应用比较分子力场法对3-取代的4,6-二氯吲哚-2-甲酸类化合物进行3D-QSAR的研究

应用比较分子力场法对3-取代的4,6-二氯吲哚-2-甲酸类化合物进行3D-QSAR的研究

宋怀恩, 沈建华*, 闻韧*, 蒋华良

1.旦大学药学院药物化学系, 上海 200032;
2.中国科学院上海药物研究所, 上海 201203

收稿日期:2003-11-18 修回日期:2004-05-10 出版日期:2004-06-15 发布日期:2004-06-15
通讯作者: 沈建华*, 闻韧*

A 3D-QSAR Study on C-3 Substituted 4,6-Dichloroindole-2- Carboxylic Acids with Comparative Molecular Field Analysis

SONG Huai-en, SHEN Jian-hua*, WEN Ren*, JIANG Hua-liang

1.Department of Medicinal Chemistry, Fudan University, Shanghai 200032, China;
2.Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

Received:2003-11-18 Revised:2004-05-10 Online:2004-06-15 Published:2004-06-15
Contact: SHEN Jian-hua*, WEN Ren*

摘要/Abstract

摘要： 目的研究一系列新的C-3取代的4,6-二氯吲哚-2-甲酸类化合物的结构和它们与NMDA受体甘氨酸位点亲和活性之间的关系.方法比较分子力场法(CoMFA)是一种三维定量构效关系(3D-QSAR)研究方法.结果所建立模型的交叉验证相关系数q²和非交叉验证相关系数r²分别为0.744和0.993, 标准偏差E = 0.039, F = 261.343.结论所得到的模型对该类化合物的活性会有较好的预测, 用此模型设计的新化合物的活性预测数值也符合我们得到的结论.

关键词: 三维定量构效关系, 三维定量构效关系, 三维定量构效关系, 比较分子力场法分析, 比较分子力场法分析, 比较分子力场法分析, C-3取代4,6-二氯吲哚-2-甲酸, C-3取代4,6-二氯吲哚-2-甲酸, C-3取代4,6-二氯吲哚-2-甲酸, N-甲基-D-天冬氨酸受体, N-甲基-D-天冬氨酸受体, N-甲基-D-天冬氨酸受体

Abstract: Aim and Method Comparative molecular field analysis (CoMFA), a three dimensional quantitative struc-ture-activity relationship (3D-QSAR) method was applied to a novel series of C-3 substituted 4,6-dichloroindole-2-carboxylic acids to study the relationship between their structure and the affinity for the glycine site of the NMDA receptor. Result The coefficients of cross-validation q²and non cross-validation r² for the model established by the study are 0.744 and 0.993, respectively, the value of variance ratio F is 261.343, and standard error estimate (SE) is 0.039. Conclusion These values indicate that the CoMFA model may have a good prediction for the activity of C-3 substituted 4, 6-dichloroin- dole-2-carboxylic acids. As a consequence, the predicted activity values of new designed compoumds supports our conclusion from the model.

Key words: D-QSAR, D-QSAR, CoMFA, CoMFA, C-3 substituted 4,6-dichloroindole-2-carboxylic acids, C-3 substituted 4,6-dichloroindole-2-carboxylic acids, NMDA receptor, NMDA receptor

中图分类号:

R916.2

Supporting: Foundation item: National Natural Science Foundation of China (29872029).
^*Corresponding author. Tel.: 021-54237365

宋怀恩, 沈建华*, 闻韧*, 蒋华良

. 应用比较分子力场法对3-取代的4,6-二氯吲哚-2-甲酸类化合物进行3D-QSAR的研究[J]. .

SONG Huai-en, SHEN Jian-hua*, WEN Ren*, JIANG Hua-liang . A 3D-QSAR Study on C-3 Substituted 4,6-Dichloroindole-2- Carboxylic Acids with Comparative Molecular Field Analysis[J]. .

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