5-取代-1,2,4-三唑并[4,3-a]喹唑啉衍生物的合成及抗惊厥活性有机化学.pdfVIP

2011 年第 31 卷 有 机 化 学 Vol. 31, 2011 第 12 期, 2082～2087 Chinese Journal of Organic Chemistry No. 12, 2082～2087 ·研究论文· 5-取代-1,2,4-三唑并[4,3-a]喹唑啉衍生物的合成及抗惊厥活性 * 邓先清 肖春瑞 魏成喜 全哲山 (延边大学药学院 延吉 133002) 摘要 合成了 5-取代-1,2,4-三唑并[4,3-a]喹唑啉衍生物 2a～2q. 利用最大电惊厥 (MES)和旋转棒 (Rotarod Test), 以 小鼠腹腔给药, 分别测定了其抗惊厥活性和神经毒性. 药理实验结果表明, 化合物 5-正庚氧基-1,2,4-三唑并[4,3-a]喹唑 啉(2d) 的抗惊厥活性最强, 其半数有效量 ED50 为 19.7 mg/kg, 保护指数 PI 为 6.2. 由化学物质诱发的抗惊厥实验结果表 明, 化合物 2d 能对抗由戊四唑、异烟肼、硫代氨基脲和 3-巯基丙酸诱发的惊厥作用, 推测其抗惊厥作用是通过增强 γ-aminobutyric acid (GABA)神经能系统和活化谷氨酸脱羧酶或抑制 GABA 转氨酶而起抗惊厥作用. 关键词 三唑并喹唑啉; 合成; 抗惊厥; 戊四唑; 旋转棒 Synthesis and Anticonvulsant Activity of 5-Substituted- [1,2,4]triazolo[4,3-a]quinazolines Deng, Xianqing Xiao, Chunrui Wei, Chengxi Quan, Zheshan* (College of Pharmacy, Yanbian University, Yanji 133002) Abstract A series of 5-substituted-[1,2,4]triazolo[4,3-a]quinazolines were synthesized. The anticonvulsant effects and neurotoxicity of the compounds were evaluated with maximal electroshock test and rotarod test with intraperitoneally injected in mice. The pharmacology results showed that 5-pentyloxy-[1,2,4]triazolo- [4,3-a]quinazoline (2d) was the most potent with ED50 value of 19.7 mg/kg and protective index (PI ＝ TD50/ED50) value of 6.2. To explain the possible mechanism of anticonvulsant activity, compound 2d was tested in several chemical induced seizures tests. The results revealed that comp