物理化学学报 >> 2004, Vol. 20 >> Issue (05): 488-493.doi: 10.3866/PKU.WHXB20040509

研究论文 上一篇    下一篇

GABAA五种亚型受体与BZ配基的3D-QSAR研究

陆爱军;刘冰;刘海波;周家驹   

  1. 中国科学院过程工程研究所,北京　100080
  • 收稿日期:2003-11-14 修回日期:2003-12-21 发布日期:2004-05-15
  • 通讯作者: 周家驹 E-mail:jjzhou@lcc.icm.ac.cn

3D-QSAR Study of Benzodiazepines at Five Recombinant GABAA/Benzodiazepine Receptor Subtypes

Lu Ai-Jun;Liu Bing;Liu Hai-Bo;Zhou Jia-Ju   

  1. Institute of Process Engineering, Chinese Academy of Sciences, Beijing　100080
  • Received:2003-11-14 Revised:2003-12-21 Published:2004-05-15
  • Contact: Zhou Jia-Ju E-mail:jjzhou@lcc.icm.ac.cn

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摘要： GABAA受体是中枢神经系统内重要的抑制性受体，有广泛的神经生理活性.由于镇静/抗惊厥药物在临床上的广泛应用，使得其中苯并二氮杂作用位点尤为重要.我们用比较分子场法(CoMFA)对一系列咪唑苯并二氮杂类化合物（BZ）与五种重组受体亚型的亲和力进行了结构活性关系研究，得到的一组模型都有较高的交叉验证系数.并在此基础上，建立了非交叉验证的一组PLS模型.用该组模型对随机选择的6个化合物组成的测试集进行了预测，都得到了相当满意的结果，表明所建立的一组模型具有良好的预测能力.本研究对于设计高亲和力的BZ受体的配基和研究GABAA受体的模型有指导意义.

关键词: 比较分子力场分析(CoMFA), 苯并二氮杂类化合物(BZ), GABAA受体

Abstract: GABAA receptor is the major neurotransmitter system in the central nervous system(CNS) and elicits a wide range of neuronal physiological activities. Since anxiolytic/anticonvulsant agents have been employed widely in clinic, the receptor sites for the benzodiazepine are of prime importance. Studies on quantitative structure-activity relationship with CoMFA for the binding affinities of a series of imidazobenzodiazepines at five recombinant receptor subtypes were carried out successfully, and a good crossvalidated correlation was obtained for each receptor subtype. Then a set of non-cross-validated PLS models was built and permitted demonstration of high predictability for the affinities of the six ligands in the test set selected in random at all five receptor subtypes. The modals can help design high affinitiy ligands on the GABAA/BZ receptor and understand the GABAA receptor modal.

Key words: Comparative mo1ecular field analysis(CoMFA), Benzodiazepine(BZ), 　GABAA receptor