Pharmacophoric pattern of anti-epileptic sulfonamides and sulfamates.: Theoretical study of the associated requirements

A pharmacophoric pattern of sulfonamides is presented, which concerns compounds structurally related to Topiramate (Top) with anti-convulsant activity against the maximal electroshock seizure (MES test). The pharmacophore is characterized by a polar sulfonamide group, whose descriptors are analyzed in order to discern the associated requirements. It has been derived from a conformational study, based on a quantum-chemical calculations, followed by a similarity analysis that include structures synthesized and tested in our lab, together with drugs that are already in clinical use. Different possible mechanisms of action are compared, including carbonic anhydrase inhibition. (C) 2002 Elsevier Science B.V. All rights reserved.