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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.
Glutamine is an important class of acetylcholinesterase inhibitors that may develop into drugs for the treatment of Alzheimer’s disease.The dominant conformations of these compounds were calculated by molecular mechanics and the CoMFA studies of these compounds were performed. It is found that for galanthamine compounds, the main factor that affects the drug efficacy is the spatial structure, with less influence of charge forces. Further analysis of the spatial factors found that, for such molecules, should not be replaced by a larger empty space group. The charge-dependent analysis gives the nature of the electrical properties of the substituents at different positions. The quantitative three-dimensional structure-activity relationship studies provide a protocol for the design of inhibitors based on galanthamine.