QSAR APPROACH TO ESTIMATING THE ANALGESIC ACTIVITY OF A SERIES OF TRI-SUBSTITUTED PYRIMIDINE DERIVATIVES
Mamadou Guy-Richard Koné, Yafigui Traoré, Ouanlo Ouattara, Nahossé Ziao · SDRP Journal of Computational Chemistry & Molecular Modelling · 2018
In the search for new molecules with improved analgesic activity, a series of twenty tri-substituted pyrimidine derivatives were subjected to a QSAR study.This study was conducted using Pearson Correlation Coefficients, Principal Component Analysis (PCA), Hierarchical Ascending Classification (HAC) and Multiple Linear Regression.The model obtained correlates the analgesic activity expressed by logAA, the energy of the highest occupied molecular orbital , the dipole moment and the lipophilic coefficient ACD/logP.Statistical indicators R² = 91.55%;RMSE = 0.2592; F = 39.720;= 0.858 and =0.765, establish the internal performance and stability of the model.While its external predictive ability has been proved by the statistical parameters = 0.727 and = 0.403.The domain of applicability of the model developed, determined by the technique of levers and standardized residues, did not present any aberrant observations.The model thus established made it possible to determine the structures of eleven new tri-substituted pyrimidine derivatives having a better analgesic activity than the study molecules, at the dose of 10 mg/kg of body weight.