3D QSAR comparative molecular field analysis on nonsteroidal farnesoid X receptor activators.
Three-dimensional quantitative structure-activity relationships (3D QSAR) were performed for a series of farnesoid X receptor activators using comparative molecular field analysis (CoMFA). A training set containing 77 compounds served to establish the models. The best statistical results among all models were obtained with region focusing weighted by a S.D. x coefficient values of 0.8 and a grid spacing of 1.0 (r2=0.963, SEE=0.097; q2=0.742, SEP=0.255). The model was used to predict the potency of 20 test set compounds that were not included in the training set, and the predicted values were in good agreement with the experimental results. The final CoMFA model along with the information obtained from 3D contour maps should be useful for the design of novel FXR ligands having improved potency.
Honório
Káthia M
KM
Laboratório de Química Medicinal e Computacional, Centro de Biotecnologia Molecular Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo, Av. Trabalhador São-Carlense, 400, 13560-970 São Carlos, SP, Brazil.
Garratt
Richard C
RC
Polikarpov
Igor
I
Andricopulo
Adriano D
AD
D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000819:agonists*; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013678:Technology, Pharmaceutical / Q000379:methods; D014157:Transcription Factors / Q000819:agonists*; D000099150:Receptor, Farnesoid X-Activated
D004268:DNA-Binding Proteins; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated