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有机化学
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有机化学 ›› 2011, Vol. 31 ›› Issue (12): 2082-2087. 上一篇    下一篇

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*   

  1. (延边大学药学院 延吉 133002)
  • 收稿日期:2011-03-14 修回日期:2011-06-22 发布日期:2011-08-15
  • 通讯作者: 全哲山 E-mail:quanzheshan@yahoo.com.cn

Synthesis and Anticonvulsant Activity of 5-Substituted- [1,2,4]triazolo[4,3-a]quinazolines

DENG Xian-Qing, XIAO Chun-Rui, WEI Cheng-Xi, QUAN Zhe-Shan   

  1. (College of Pharmacy, Yanbian University, Yanji 133002)
  • Received:2011-03-14 Revised:2011-06-22 Published:2011-08-15
  • Contact: quan zheshan E-mail:quanzheshan@yahoo.com.cn

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合成了5-取代-1,2,4-三唑并[4,3-a]喹唑啉衍生物2a～2q. 利用最大电惊厥法(MES)和旋转棒法(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, 旋转棒法

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 compound 2d was effective against the seizures induced by pentylenetetrazole, isoniazid, 3-mercaptopropionic acid and thiosemicarbazide, which suggested that the anticonvulsant effects of this series compounds were acted via increasing γ-aminobutyric acid (GABA) ergic neurotransmission and activating glutamate decarboxylase (GAD) or inhibiting α-oxoglutarate aminotransferase (GABA-T) in the brain.

Key words: triazoloquinazoline, synthesis, anticonvulsant, pentylenetetrazole, rotarod test