物理化学学报 >> 1995, Vol. 11 >> Issue (05): 419-423.doi: 10.3866/PKU.WHXB19950507

研究论文 上一篇    下一篇

雪花胺类化合物的三维构效关系研究

骆兆文, 王丹丹, 来鲁华, 徐筱杰, 李崇熙   

  1. 北京大学化学系|北京 100871
  • 收稿日期:1994-07-19 修回日期:1994-10-20 发布日期:1995-05-15
  • 通讯作者: 来鲁华

3D-QSAR Studies of Galanthamine and Analogs

Luo Zhao-Wen, Wang Dan-Dan, Lai Lu-Hua, Xu Xiao-Jia, Li Chong-Xi   

  1. Department of Chemistry,Peking University,Beijing 100871
  • Received:1994-07-19 Revised:1994-10-20 Published:1995-05-15
  • Contact: Lai Lu-Hua

PDF

2563

赞

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荷性质．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．

关键词: 雪花胺, 三维定量构效关系, 乙酰胆碱酯酶, 抑制剂

Abstract:

Galanthamine is an inhibitor of acetylcholinesterase and a potent drug to treat Alzheimer’s disease. According to the known pharmacological characterization of galanthamine and it s analogs, we conducted 3D-QSAR studies on this kind of compounds. The lowest energy conformations of compounds were obtained from molecular mechanics calculations. Then these conformations were used in the CoMFA analysis and 3D-QSAR was constructed. The dominant factor which affect activity was steric effect, whereas electrostatic effect only played an unimportant role. On the analysis of steric effect, we found that replacement of large group was disadvantage for the activity. The electrostatic features in different position were also acquired.

Key words: Galanthamine, 3D-QSAR, Acetylcholinesterase, Inhibitor