[Three dimensional quantitative structure-activity relationship of heterocyclic-compounds with di-tert-bultylphenyl inhibitors].
OBJECTIVE
To quatitatively disclose the relationship between activity and structure of a new class of COX-II inhibitors containing dialkylphenyl-linked heterocyclic moieties.


RESULTS
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.


CONCLUSIONS
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.
Bai
A P
AP
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Guo
Z R
ZR
Chu
F M
FM
D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006571:Heterocyclic Compounds; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases