ANTICONVULSANT ACTIVITY OF VARIOUS ARYL, ARYLIDENE AND ARYLOXYARYL SEMICARBAZONES

A number of aryl, arylidene and aryloxyaryl semicarbazones were evalua ted as candidate anticonvulsants. In particular, insertion of an olefi nic group between the carbimino carbon atom and an aryl ring (referred to as the proximal ring) led to series 6 in which there was retention in activity and 6b,c were shown to be useful lead molecules. At the d oses utilized, neurotoxicity was absent in these compounds when given orally to rats. Attachment of a 2-naphthyloxy group at the 4 position of the proximal ring gave 7 whose high activity in the rat oral maxima l electroshock (MES) screen suggested that the binding site of the sec ond aryl ring was capable of accommodating groups with molecular refra ctivity values of over 40. The greatest activity was displayed by a se ries of aryloxyaryl semicarbazones 8 which had oral activity in the ME S screen substantially greater than phenytoin and with protection indi ces of over 100. A binding site hypothesis formulated as a result of t he biodata generated was in accord with the information obtained by X- ray crystallography. (C) Elsevier, Paris.