Validated QSAR analysis of some diaryl substituted pyrazoles as CCR2 inhibitors by various linear and nonlinear multivariate chemometrics methods

被引:29
作者
Arkan, Elham [2 ]
Shahlaei, Mohsen [1 ,3 ]
Pourhossein, Alireza [4 ]
Fakhri, Kambiz [4 ]
Fassihi, Afshin [1 ]
机构
[1] Isfahan Univ Med Sci, Fac Pharm, Dept Med Chem, Esfahan 8174673461, Iran
[2] Univ Tehran Med Sci, Sch Adv Med Technol, Dept Med Nanotechnol, Tehran, Iran
[3] Kermanshah Univ Med Sci, Fac Pharm, Dept Med Chem, Kermanshah, Iran
[4] Kimia Gharb Gostar Ind Co, Ctr Res & Dev, Kermanshah, Iran
关键词
Quantitative structure-activity relationship; Multivariate linear regression; Partial least squares; General regression neural networks; Least squares support vector machine; CCR2; inhibitors; MONOCYTE CHEMOATTRACTANT PROTEIN-1; STRUCTURE-PROPERTY RELATIONSHIP; CHEMOKINE RECEPTORS; EXPRESSION; ANTAGONISTS; REGRESSION; MICE; RECRUITMENT; DEFICIENCY; MODELS;
D O I
10.1016/j.ejmech.2010.04.024
中图分类号
R914 [药物化学];
学科分类号
100705 [微生物与生化药学];
摘要
Quantitative relationships between structures of 26 diaryl substituted pyrazoles as CCR2 inhibitors and their activities were investigated by four linear and nonlinear methods namely MLR, PLS, GRNN and LS-SVM. The obtained models were able to describe about 83%, 87%, 86%. and 0.91% of the variance in the experimental activity of molecules in training set, respectively. The accuracy and predictability of the proposed models were illustrated using various evaluation techniques. Some of them were: cross-validation, validation through an external test set, and Y-randomization. Furthermore, various criteria suggested by Tropsha and Roy were applied for evaluation of predictability of developed models. A comparison between the four different developed methods indicates that LS-SVM can be preferred as supreme model. (C) 2010 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:3394 / 3406
页数:13
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