新型5-HT重摄取抑制剂的设计、合成及活性评价  

Design,Synthesis and Activity Evaluation of Novel Selective Serotonin Reuptake Inhibitors

作　　者：杨静[1] 王小芳[1] 杜冠华[1] 秦芳[1] 文辉[1] 杨光中[1] 

机构地区：[1]中国协和医科大学中国医学科学院药物研究所,北京100050

出　　处：《高等学校化学学报》2007年第8期1503-1507,共5页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:30572233);北京市自然科学基金(批准号:7062045)资助

摘　　要：在对已知各种结构类型的5-HT重摄取抑制剂分子结构全面分析的基础上,建立了SSRIs药效团模型.基于该模型应用UNITY程序对NCI-3D和Maybridge-3D数据库进行三维结构的限制性查询,在获得的命中结构的信息指导下,设计合成了3种全新结构类型的化合物,并完成了初步的药理活性评价.这些化合物均显示出不同程度的5-HT重摄取抑制活性,其中5个化合物显示高抑制活性.哌嗪取代的二苯脒类化合物的结构新颖,较好地符合5-HT重摄取抑制剂药效团模型,与SSRIs类化合物三维定量构效关系研究得到的CoMFA模型有较好的适配性.Depression is a kind of common and severe mental illness. During the past two decades, selective serotonin reuptake inhibitors （SSRIs） have been proved to be a safer and more effective resistance than the first-generation antidepressants（ TCAs and MAOIs）, and have gained incredible popularity. Based on the conformation analysis and pharmacophore information of SSRIs, flexible database searching from the NCI-3D and Maybridge-3 D database was performed. Three classes of the new compounds structures were designed and 27 analogues were prepared and evaluated as potential antidepressant agents. Biphenylbenzamidine derivative 1-19 showed good activity of affinity to the 5-HT transporter. It can be used as the lead structure for drug design with the objective of making more potent inhibitors against 5-HT transporter.

关 键 词：选择性5-HT重摄取抑制剂(SSRIs) 抗抑郁 药效团 

分 类 号：O626[理学—有机化学]