二苯甲基哌嗪类衍生物的合成和抗癫痫作用及作用机制研究

项目名称： 二苯甲基哌嗪类衍生物的合成和抗癫痫作用及作用机制研究

项目编号： No.30860340

项目类型： 地区科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 全哲山

作者单位： 延边大学

项目金额： 28万元

中文摘要： 本课题首先合成设计了二苯哌嗪类衍生物，进行了抗癫痫药理实验。实验结果在此类衍生物中未发现活性强而毒性低的候选化合物。接着，设计合成了十六酰乙醇类衍生物、呋喃香豆素类衍生物、三唑类衍生物，共200多个目标化合物。所合成的化合物的结构以IR、NMR、MS等方法确证。抗癫痫药理实验采用最大电惊厥法，以及戊四唑、硫代氨基脲、3-巯基丙酸等化学物质诱发惊厥法，阐明了这类化合物的构效关系。同时，以旋转棒法测定了神经毒性，寻找到抗癫痫作用强而毒性低的候选药物W112,申请了中国发明专利。本课题共发表SCI收录的论文15篇，申请专利1项，获吉林省科技进步二等奖1项，有3人获得吉林省优秀硕士学位论文。通过完成本课题，有1名获得博士学位，有5名获得硕士学位。

中文关键词： 合成；抗癫痫；抗惊厥；三唑

英文摘要： At the beginning of this research project, we designed and synthesized a series of diphenylpiperazine derivatives, and evaluated their anticonvulsant activities. The pharmacology results showed that those derivatives just exhibited weak anticonvulsant activities, which is to say that the expectation of finding compounds with high activity and low toxicity profiles was not achieved. Sequentially, total more than 200 derivatives of N-(2-hydroxyethyl)palmitamide, furocoumarins, and triazolo were designed and synthesized. All the compounds synthesized were characterized by IR, 1H-NMR, MS and elemental analysis techniques for their structures. Their anticonvulsant activities were evaluated using MES model and chemical substances-induced convulsions model (e.g. Pentylenetetrazole (PTZ), Isoniazid (ISO), thiosemicarbazide (TSC), 3-Mercaptopropionic acid (3-MP), and Bicuculline (BIC). Their neurotoxicity was evaluated with the rotarod test. From their activities evaluation results, the structure-activity relationships (SARs) were obtained, and some promising compounds were obtained with strong effect and low toxicity profiles. Among them, the best one W112 was chosen to the further study for drug-generating. And the China patent of invention of it has been applied. Based on this research project, we published 15 SCI articles, applied 1 patent, obtained Jilin Province Science and Technology Progress Award Proxime Accessit, and 3 excellent theses for master's degree of Jilin. 1 Ph.D candidate and 5 master students have graduated smoothly via finishing this project.

英文关键词： Synthesis;anticonvulsant;antiepileptic； triazole