| 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 |
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| 引用本文： | 汪小涧,张福荣,程桂芳,李春,付继华,尹大力,尤启冬.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[J].中国药科大学学报,2012,43(3):193-198. |
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| 作者姓名： | 汪小涧 张福荣 程桂芳 李春 付继华 尹大力 尤启冬 |
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| 作者单位： | 中国医学科学院北京协和医学院药物研究所，活性物质发现与适药化研究北京市重点实验室;中国医学科学院北京协和医学院药物研究所，药理学研究室;中国医学科学院北京协和医学院药物研究所，药理学研究室;中国医学科学院北京协和医学院药物研究所，活性物质发现与适药化研究北京市重点实验室;中国药科大学药学院;中国医学科学院北京协和医学院药物研究所，活性物质发现与适药化研究北京市重点实验室;中国药科大学药学院 |
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| 基金项目： | 基金项目 国家“重大新药创制”科技重大专项资助项目（No.2009ZX09301-003） |
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| 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。
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| 关 键 词： | 三环类衍生物 H1受体结合活性 豚鼠回肠收缩 分子对接 合成 |
Synthesis,biological evaluation and molecular docking of novel tricyclic desloratadine derivatives |
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| WANG Xiao-jian,ZHANG Fu-rong,CHENG Gui-fang,LI Chun,FU Ji-hu,YIN Da-li and YOU Qi-dong.Synthesis,biological evaluation and molecular docking of novel tricyclic desloratadine derivatives[J].Journal of China Pharmaceutical University,2012,43(3):193-198. |
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| Authors: | WANG Xiao-jian ZHANG Fu-rong CHENG Gui-fang LI Chun FU Ji-hu YIN Da-li and YOU Qi-dong |
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| Institution: | 1Key Laboratory of Active Substance Discovery and Druggability Evaluation,Institute of Materia Medica,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100050;2Department of Pharmacology,Institute of Materia Medica,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100050;3School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China |
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| 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. |
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| Keywords: | tricyclic derivatives H1 receptor binding affinity contraction of guiea-pig ileum molecular docking synthesis |
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