新型三环类地氯雷他定衍生物的合成、生物活性与分子对接

Synthesis,biological evaluation and molecular docking of novel tricyclic desloratadine derivatives

摘要: 以三环类抗组胺药物地氯雷他定为母体，设计并合成了一系列取代的三环类衍生物。所有目标化合物均通过核磁共振氢谱和高分辨质谱表征确定。H₁受体结合活性测试结果表明：化合物 7 拮抗组胺H₁受体的活性显著优于先导化合物地氯雷他定。组胺诱导的豚鼠回肠收缩实验显示化合物 7 可显著抑制回肠收缩。构效关系研究表明：化合物的疏水参数lgP的计算值与拮抗H1受体的活性具有相关性。并进一步利用分子对接技术研究了化合物 7 与H₁受体的结合模式。

Abstract: A new series of tricyclic derivatives were designed and synthesized on the basis of the structure of desloratadine.All the target compounds were identified by ¹H NMR and HR-MS.The H₁ receptor binding affinity experiment indicated that compound 7 was significantly more active than desloratadine.The in vitro histamine induced the contraction of guiea-pig ileum.Results showed that compound 7 had strong inhibitory activity on the ileum contraction.SAR study indicated that the calculated lgP values of compounds were consistent with their antihistamine activity.The binding mode of compound 7 and homology mode of H₁ receptor have been predicted by further molecular docking.