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组胺H_3受体在体内参与调节很多神经递质的释放。人们预期,H_3受体拮抗剂将临床应用于老年性痴呆症、抑郁症、精神分裂症等中枢性疾病。本文使用三维定量构效关系研究方法,包括比较分子场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA),研究芳基苯并呋喃类H_3受体拮抗剂的分子结构与生物活性之间的定量关系。本文使用CoMSIA法所获建三维定量构效关系模型,其交叉验证系数q~2为0.646,非交叉验证相关系数R~2为0.920,表明模型预测能力较好,同时使用“留八法”证实模型的稳定和可靠。模型中各分子场的贡献为:立体场10.4%、静电场56.9%和疏水场32.7%。三维系数等势图和静电势图显示:母核3′和4′位上的取代基对活性影响较大,估计它们是配体与受体作用的位点。本研究结果可为设计和开发活性更高的该类拮抗剂提供理论参考。
Histamine H_3 receptors are involved in regulating the release of many neurotransmitters in the body. It is expected that H_3 receptor antagonists will be clinically applied to central diseases such as Alzheimer’s disease, depression and schizophrenia. In this study, we used three-dimensional quantitative structure-activity relationship research methods, including comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) to study the molecular structure and bioactivity of aryl benzofuran H_3 receptor antagonists The quantitative relationship between. This paper uses the CoMSIA method to build a three-dimensional quantitative structure-activity relationship model, the cross-validation coefficient q ~ 2 is 0.646, non-cross-validation correlation coefficient R ~ 2 is 0.920, indicating that the model prediction ability is better, "Confirms the stability and reliability of the model. The contribution of each molecular field in the model is 10.4% for stereo, 56.9% for electrostatic and 32.7% for hydrophobic. The three-dimensional iso-isostrogram and the electrostatic potential diagram show that the substituents on the 3 ’and 4’ positions of the mother nucleus have a great influence on the activity, and they are estimated to be the site of ligand-receptor interaction. The results of this study provide a theoretical reference for the design and development of more active antagonists.