Synthesis and anticonvulsant properties of a series of N-substituted 2-aza-spiro[4.5]decane-1,3-diones and 8-phenyl-2-aza-spiro[4.5]decane-1,3-diones.
A series of N-phenyl-2-aza-spiro[4.5]decane-1,3-diones [III-VIIII] structurally related to the previously described N-phenyl-3-arylpyrrolidine-2,5-dione (11) was synthesized and tested for their anticonvulsant activity in the maximum electroshock seizure (MES) and metrazole seizure threshold (sc. MET) tests. The most potent of the series were N-(2-methylphenyl)-2-aza-spiro[4.5]decane-1,3-dione [III] and N-(3-methylphenyl)-2-aza-spiro [4.5]decane-1,3-dione [IV], which inhibited seizures in the MES and sc.MET tests. On the other hand, as a preliminary assay we synthesized and tested for the anticonvulsant activity a new N-substituted 8-phenyl-2-aza-spiro[4.5]decane-1,3-dione, containing either a benzyl or a cyclohexyl moiety [IX-XII] at the nitrogen atom. The obtained results showed that the presence and position of the methyl group in the aryl ring [III, IV], as well as an cyclohexane moiety [XI, XIII connected with the imide nitrogen atom, played the essential role for anticonvulsant activity.
Obniska
Jolanta
J
Department of Pharmaceutical Chemistry, Collegium Medicum Jagiellonian University, 30-688 Kraków, Poland.
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010433:Pentylenetetrazole; D004856:Postural Balance / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*
D000927:Anticonvulsants; D001372:Aza Compounds; D007202:Indicators and Reagents; D013141:Spiro Compounds; D010433:Pentylenetetrazole