QSAR STUDIES OF 2-ALKYLBENZIMIDAZOLE DERIVATIVES AS ANGIOTENSIN II RECEPTOR ANTAGONISTS

A set of 14 compounds substituted 2-alkylbenzimidazole derivatives with angiotensin II AT(1) receptor antagonists was subjected to 2-dimensional quantitative structure-activity relationships (2D-QSAR) studies using VLife MDS-3.5 drug designing module with various combinations of thermodynamic, the Baumann alignment independent and spatial descriptors. The statistically significant best 2D-QSAR model was generated by a training set of 10 mol and 4 mol test set with correlation coefficient (r(2)) of 0.9690, significant cross-validated correlation coefficient (q(2)) of 0.8000, F-test of 31.2506, r(2) for external test set (pred_r(2)) 0.9166, coefficient of correlation of predicted data set (pred_r(2)SE) 0.1559 and degree of freedom 4 by multiple linear regression (MLR) method. T_C_O_1, SssCH(3)count, XAHydrophobicArea and slogp descriptors were found to be major contributing descriptors governing the activity. QSAR model validation becomes an essential part in the development of a statistically valid and predictive model, because the real utility of a QSAR model was to design and predict accurately the modelled properties of the newly synthesised compounds as antihypertensive molecules.