高级检索

    吗氯贝胺衍生物的设计、分子对接、合成及抗抑郁活性

    Design, Molecular Docking, Synthesis and Antidepressant Activity of Moclobemide Derivatives

      摘要
    • 摘要:
      目的  合成了6个新型吗氯贝胺衍生物，并进行了药理活性研究。
      方法 以吗氯贝胺为先导化合物，运用分子对接技术设计并筛选出具有良好结合活性的衍生物。以溴代芳基丙酮、氨基丙醇与芳基甲酰氯为原料，通过胺化反应、Leuckart-wallach还原反应、酸化反应和酰化反应，合成了6个新结构化合物，采用小鼠强迫游泳试验对目标化合物进行抗抑郁药理活性实验研究。
      结果 目标化合物结构经1H-NMR、13C-NMR、IR及MS确证，化合物5a、5b小鼠强迫游泳不动时间分别为(56.8±15.2)s及(47.2±13.1)s，显著低于空白对照组(154.6±37.2)s(P<0.05)，与吗氯贝胺小鼠强迫游泳不动时间(45.7±12.7)s相当。
      结论 该合成路线反应条件温和且易于操作，目标化合物5a、5b显示出较好的抗抑郁活性。

       

      Abstract:
      OBJECTIVE To synthesis 6 novel morpholino derivatives and study their pharmacological activity.
      METHODS Based on moclobemide as the lead compound, the derivatives with good binding activity were designed and screened using molecular docking technique. Six novel compounds were synthesized by amination, Leuckart-wallach reduction, acidification and acylation reactions using brominated aryl acetone, aminopropanol and aryl carbonyl chloride as raw materials, and the target compounds were investigated for antidepressant activity using forced swimming assay in mice.
      RESULTS The target compounds were structurally verified by 1H-NMR, 13C-NMR, IR and MS, and the forced swimming immobility time in mice for compounds 5a and 5b was (56.8±15.2)s and (47.2±13.1)s, respectively, which was significantly lower than that of the blank control (154.6±37.2)s(P<0.05), and was comparable to the forced swimming immobility time in mice for morpholino (45.7±12.7)s comparable.
      CONCLUSION The synthetic route has mild and easy reaction conditions, and the target compounds 5a and 5b show good antidepressant activity.

       

      • HTML全文
      • 参考文献(12)
      • 相关文章
      • 施引文献
    • 资源附件(0)

    /

    返回文章
    返回