G. Trapani et al., SYNTHESIS AND ANTICONVULSANT ACTIVITY OF SOME 2,3,3A-TETRAHYDROPYRROLO[2,1-B]BENZOTHIAZOL-1-ONES AND PYRROLO[2,1-B]THIAZOLE ANALOGS, European journal of medicinal chemistry, 29(3), 1994, pp. 197-204
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.