Quantitative structure-activity relationship of dipeptidyl peptidase IV inhibitors

Dipeptidyl peptidase IV is a critical enzyme of potential value in the treatment of type 2 diabetes. A 3D-QSAR model was obtained by using comparative molecular field analysis (CoMFA) on a series of derivatives N-substituted-glycyl-2-cyanopyrrolidine with highly potent and selective inhibition for dipeptidyl peptidase IV. The final QSAR model was developed by CoMFA analyses, with q(2) = 0.575 and r(2) = 0.981. The predictive ability of this model was validated by seven compounds that were not included in the training set. The robust QSAR model and its three-dimensional contour map provided guidelines to build novel compounds with new scaffold and structural optimization of current molecules.