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.

Abstract

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.

• Authors: Jolanta Obniska
• Journal: Acta poloniae pharmaceutica (Acta Pol Pharm) 2004 Nov-Dec Vol. 61 Issue 6 Pg. 467-72 ISSN: 0001-6837 [Print] Poland
• PMID: 15794340 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Aza Compounds
• Indicators and Reagents
• Spiro Compounds
• Pentylenetetrazole

Topics

• Animals
• Anticonvulsants (chemical synthesis, pharmacology)
• Aza Compounds (chemical synthesis, pharmacology)
• Dose-Response Relationship, Drug
• Electroshock
• Indicators and Reagents
• Magnetic Resonance Spectroscopy
• Mice
• Pentylenetetrazole
• Postural Balance (drug effects)
• Seizures (chemically induced, prevention & control)
• Spiro Compounds (chemical synthesis, pharmacology)