Three dimensional quantitative structure-activity relationship of heterocyclic-compounds with di-tert-bultylphenyl inhibitors
Bai, A.P.; Guo, Z.R.; Chu, F.M.
Yao Xue Xue Bao 36(5): 347-350
2001
ISSN/ISBN: 0513-4870 PMID: 12584856 Document Number: 526939
To quatitatively disclose the relationship between activity and structure of a new class of COX-II inhibitors containing dialkylphenyl-linked heterocyclic moieties. Seventeen COX-II inhibitors from literature as a training set were investigated with the aim of developing a 3D-QSAR model using comparative molecular field analysis (CoMFA). To reveal the pharmacophoric pattern, several modes of superimposition were explored. The significant model shows a higher ability to explain and predict the activity of COX-II inhibitors, with the cross-validation RCV2 = 0.718, non cross-validation R2 = 0.992, F = 260,624, and SEE (standard error of estimate) = 0.072. Three compounds were selected as a predicting set, the low deviations of calculated values from the measured ones suggesting a powerful predictive ability of the model. The 3D-QSAR explains the dependence of COX-2 inhibition upon the structures of the compounds. Some structure information for design of new COX-II inhibitors with higher activity has been given.