I_(2)-IR配体双环α-亚氨基膦酸酯定量构效关系研究  

Quantitative Structure-activity Relationship of Bicyclicα-iminophosphonates with Imidazoline I_(2)Receptor Ligands

作　　者：时美淇 侯景轩 谷庆山 高辉 郑璐 吴庆昆 SHI Meiqi;HOU Jingxuan;GU Qingshan;GAO Hui;ZHENG Lu;WU Qingkun(School of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,China)

机构地区：[1]江苏海洋大学药学院,江苏连云港222005

出　　处：《江苏海洋大学学报（自然科学版）》2023年第3期56-62,共7页Journal of Jiangsu Ocean University:Natural Science Edition

基　　金：江苏省海洋资源开发研究院开放课题(JSIMR202015);江苏海洋大学博士科研项目(KQ20029,KQ20065)。

摘　　要：咪唑啉I 2受体(I_(2)-IR)对阿尔茨海默症(AD)和其他神经退行性疾病的治疗具有重要意义。为获得更高活性的I_(2)-IR配体,采用比较分子场(CoMFA)和比较分子相似性指数分析(CoMSIA)方法,为新型I_(2)-IR配体双环α-亚氨基膦酸酯类化合物构建了合理的三维定量构象关系(3D-QSAR)模型。结果显示CoMFA和CoMSIA模型具有良好的稳定性和预测能力。根据3D-QSAR模型分析结果进行分子设计并完成活性预测,预测结果印证了分析的合理性,为该系列化合物的结构优化提供了合理建议。The imidazoline I_(2)receptors(I_(2)-IR)has important implications for the treatment of Alzheimer’s disease(AD)and other neurodegenerative diseases.In order to obtain more active I_(2)-IR ligands,a reasonable three-dimensional quantitative conformational relationship(3D-QSAR)model was constructed for the novel I_(2)-IR ligand bicyclicα-iminophosphonates using comparative molecular field(CoMFA)and comparative molecular similarity index analysis(CoMSIA)methods in this paper.The results showed that the CoMFA and CoMSIA models had good stability and predictive ability.Subsequently,the molecular design was carried out and activity prediction was completed based on the results of 3D-QSAR modeling analysis.The prediction results corroborated the rationality of the analysis and provided reasonable suggestions for the structural optimization of this series of compounds.which indicated the reasonableness of the analysis and provided reasonable suggestions for the structural optimization of bicyclicα-iminophosphonate compounds.

关 键 词：咪唑啉I_(2)受体 双环α-亚氨基膦酸酯 3D-QSAR COMFA COMSIA 分子设计 抑制常数 

分 类 号：R914.2[医药卫生—药物化学]