Substituted 2-Benzothiazolamines as Sodium Flux Inhibitors: Quantitative Structure-Activity Relationships and Anticonvulsant Activity

摘要: Thirty-two aryl-substituted 2-benzothiazolamines have been tested for their ability to modulate sodium flux in rat cortical slices. A QSAR analysis, applied these derivatives, showed a trend toward increasing potency as inhibitors with lipophilicity, decreasing size, and electron withdrawal of the benzo ring substitutents. Additionally, 4- or 5-substitution was found decrease potency. The combination increased small severely limited which groups were tolerated on ring, thus suggesting that optimal substitution patterns prepared within this series. Nine compounds potent veratridine-induced (NaFl). These nine also proved be anticonvulsant maximal electroshock (MES) assay. Fourteen additional demonstrated activity MES screen, yet exhibited no NaFl derivatives may interacting at channel manner not discernible by paradigm, they acting an alternative mechanism vivo.