SYNTHESIS AND ANTICONVULSANT ACTIVITY OF SOME 1,2,3,3A-TETRAHYDROPYRROLO[2,1-B]BENZOTHIAZOL-1-ONES AND PYRROLO[2,1-B]THIAZOLE ANALOGS

Tetrahydropyrrolo[2,1-b]benzothiazol-1-ones 2a-l and its analogues 3a-d were synthesized and tested as anticonvulsant agents. Some of the compounds were effective against bicuculline-induced seizures in mice. Binding studies with the prepared compounds using [H-3]flunitrazepam as a ligand for the benzodiazepine receptor and [H-3]muscimol for the gamma-aminobutyric acid (GABA) receptor, demonstrate that such compounds have no affinity for these recognition sites. On the contrary, some of these compounds reduced, at very high concentrations, the binding of [S-35]-tert-butylbicyclophosphorothionate ([S-35]TBPS) to recognition sites located at the GABA-coupled chloride channel. However, a lack of correlation between the anticonvulsant activity of these compounds and their capability to displace [S-35]TBPS binding was observed. Furthermore, an in vitro study on the most active compound 2a indicates that this compound may act intact on its target(s) rather than as a hydrolyzed compound 9.