Synthesis and anticonvulsant activity of 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues

A series of fourteen 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues were synthesized and evaluated for anticonvulsant activity according to the Antiepileptic Drug Development Programme (ADD) protocol. Some of the synthesized compounds showed significant activity in minimal clonic seizure model (6 Hz psychomotor seizure test). 3-(4-Fluorophenyl)-N-(4-bromophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (4c) was found to be the most active compound of the series showing 75% (3/4, 0.25-2.0 h) and 50% (2/4, 4.0 h) protection against minimal clonic seizure at 100 mg/kg without any toxicity. 3-(Pyridin-4-yl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (4f) showed protection in maximal electroshock (MES) seizure and subcutaneous metrazol (scMET) seizure at 300 mg/kg.