摘要
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。
A series of isoindoline derivatives were designed, synthesized, and evaluated for their double inhibitory activities. All of them were new compounds, and their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological tests showed that all compounds exhibited 5-HT or NE reuptake inhibition activity. Among the tested compounds, compound I-3 exhibited potent inhibitory activity against 5-HT and NE reuptake in vitro, and exhibited potent antidepressant activity in vivo. These compounds designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.
出处
《药学学报》
CAS
CSCD
北大核心
2015年第9期1148-1155,共8页
Acta Pharmaceutica Sinica
基金
北京市自然科学基金资助项目(7102116)
