Discovery of benzothiazine derivatives as novel, orally-active anti-epileptic drug candidates with broad anticonvulsant effect.

In order to develop novel anti-epileptic drugs that are effective for both general and partial seizure, we conducted in vivo screening of our chemical library in the mice MES and sc-PTZ models and found the benzothiazine 1 as lead compound. Optimization of this compound led to the discovery of compound 7b, which showed potent anticonvulsant effect in the MES, scPTZ and rat amygdala kindling models. Since the chemical structure of 7b is different from that of any existing AED, it is suggested that 7b may have unique mechanism of action for relieving both partial and generalized epilepsy.