异吲哚啉衍生物作为5-羟色胺/去甲肾上腺素双重再摄取抑制剂的设计、合成及药理研究

[Design, synthesis and pharmacological investigation of isoindoline derivatives as 5-HT/NE double reuptake inhibitors].

作者信息

Wen Hui, Shi Yuan, Dong Jing-wen, Guo Yan-shen, Zang Jian-Jun, Yang Guang-zhong

出版信息

Yao Xue Xue Bao. 2015 Sep;50(9):1148-55.

Abstract

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.

摘要

设计、合成了一系列异吲哚啉衍生物，并对其双重抑制活性进行了评估。它们均为新化合物，其结构通过1H NMR和HR-MS得以确证。初步体外药理试验表明，所有化合物均表现出5-羟色胺（5-HT）或去甲肾上腺素（NE）再摄取抑制活性。在所测试的化合物中，化合物I-3在体外对5-HT和NE再摄取表现出强效抑制活性，在体内表现出强效抗抑郁活性。所设计的这些化合物可进一步优化，以寻找更有效的5-HT/NE双重再摄取抑制剂以及抗抑郁候选药物。

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