title: Synthesis and anticonvulsant activity of 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, New Drug Discovery Research, Alwar Pharmacy College, Alwar, India.
authors.forename: Mohamed Jawed
authors.initials: MJ
authors.lastname: Ahsan
authors.forename: Habibullah
authors.initials: H
authors.lastname: Khalilullah
authors.forename: James P
authors.initials: JP
authors.lastname: Stables
authors.forename: Jeyabalan
authors.initials: J
authors.lastname: Govindasamy
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004597:Electroshock; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D010433:Pentylenetetrazole / Q000009:adverse effects; D011720:Pyrazoles / Q000737:chemistry; D051381:Rats; D012640:Seizures / Q000188:drug therapy / Q000517:prevention & control
chemical_list: C583377:3-(4-fluorophenyl)-N-(4-bromophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno(1,2-c)pyrazole-2-carboxamide; C583376:3-(pyridin-4-yl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno(1,2-c)pyrazole-2-carboxamide; D000927:Anticonvulsants; D006575:Heterocyclic Compounds, 3-Ring; D011720:Pyrazoles; C031280:pyrazole; D010433:Pentylenetetrazole