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

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H1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。

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.