3D QSAR studies on 1, 3, 4-thiadiazole derivatives: an approach to design novel anticonvulsants

A three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on a series of 1, 3, 4-thiadiazole derivatives reported as anticonvulsant employing self-organizing molecular field analysis (SOMFA) techniques to investigate the structural requirements for the design of novel anticonvulsant. The training set composed of twenty two 1, 3, 4-thiadiazole derivatives that exhibit a potent activity in MMS test while predictive power was evaluated using a test set of 7 molecules. Physicochemical determinants of binding, such as steric and electrostatic properties, were mapped onto the molecular structures of 1, 3, 4-thiadiazole in order to interpret graphically the SOMFA results in terms of master grids showing various field contributions. The present 3D-QSAR studies yielded stable and statistically robust models indicated by the moderate cross correlation coefficients which may prove to be a guideline for design of novel anticonvulsants.