基于Topomer CoMFA方法的苯并呋喃类褪黑激素受体拮抗药的三维定量构效关系研究  

Three-dimensional Quantitative Structure Activity Relationship Study of Benzofuran Melatonin Receptor Antagonists Based on Topomer CoMFA Method

作　　者：方明阳 梁佳龙 孙智勇[1] 王菲 Fang Mingyang;Liang Jialong;Sun Zhiyong;Wang Fei(No.946 Hospital of People’s Liberation Army Ground Force,Xinjiang Yili 835000,China;School of Pharmacy,Air Force Medical University;Shaanxi Institute for Food and Drug Control)

机构地区：[1]中国人民解放军陆军第946医院,新疆伊宁835000 [2]空军军医大学药学院 [3]陕西省食品药品监督检验研究院

出　　处：《中国药师》2020年第10期1910-1914,共5页China Pharmacist

基　　金：军队后勤科研计划项目面上项目(编号:CLJ20J027)。

摘　　要：目的:建立苯丙呋喃类化合物褪黑激素受体拮抗药的三维定量构效关系(3D-QSAR)模型。方法:使用SYBYLx2.1.1软件中的Topomer CoMFA模块对29个苯并呋喃类分子进行三维定量构效关系分析。保留母核结构切割后得到了3个R基片段,分别计算所产生的立体场与静电场。结果:对于褪黑激素受体1(MT1)和褪黑激素受体2(MT2)分别建立了可靠、合理的Topomer CoMFA模型(MT1:q2=0.650,r2=0.924;MT2:q2=0.486,r2=0.920)。结论:建立的Topomer CoMFA模型阐明了苯并呋喃类化合物分子对褪黑激素受体的生物活性的影响因素。通过分析实验化合物MT1与MT2的活性值比值(MT1/MT2),发现R2基团的电负性变化可能使该类化合物对两种受体表现出不同选择性。Objective:To establish the three-dimensional quantitative structure-activity relationship(3D-QSAR)model of phenylpropanfuran compounds melatonin receptor antagonists.Methods:The Topomer CoMFA module in the SYBYL-x2.1.1 software was used to analyze the 3D-QSAR of 29 benzofuran molecules.After cutting the core structure,three R-based fragments were obtained,and the generated three-dimensional field and electrostatic field were calculated respectively.Results:Reliable and reasonable Topomer CoMFA models were established for melatonin receptor 1(MT1)and melatonin receptor 2(MT2)(MT1:q2=0.650,r2=0.924;MT2:q2=0.486,r2=0.920).Conclusion:The established Topomer CoMFA model clarified the influencing factors of benzofuran molecules in the biological activity of melatonin receptors.By analyzing the ratio of activity values of the experimental compounds MT1 and MT2(MT1/MT2),it was found that the electronegativity change of the R2 group may make the compounds exhibit different selectivity for the two receptors.

关 键 词：褪黑激素受体 三维定量构效关系 Topomer CoMFA 

分 类 号：R914.2[医药卫生—药物化学]