山莨菪碱的结构修饰与构效关系

 目的观察山莨菪碱衍生物的抗胆碱活性,总结其构效关系。方法通过将山莨菪碱的羟基选择性地乙酰化,氮原子甲基化,制备山莨菪碱衍生物;利用波谱方法鉴定其结构;通过兔瞳孔实验和离体豚鼠回肠肌实验观察制备化合物的胆碱能活性。结果制备了5个山莨菪碱衍生物(1～5),其中1,3,4和5是新化合物;兔瞳孔实验和离体豚鼠回肠肌实验显示1和5有明显的抗胆碱活性。结论山莨菪碱及其衍生物的6β-羟基乙酰化,将导致其抗胆碱活性减弱或消失;氮原子季铵化,将使其抗胆碱活性增强。

Structure Modification and Structure-Activity Relationship of Anisodamine

OBJECTIVE To observe the anticholinergic activity of the derivatives of anisodamine and summarize the structure-activity relationship.METHODS The hydroxyl groups were selectively acetylated and N atom was methylated respectively to prepare the derivatives of anisodamine.The structures were determined by IR,1H-NMR,MS.Using pupils of rabbits and ileal muscles of guinea pig,the anticholinergic activity of the compounds was tested.RESULTS Five derivatives of anisodamine were prepared and compound 1,3,4 and 5 were new compounds.Compound 1 and 5 showed anticholinergic activity in mydriatic experiments of rabbits and tests of ileal muscles of guinea pig.CONCLUSION Anticholinergic activity may be weakened after acetylating of 6β-hydroxyl of anisodamine and strengthened after its tertiary amine was changed into quaternary.