Synthesis and Antiepileptic Evaluation of Some New Thiophene Incorporated 1,5-Benzothiazepine Derivatives

Epilepsy is a chronic neurological disorder affecting approximately 50 million individuals worldwide. It poses a significant challenge like osteoporosis, Stevens-Johnson syndrome, agranulocytosis, aplastic anemia, hepatic failure, pancytopenia, multiorgan hypersensitivity, and psychosis due to limited efficacy of currently available antiepileptic drugs (AEDs). The heterocyclic rings thiophene and 1,5-benzothiazepine have been studied extensively for their antiepileptic activity. This study synthesized a series of new thiophene-incorporated 1,5-benzothiazepine derivatives. The synthetic technique involved the condensation of ketomethylene with malononitrile to form a Knoevenagel–Cope condensation product, which cyclizes with sulfur and diethyl amine to give a 2-aminothiophene derivative. This forms thienyl chalcones upon treatment with different substituted benzaldehyde in ethanol and sodium hydroxide as a base at room temperature. Upon refluxing with o-amino thiophenol, these chalcones form corresponding thiophene-incorporated benzothiazepine derivatives. The structure of these compounds was confirmed by IR, ¹H NMR, and Mass spectroscopy. Compound TBA5 was subjected to in vivo antiepileptic activity by Maximal electroshock induced seizure and Pentylenetetrazole induced seizure model. Compound TBA5, in three different dosage levels (low, medium, high), effectively decreased convulsions compared to the control. Hence, the findings highlight the potential of the newly designed compound TBA5 as a viable option for further exploration as an antiepileptic medication.