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目的：寻找活性强，毒性低的新型镇痛药物。方法：以１甲基哌嗪为起始原料， 通过与不同的二酰氯反应得双二酰基哌嗪（ Ｉ Ｉ Ｉａｄ） ， Ｉ Ｉ Ｉａｄ 分别用不同的溴化物季铵化得６ 个新的１ ，１二酰基４ ，４ ，４′，４′四烷基双哌嗪双季铵盐溴化物（ Ｉ Ｖａｆ） 。结果：初步生物活性试验结果表明，这些化合物均有一定的镇痛和镇静活性， 尤其是 Ｉ Ｖｅ（ 剂量２０ ｍ ｇ·ｋｇ － １ ， 镇痛活性８０３ ％ ，镇静活性９５３ ％ ） 和 Ｉ Ｖｆ（ 剂量０５ ｍｇ·ｋｇ － １ ， 镇痛活性７５５ ％ ，镇静活性５３８ ％ ） 活性显著。结论：构效关系研究表明，两个季氮原子之间的距离对活性和毒性有较大影响，当ｎ ＝ ４ 时， 活性最强，而毒性随两个季氮原子之间距离的减小而降低。苄基的引入可使活性明显增强，而且毒性降低。
Objective: To find a new active analgesic drug with low toxicity. Methods: 1 methylpiperazine as the starting material, through the reaction with different diacid dichloride di (IIa d), I Ia d were quaternized with different bromide 6 new 1, 1 diacyl 4, 4, 4 ’, 4’ tetraalkyl dipiperazine bis quaternary ammonium bromide (I Va f). Results: The preliminary bioassay results showed that these compounds had certain analgesic and sedative activity, especially I Ve (20 m g · kg -1, analgesic activity 803%, sedation activity 953%), And I Vf (0.5 mg · kg -1, 75.5% analgesic activity and 53.8% sedation activity). Conclusion: The study of structure-activity relationship shows that the distance between two quaternary nitrogen atoms has a great influence on the activity and toxicity. When n = 4, the activity is the strongest, while the toxicity decreases with the distance between two quaternary nitrogen atoms Lower. The introduction of benzyl can be significantly enhanced activity, but also reduced toxicity.