QSAR Modeling of Compounds Derived from 1,2,3-Triazolopiperidine as DPP-4 Enzyme Inhibitors Using Semiempirical AM1

Abstract

<p>This study aims to model the derived compounds of 1,2,3-triazolopiperidine using sem­iempirical method AM1 and determine the further derivation with the better IC<sub>50</sub> values against DPP-4 enzyme theoretically. This research employed ChemDraw Pro 12 software for for 2D struc­tural drawing, Hyperchem 8.0 for 3D modelling, and MLR statistical analysis for modeling QSAR equations. The semiempirical method was likely to be the appropriate platform to apply because the correlation coefficient of H<sup>1 </sup>NMR chemical shift between theoretical and actual value is rela­tively close, 0.8891. The multilinear regression analysis produced 4 equation models where the best one is equation 4 as detailed below:” IC<sub>50</sub> = 875,5116 + (-7400,27*qH35) + (-0,00133* Eat.is) + (-3230,72* qN23) + (3,30277* µ)” n = 25; r<sup>2</sup> = 0,594; <em>Adjusted r<sup>2</sup></em>= 0,486; PRESS = 1,2× 10<sup>4</sup><sup>. </sup>Finally, the theoretically promising substituent was -CN possessing IC<sub>50</sub> value = 1.61 nM. </p>