Synthesis and anticonvulsant activity of new N-1′,N-3′-disubstituted-2′ H,3 H,5′ H-spiro-(2-benzofuran-1,4′-imidazolidine)-2′,3,5′-triones

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 17; pp. 4644 - 4647
• Main Authors: Patel, Hardik J., Sarra, Joe, Caruso, Francesco, Rossi, Miriam, Doshi, Utkarsh, Stephani, Ralph A.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 2006
• Subjects: 2′ H,3 H,5′ H-spiro-(2-benzofuran-1,4′-imidazolidine)-2′,3,5′-triones anticonvulsants; N,N′-substituted ureas; Ninhydrin; Sodium periodate; Spirohydantoins; Ninhydrin; N,N′-substituted ureas; Spirohydantoins; Sodium periodate; 2′ H,3 H,5′ H-spiro-(2-benzofuran-1,4′-imidazolidine)-2′,3,5′-triones anticonvulsants
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.05.102

The synthesis and anticonvulsant activity of the new phthalidyl spirohydantoins 3d– p is reported, 3o (R 1 = C 2H 5, R 2 = p-NO 2–C 6H 4, X = O) ED 50 = 41.8 mg/kg. Thirteen new N-1′,N-3′-disubstituted-2′ H,3 H,5′ H-spiro-(2-benzofuran-1,4′-imidazolidine)-2′,3,5′-triones were synthesized and their pharmacological activity determined with the objective to better understand their SAR for anticonvulsant activity. The anticonvulsant effects of these compounds were evaluated by standard pentylenetetrazol (scPTZ test) and maximum electroshock seizure (MES test) models in mice. Most of the compounds showed ability to protect against the pentylenetetrazol-induced convulsions. Compound 3o (the N-1′- p-nitrophenyl, N-3′-ethyl derivative) in the N-1′-aryl, N-3′-alkyl disubstituted series exhibited maximum activity with ED 50 of 41.8 mg/kg in scPTZ convulsion model.