Saqib_2009_SAR.QSAR.Environ.Res_20_519

Three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses were carried out on 45 triazolopiperazine amide derivatives as dipeptidyl peptidase IV (DPP-IV) inhibitors in order to elucidate their antidiabetic activities. The studies include Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). Models with good predictive abilities were generated with the cross-validated r(2) (r(2)(cv)) and conventional r(2) values of 0.589 and 0.868 for CoMFA and 0.586 and 0.868 for CoMSIA, respectively. Both models were validated by a test set of nine compounds and gave satisfactory predictive r(2) (r(2)(pred)) values of 0.816 and 0.863, respectively. CoMFA and CoMSIA contour maps were then used to analyse the structural features of the ligands to account for the activity in terms of positively contributing physicochemical properties: steric, electrostatic, hydrophobic and hydrogen bond acceptor fields. The information obtained from CoMFA and CoMSIA three-dimensional contour maps can be used for further design of triazolopiperazine amide-based analogues as anti-diabetic agents.