Molecular modeling and QSAR analysis of the anticonvulsant activity of some N-phenyl-N′-(4-pyridinyl)-urea derivatives

A quantitative structure activity relationship analysis has been applied to a data set of 20 N-phenyl-N′-(4-pyridinyl)-urea derivatives with anticonvulsant activity. Semi-empirical quantum chemical calculations at AM1 level was used to find the optimum 3D geometry of the studied molecules. Four types of molecular descriptors including classical (substituent constants), constitutional, topological and quantum chemical was used to derive a quantitative relationship between the anticonvulsant activity and structural properties. A multi-parametric equation containing three descriptors with good statistical qualities was obtained using multiple linear regression (MLR). In addition, partial least squares (PLS) regression was used to model the structure-activity relationships, more accurately. The results confirmed the superiority of the results obtained by PLS relative to MLR. The respective percent relative errors of prediction for the MLR and PLS regression methods was between (-3.18)–(+3.15) and (-1.28)–(+1.52). [Copyright &y& Elsevier]