Sulfamides as new targets for anticonvulsant drugs: Design, Synthesis and Evaluation.

GAVERNET LUCIANA; BARRIOS IVANA A.; ELVIRA JUAN E.; PASTORE VALENTINA; SAMAJA GISELA; BRUNO-BLANCH LUIS E.

Chicago, Estados Unidos

Congreso; 233rd American Chemical Society National Meeting & Exposition; 2007

sulfamide functionality were designed, synthesized, and tested in their ability to suppress experimentally induced convulsions in laboratory animals. The design was based on a three-dimensional quantitative structure-activity relationship method, the Comparative Molecular Field Analysis (CoMFA). The training set (27 structures) was comprised of traditional and new generation anticonvulsant drugs. The results, together with bioisosteric considerations, pointed to sulfamides as new lead structures, which also comply with the polar requirements imposed by a previously identified pharmacophore. Following the design, 27 sulfamides and sulfamide derivatives were synthesized and tested for activity in the maximal electroshock (MES) test, which is mainly used to target inhibition of the neuronal voltage-dependent Na channels.