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有机化学 ›› 2007, Vol. 27 ›› Issue (12): 1567-1572. 上一篇    下一篇

研究简报

7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉和喹啉-1(2H)-酮衍生物的合成及抗惊厥活性

金云哲a,b，关丽萍b，赵立明b，朴虎日b，全哲山*,a,b   

  1. (a延边大学长白山生物功能因子省部共建教育部重点实验室 延吉 133002)
    (b延边大学药学院 延吉 133000)
  • 收稿日期:2007-03-25 修回日期:2007-05-10 发布日期:2007-12-04
  • 通讯作者: 全哲山

Synthesis and Anticonvulsant Activity Study of 7-SubstitutedPhenoxyl-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolines andQuinoline-1(2H)-ones

JIN Yun-Zhea,b, GUAN Li-Pingb, ZHAO Li-Mingb, PIAO Hu-Rib
QUAN Zhe-Shan*,a,b   

  1. (a Key Laboratory of Organism Functional Factors of the Changbai Mountain, Ministry of Education,
    Yanbian University, Yanji 133002)
    (b College of Pharmacy, Yanbian University, Yanji 133000)
  • Received:2007-03-25 Revised:2007-05-10 Published:2007-12-04
  • Contact: QUAN Zhe-Shan

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合成了7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉(3a～3g)和7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹表明啉-1(2H)-酮(4a～4g)类衍生物. 以最大电惊厥法和戊四唑法测定了抗惊厥活性, 以旋转棒法测定了神经毒性. 结果表明, 化合物7-(4-氟苯氧基)-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉-1(2H)-酮(4c)显示最强的抗惊厥作用和低的神经毒性, 其抗电惊厥ED50为6.8 mg/kg, 神经毒性TD50为88.0 mg/kg, 保护指数PI为12.9, 明显优于对照药苯妥英钠.

关键词: 三唑, 喹啉, 1,2,4-三唑并[4,3-a]喹啉, 抗惊厥, 合成

A series of 7-(substituted phenoxyl)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines and 7-(substi- tuted phenoxyl)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-ones were synthesized. The convulsant effect and neurotoxicity of the compound were determined with maximal electroshock test (MES), pentylenetetrazol (PTZ) method and rotarod test intraperitoneally in mice. 7-(4-Fluorophenyloxy)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-one (4c) was the most active and also has the lowest toxicity. In the anti-MES potency test, 4c showed a medial effective dose (ED50) of 6.8 mg/kg, a medial toxicity dose (TD50) of 88.0 mg/kg, and the protective index (PI) of 12.9. The PI value of compound 4c was better than that of the marketed drug phenytoin.

Key words: quinoline, [1,2,4]triazolo[4,3-a]quinoline, anticonvulsant, synthesis, triazole