SYNTHESIS AND ANTICONVULSANT ACTIVITY OF SOME 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 co mpounds were effective against bicuculline-induced seizures in mice. B inding studies with the prepared compounds using [H-3]flunitrazepam as a ligand for the benzodiazepine receptor and [H-3]muscimol for the ga mma-aminobutyric acid (GABA) receptor, demonstrate that such compounds have no affinity for these recognition sites. On the contrary, some o f 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 o f correlation between the anticonvulsant activity of these compounds a nd their capability to displace [S-35]TBPS binding was observed. Furth ermore, an in vitro study on the most active compound 2a indicates tha t this compound may act intact on its target(s) rather than as a hydro lyzed compound 9.