雪花胺类化合物的三维构效关系研究  

3D-QSAR Studies of Galanthamine and Analogs

作　　者：骆兆文 王丹丹 来鲁华[1] 徐筱杰[1] 李崇熙[1] 

机构地区：[1]北京大学化学系,北京100871

出　　处：《物理化学学报》1995年第5期419-423,共5页Acta Physico-Chimica Sinica

基　　金：‘863’高技术计划!863-103-22-2

摘　　要：雪花胺是一类重要的乙酰胆碱脂酶抑制剂，有可能发展成治疗阿尔茨海默病的药物.利用分子力学计算得到了这类化合物的优势构象，并对这些化合物进行了CoMFA研究．发现，对于雪花胺类化合物，影响其药效的主要因素是空间结构，电荷作用力的影响较小．对空间因素的进一步分析发现，对于该类分子，不宜用空阻较大的基团进行取代．由电荷影响的分析得到了在不同位置上取代基所应有的电行性质．三维定量构效关系研究为基于雪花胺的抑制剂设计提供了方案．Galanthamine is an inhibitor of acetylcholinesterase and a potent drug to treatAlzheimer's disease. According to the known pharmacological characterization of galan thamine and it's analogs, we conducted 3D-QSAR studies on this kind of compounds.The lowest energy conformations of compounds were obtained from molecular mechedcscalculations. Then these conformions were used in the CoMFA analysis and 3D-QSARwas constructed. The dondnant factor which thect activity was steric effect, whereaselectrostatic effect only played an twortam role. On the analysis of steric effect, wefound that replacement of large group was disadvatage for the activity. The electrostaticfeatures in different position were also acquired.

关 键 词：雪花胺 三维定量构效分析 乙酰胆碱脂酶 抑制剂 

分 类 号：R962[医药卫生—药理学]