Synthesis and antidepressant-like activity of novel aralkyl piperazine derivatives targeting SSRI/5-HT1A/5-HT7
Synthesis and antidepressant-like activity of novel aralkyl piperazine derivatives targeting SSRI/5-HT1A/5-HT7
复制标题
靶向SSRI/5-HT1A/5-HT7的新型芳烷基哌嗪衍生物的合成及其抗抑郁样活性
DOI：
10.1016/j.ejmech.2017.12.063
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发表时间：
2018-01-20
影响因子：
6.7
通讯作者：
Li, Jian-Qi
中科院分区：
文献类型：
--
作者：
Gu, Zheng-Song;Zhou, Ai-nan;Li, Jian-Qi
合成了一系列新型芳烷基哌嗪衍生物，并评估了其血清素再摄取抑制和 5-HT1A/5-HT7 受体亲和活性。采用强迫游泳试验(FST)和悬尾试验(TST)筛选化合物的体内抗抑郁活性。结果表明，化合物 21k (RUI, IC50 = 31 nM; 5-HT1A, 5-HT7, k(i); = 62, 12 nM) 和 21n (RUI, IC50 = 25 nM; 5-HT1A, 5-HT7, k(i); = 28, 3.3 nM) 对5-HT1A/5-HT7 受体与有效的血清素再摄取抑制相结合。具体来说，最有前途的化合物 21n 具有良好的口服药代动力学特性和可接受的 hERG 曲线，并在 FST 和 TST 模型中显示出有效的抗抑郁样作用。 (C) 2017 Elsevier Masson SAS。版权所有。
A series of novel aralkyl piperazine derivatives were synthesized, and evaluated for their serotonin re uptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the compounds were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compounds 21k (RUI, IC50 = 31 nM; 5-HT1A, 5-HT7, k(i); = 62, 12 nM) and 21n (RUI, IC50 = 25 nM; 5-HT1A, 5-HT7, k(i); = 28, 3.3 nM) exhibited high affinities for the 5-HT1A/5-HT7 receptors coupled with potent serotonin reuptake inhibition. Specifically, the most promising compound 21n possessed a good oral pharmacokinetic properties and an acceptable hERG profile, and showed potent antidepressant-like effect in the FST and TST models. (C) 2017 Elsevier Masson SAS. All rights reserved.