度洛西汀衍生物的设计、合成及抗抑郁活性

Design, synthesis and antidepressive activity of duloxetine derivatives

摘要:
本文以3-芳氧基-3-芳基丙胺类抗抑郁药物为研究背景, 以度洛西汀为先导化合物, 引入5-HT_1A受体拮抗药效团代替原分子中萘环, 设计合成了新型度洛西汀衍生物, 以期达到安全有效、快速起效的抗抑郁目的。通过元素分析、¹H NMR、MS 对化合物结构进行了表征, 并进行了初步的药效评价研究。结果表明这些化合物大部分显示不同程度的抗抑郁活性, 部分化合物抗抑郁有效剂量显著低于度洛西汀, 同等剂量下抗抑郁作用显著强于度洛西汀, 具有良好的剂量依赖性, 值得进一步研究。

Abstract:
In this paper, duloxetine was chosen as the lead compound. The pharmacophores with 5-HT_1A antagonism activity were used to replace the naphthyl of duloxetine. A series of duloxetine derivatives had been designed and synthesized and whose structures were confirmed with elemental analysis, MS and ¹H NMR. All synthesized compounds were tested by tail suspension test and forced swimming test in vivo. The test results revealed that most of the compounds have shown better activity than duloxetine at the same dosage. Some of them are worth to be studied further.