莨菪烷衍生物的合成及其活性研究  

Synthesis and Biological Activity of Tropane Derivatives

作　　者：刘慧中[1] 崔永耀[1] 钮因尧[1] 冯菊妹[1] 陈红专[1] 陆阳[1] 

机构地区：[1]上海交通大学医学院药学系,上海200025

出　　处：《中国药学杂志》2007年第14期1112-1115,共4页Chinese Pharmaceutical Journal

基　　金：上海市科委基金资助项目(034319230)

摘　　要：目的设计、合成并筛选具有胆碱能活性,且对M1受体有选择性的莨菪烷衍生物。方法以3α-羟基-6β-乙酰氧基莨菪烷为原料,通过酰化反应制备3α-烃氧基乙酰氧基-6β-乙酰氧基莨菪烷类衍生物,通过核磁共振及质谱鉴定所合成的化合物。运用豚鼠离体回肠纵肌M受体动力学实验方法以及人源M1,M2受体亚型基因转染的CHO细胞系放射配基受体结合法,对合成的化合物进行活性筛选。结果制备了6个新的3α-烃氧基乙酰氧基-6β-乙酰氧基莨菪烷a^f。化合物d,e对M受体有良好的亲和力及内在活性,并对M1受体具有亚型选择性。结论化合物d,e为具有M1受体亚型选择性的胆碱能活性化合物。OBJECTIVE To synthesize and screen tropane derivatives with cholinergic activity and subtype-selectivity of M1 receptor. METHODS Six novel 3α-alkoxyacetoxy-6β-acetoxy tropanes were prepared from 3α-hydroxy-6β-acetoxy tropane by acylating reaction. The structures of the compounds were identified by ^1H-NMR and MS Spectra. Biological activity of prepared compounds was evaluated by dynamic test on M-receptor of guinea pig longitudinal ileul muscles and radioligand binding assay on human M1, M2 gene transfected CHO cell lines. RESULTS Six novel compound a - f were prepared and compound d and e exerted high affinity and intrinsic actitity on muscarinic receptors and also had relative M1 receptor selectivity. CONCLUSION Compound d and e appear to possess cholinergic activity and subtype-selectivity of M1 receptor.

关 键 词：莨菪烷 M1受体选择性 胆碱能活性 

分 类 号：R916[医药卫生—药学]