Design of 1-substituted 2-arylmethyl-4,5-methylenedioxybenzene derivatives as antiseizure agents

• Published in: Bioorganic & medicinal chemistry 2004-07, Vol.12 (13), p.3703-3709
• Main Authors: Micale, Nicola, De Sarro, Giovambattista, Ferreri, Guido, Zappalá, Maria, Grasso, Silvana, Puia, Giulia, De Micheli, Carlo
• Format: Article
• Language: English
• Subjects: Animals; Anticonvulsants - chemical synthesis; Anticonvulsants - chemistry; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Benzene - chemical synthesis; Benzene - chemistry; Benzene - pharmacology; Benzene - therapeutic use; Biological and medical sciences; Cells, Cultured; Dioxoles - chemical synthesis; Dioxoles - pharmacology; Dioxoles - therapeutic use; Drug Design; Female; Male; Medical sciences; Mice; Mice, Inbred DBA; Molecular Structure; Neurons - drug effects; Neuropharmacology; Pharmacology. Drug treatments; Seizures - drug therapy; Seizures - physiopathology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2004.04.015

A series of 1-substituted 2-[(4-aryl)-methyl]-4,5-methylenedioxybenzene derivatives were synthesized and sound-induced seizure test was used to evaluate their anticonvulsant activity. A series of 1-substituted 2-[(4-aryl)-methyl]-4,5-methylenedioxybenzene derivatives ( 13– 25), structurally related to model compound 5 (2-[(4-aminophenyl)-(4-methylsemicarbazono)-methyl]-4,5-methylenedioxyphenylacetic acid methyl ester), were synthesized and tested as anticonvulsant agents in DBA/2 mice against sound-induced seizures. The new compounds possess anticonvulsant properties lower than those of prototype 5 but, in some instances, comparable to that of GYKI 52466, a well-known noncompetitive AMPA receptor antagonist.