论文部分内容阅读
为寻找镇痛活性更好的化合物,以前期发现的螺环哌嗪季铵盐类化合物1为先导物,设计合成了8个未见文献报道的衍生物.通过~1H NMR,~(13)C NMR和元素分析或高分辨质谱确定了化合物的结构.利用小鼠醋酸扭体模型初步评价了它们的镇痛活性,构效关系研究表明,苯环上的羟基是关键的药效团,与开链季铵盐相比,螺环季铵盐结构对活性更有利;扩大螺环和引入取代基对活性不利.
In order to search for compounds with better analgesic activity, eight previously reported derivatives of spiropiperazines quaternary ammonium salts were designed and synthesized.H NMR, ~ (13) C NMR and elemental analysis or high-resolution mass spectrometry were used to determine the structure of the compounds. The analgesic activity of the compounds was evaluated primarily by the mouse model of acetic acid writhing. The structure-activity relationship study shows that the hydroxyl groups on the phenyl ring are the key pharmacophores, The spirocyclic quaternary ammonium salt structure is more active than the open-chain quaternary ammonium salt; expanding the spirocyclic ring and introducing substituents are detrimental to activity.