3D-QSAR studies on fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors by CoMFA and CoMSIA.
Three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses using CoMFA and CoMSIA methods were conducted on a series of fluoropyrrolidine amides as dipeptidyl peptidase IV (DP-IV) inhibitors. The selected ligands were docked into the binding site of the 3D model of DP-IV using the GOLD software, and the possible interaction models between DP-IV and the inhibitors were obtained. Based on the binding conformations of these fluoropyrrolidine amides and their alignment inside the binding pocket of DP-IV, predictive 3D-QSAR models were established by CoMFA and CoMSIA analyses, which had conventional r2 and cross-validated coefficient values ([Formula: see text]) up to 0.982 and 0.555 for CoMFA and 0.953 and 0.613 for CoMSIA, respectively. The predictive ability of these models was validated by six compounds that were in the testing set. Structure-based investigations and the final 3D-QSAR results provide the guide for designing new potent inhibitors.
Zeng
Juan
J
Laboratory of Molecular Modeling & Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
Liu
Guixia
G
Tang
Yun
Y
Jiang
Hualiang
H
D000577:Amides / Q000494:pharmacology; D054873:Dipeptidyl-Peptidase IV Inhibitors; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011759:Pyrrolidines / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
D000577:Amides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011759:Pyrrolidines