Synthesis and anticonvulsant activity of novel imidazol“5(4H)”one and 5-oxo-4,5-dihydroimidazol-1-yl)propanamide derivatives

• Published in: Medicinal chemistry research 2012-12, Vol.21 (12), p.4447-4454
• Main Authors: Khalifa, Maha M. A., Baset, Marawan A., El-Eraky, Wafaa
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Original Research; Pharmacology/Toxicology
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-012-9983-3

(Z)-1-amino-4-(2,4-difluorobenzylidene)-2-(4-fluorophenyl)-imidazol“5(4H)”one 2 was synthesized from the corresponding oxazolone 1 . Condensation with different phenacyl bromide derivatives yielded our target compounds 4-(2,4-difluorobenzylidene)-2-(4-fluorophenyl)-1-(2-oxophenyl/substitutedphenylethylamino)-1H-imidazol“5(4H)”one 3a – f . On the other hand, oxazolone 1 was allowed to react with dl -alanine to obtain (Z)-2-(4-(2,4-difluorobenzylidene)-2-(4-fluorophenyl)-5-oxo-4,5-dihydroimidazol-1-yl)propanoic acid 4 . Chlorination followed by reaction with appropriate aromatic amines gave our compounds 2-(4-(2,4-difluorobenzylidene)-2-(4-fluorophenyl)-5-oxo-4,5-dihydroimidazol-1-yl)- N -phenyl/substitutedphenylpropanamide 6a – c . All the target compounds were evaluated for their anticonvulsant activity using mean electroshock (MES) test at an oral dose of 100 mg/Kg. Most of the compounds showed protection against seizures with a potency ranging from 70 to 96%. However, compounds 3d , 6b , and c showed excellent protection against seizures with a potency of 92.84, 96.42, 96.42%, respectively, with respect to the reference standard phenytoin with a potency of 100%. To assess the locomotor coordination and neurological deficit, animals were tested on the rotarod, the most promising compounds did not affect the stability of mice on rotarod at the same dose level.