Wang Xin, Gao Feng-Li, Piao Hong-Bin, Cheng Tie-Ming, Li Run-Tao
School of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China.
Bioorg Med Chem Lett. 2003 May 19;13(10):1729-32. doi: 10.1016/s0960-894x(03)00213-0.
Three series of spirocyclopiperazinium derivatives 5a-d, 6a-f and 17a-d were synthesized and evaluated for their in vivo analgesic activities. Compounds 5a, 17a and 17b exhibited excellent analgesic activity. Two important structure-activity relationships were observed from this study: (1) the quaternary ammonium functionality is a critical pharmacophore for analgesic activity; (2) it is important to adjust the lipophilic property of compounds to improve analgesic activity.
合成了三个系列的螺环哌嗪鎓衍生物5a-d、6a-f和17a-d，并对其体内镇痛活性进行了评估。化合物5a、17a和17b表现出优异的镇痛活性。从该研究中观察到两个重要的构效关系：(1) 季铵官能团是镇痛活性的关键药效团；(2) 调节化合物的亲脂性对提高镇痛活性很重要。
