QSAR studies on triazole derivatives as sglt inhibitors via CoMFA and CoMSIA.

Forty-six sodium-dependent glucose cotransporters-2 (SGLT-2) inhibitors with hypoglycemic activity were selected to develop three-dimensional quantitative structure-activity relationship (3D-QSAR) using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. A training set of 39 compounds were used to build up the models, which were then evaluated by a series of internal and external cross-validation techniques. A test set of 7 compounds was used for the external validation. The CoMFA model predicted a q 2 value of 0.792 and an r 2 value of 0.985. The best CoMSIA model predicted a q 2 value of 0.633 and an r 2 value of 0.895 based on a combination of steric, electrostatic, hydrophobic and hydrogen-bond acceptor effects. The predictive correlation coefficients ( r pred 2 ) of CoMFA and CoMSIA models were 0.872 and 0.839, respectively. The analysis of the contour maps from each model provided insight into the structural requirements for the development of more active sglt inhibitors, and on the basis of the models 8 new sglt inhibitors were designed and predicted. [ABSTRACT FROM AUTHOR]