王小芳, 黄牛, 屈凌波, 杨光中. NMDA受体甘氨酸位点拮抗剂的三维构效关系研究J. 药学学报, 2000, 35(5): 347-352.
引用本文: 王小芳, 黄牛, 屈凌波, 杨光中. NMDA受体甘氨酸位点拮抗剂的三维构效关系研究J. 药学学报, 2000, 35(5): 347-352.
WANG Xiao-Fang, HUANG Niu, QU Ling-Bo, YANG Guang-Zhong. STUDIES ON THE THREE DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP OF ANTAGONISTS AT THE GLYCINE SITE OF THE N-METHYL-D-ASPARTATE RECEPTORJ. Acta Pharmaceutica Sinica, 2000, 35(5): 347-352.
Citation: WANG Xiao-Fang, HUANG Niu, QU Ling-Bo, YANG Guang-Zhong. STUDIES ON THE THREE DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP OF ANTAGONISTS AT THE GLYCINE SITE OF THE N-METHYL-D-ASPARTATE RECEPTORJ. Acta Pharmaceutica Sinica, 2000, 35(5): 347-352.

NMDA受体甘氨酸位点拮抗剂的三维构效关系研究

STUDIES ON THE THREE DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP OF ANTAGONISTS AT THE GLYCINE SITE OF THE N-METHYL-D-ASPARTATE RECEPTOR

  • 摘要: 目的 建立NMDA受体甘氨酸位点拮抗剂的三维构效关系(3D-QSAR)模型。方法和结果 使用比较分子场分析法(CoMFA)建立的3D-QSAR模型,交叉验证回归系数R2cv、非交叉验证回归系数R2和标准偏差SEE分别为0.650,0.940和0.330,说明系列化合物分子周围立体场和静电场的分布与生物活性间存在良好的相关性。结论 所得模型较好的模拟了受体结合腔穴的立体和静电性质,可用于综合解释已报道的甘氨酸位点拮抗剂构效关系研究结果,并对文献中较少或较模糊的一些区域作了新的探讨,可用来指导设计新的先导物分子。

     

    Abstract: AIM To develop a 3D-QSAR model and gain further insights into the common requirements for the binding of structurally diverse antagonists at the glycine site of the NMDA receptor. METHODS AND RESULTS Based on comparative molecular field analysis(CoMFA), a predictive pharmacophore model was established. The correlation between the activities and structures was significant with cross-validated value(R2cv), non-cross-validated value(R2) and standard error of estimate(SEE) of 0.650, 0.940 and 0.330, respectively. CONCLUSION The obtained model successfully mimics the steric and electrostatic environment around ligands interacting with the receptor. It would contribute to the understanding of the pharmacology of antagonists at the glycine site of the NMDA receptor and direct designation of novel potent lead molecules.

     

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