In silico studies for the rational discovery of anticonvulsant compounds.

Theoretical models to virtual screening and rational design of anticonvulsant compounds based on a topological substructural molecular design (TOSS-MODE) approach are developed. These models, developed on the basis of data sets of great structural variability, permit the classification of compounds as active/inactive anticonvulsants and predict the quantitative anticonvulsant potency of such compounds. The classification model is applied to a virtual screening of anticonvulsant compounds by analyzing a data set of molecules reported in the literature. More than 88% of them were well classified by the current model. Active and inactive fragments are identified by using the present approach. Some of the active fragments are identified in anticonvulsant molecules as potential pharmacophores and one of them is analyzed in detail. The three-dimensional (3-D) features of this fragment are investigated in a series of five anticonvulsant compounds. Some structure-anticonvulsant activity relationships are derived on the basis of the 3-D structure of this fragment and some findings reported in the literature that indicate that it is an important pharamacophore are outlined.