity, among which Compound 1-3 shows strong 5-HT reuptake inhibitory activity and NE reuptake inhibitory activity, The overall antidepressant pharmacodynamic experiments in animals show a clear antidepressant effect, as well as lower toxicity, it is worth further study.