Synthesis and anticonvulsant activity of N-3-arylamide substituted 5,5-cyclopropanespirohydantoin derivatives

European Journal of Medicinal Chemistry
2010.0

Abstract

In the present study on the development of new anticonvulsants, twenty new N-3-arylamide substituted 5,5-cyclopropanespirohydantoin derivatives were synthesized and tested for anticonvulsant activity using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotorod test. Three compounds 5d, 5j and 5t showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 5j showed the MES-induced seizures with ED50 value of 9.2 mg/kg and TD50 value of 421.6 mg/kg after intraperitoneally injection to mice, which provided compound 5j with a protective index (TD50/ED50) of 45.8 in the MES test.

Knowledge Graph

Similar Paper

Synthesis and anticonvulsant activity of N-3-arylamide substituted 5,5-cyclopropanespirohydantoin derivatives
European Journal of Medicinal Chemistry 2010.0
Synthesis and anticonvulsant activity of ethyl 1-(2-arylhydrazinecarboxamido)-2,2-dimethylcyclopropanecarboxylate derivatives
European Journal of Medicinal Chemistry 2012.0
Design, synthesis, and anticonvulsant activity of N-phenylamino derivatives of 3,3-dialkyl-pyrrolidine-2,5-diones and hexahydro-isoindole-1,3-diones
Bioorganic & Medicinal Chemistry 2008.0
Synthesis and anticonvulsant activity of N-(2-hydroxyethyl) cinnamamide derivatives
European Journal of Medicinal Chemistry 2009.0
Synthesis and anticonvulsant activity of 1-(8-(benzyloxy)quinolin-2-yl)-6-substituted-4,6-diazaspiro[2,4]heptane-5,7-diones
European Journal of Medicinal Chemistry 2012.0
Synthesis and anticonvulsant activity of new N-1′,N-3′-disubstituted-2′H,3H,5′H-spiro-(2-benzofuran-1,4′-imidazolidine)-2′,3,5′-triones
Bioorganic & Medicinal Chemistry Letters 2006.0
Synthesis and anticonvulsant activity of new 6-methyl-1-substituted-4,6-diazaspiro[2.4]heptane-5,7-diones
European Journal of Medicinal Chemistry 2010.0
Synthesis and anticonvulsant activity of new N-Mannich bases derived from 5-cyclopropyl-5-phenyl- and 5-cyclopropyl-5-(4-chlorophenyl)-imidazolidine-2,4-diones
Bioorganic & Medicinal Chemistry 2011.0
Design, synthesis and pharmacological evaluation of novel N-(2-(1, 1-dimethyl-5, 7-dioxo-4, 6-diazaspiro[2.4]heptan-6-yl)ethyl) sulfonamide derivatives as potential anticonvulsant agents
European Journal of Medicinal Chemistry 2015.0
Synthesis and anticonvulsant activity of new N-[(4-arylpiperazin-1-yl)-alkyl] derivatives of 3-phenyl-pyrrolidine-2,5-dione
European Journal of Medicinal Chemistry 2009.0