3α-磺酰氧(氨)取代的莨菪烷衍生物的合成及其生物活性  

Synthesis and Bioactivities of 3α-Sulfonyloxy and Sulfonylamido Tropane Derivatives

作　　者：杨丽敏[1] 钮因尧[1] 谢一凡[1] 冯菊妹[2] 陈红专[2] 陆阳[1] 

机构地区：[1]上海第二医科大学基础医学院化学教研室,上海200025 [2]上海第二医科大学基础医学院药理教研室,上海200025

出　　处：《上海第二医科大学学报》2005年第3期220-222,234,共4页Acta Universitatis Medicinalis Secondae Shanghai

基　　金：上海市科委重点医药研究基金(034319230)上海市教委学科建设专项基金(JY2001)资助项目.

摘　　要：目的设计和合成3α-磺酰氧和磺酰氨取代的莨菪烷衍生物,考察其拟胆碱活性。方法以3α-羟基莨菪烷、6β-乙酰氧基-3α-羟基莨菪烷或6β-乙酰氧基-3α-氨基莨菪烷为起始物,利用磺酰化反应合成莨菪烷衍生物。结果合成了10个新化合物。兔瞳孔实验和离体豚鼠回肠实验表明:4个6β-乙酰氧基-3α-磺酰氧基莨菪烷具有拟胆碱活性,而3α-磺酰氧基莨菪烷和6β-乙酰氧基-3α-磺酰氨基莨菪烷无拟胆碱活性。结论　6β-乙酰氧基是拟胆碱莨菪烷衍生物的活性必需结构,3α-取代基对此类化合物的拟胆碱活性影响很大。Objective To design and synthesize 3α-sulfonyloxy and sulfonylamido tropane derivatives and investigate their cholinergic activities. Methods The title compounds were synthesized from 3α-hydroxytropane, 6β-ace-toxy-3α-hydroxytropane or 6β-acetoxy-3α-aminotropane by sulfonylation. Results Ten new compounds were prepared. Four 6β-acetoxy-3α sulfonyloxytropanes showed cholinergic activities in myotic experiments in rabbits and contraction tests of ileal muscles of guinea pig, but 3 α-sulfonyloxytropanes and 6β-acetoxy-3α-sulfonylamidotropanes showed no cholinergic activities. Conclusion 6β-Acetoxyl in the title compounds is the key group for their cholinergic activities, and the activities can be critically affected by 3α-substituted groups.

关 键 词：新化合物 回肠 离体 胆碱 瞳孔 衍生物 豚鼠 取代 合成 磺酰化 

分 类 号：R914.5[医药卫生—药物化学]