In vivo Evaluation of Substituted -1H-Pyrrole-2,5- Diones as Anxiolytic-Agents - Abstract
The 3-brominated pyrroldione 1a served as starting material for the preparation of a series of substituted N-methyl 3-amino-pyrrol-2,5-diones, using a Cu catalysed substitution reaction. Initially the newly synthesised compounds were tested at a high dose for CNS depressant activity. When the activity was found significantly different from the control in the rota rod test and the wire mash grasping test at a high dose the active compounds were evaluated further at a low dose in anxiolytic assays. The pyrroldione 2p showed a good anxiolytic activity at low doses of 1/0.1 mg/kg in the light/dark box and the elevated plus-maze assay. The n-hexyl-amino pyrrol 2e served as lead structure for further structure optimisation. Based on 5-alkoxy 3,4-dichloro-2(5H) furanones 3a and 3b, a second series of bis-substituted pyrroldiones was prepared under Cu catalysis and the pyrroldione 4f occurred the most potent anxiolytic activity.