The effect of N-alkyloxycarbonyl group on the anticonvulsant activities of N-alkyloxycarbonyl-alpha-aminoglutarimides.

Abstract

In connection with the development of new anticonvulsant agents with a broad spectrum, we reported that N-Cbz-alpha-aminoglutarimides, combining common structures of other anticonvulsants such as N-CO-C-N and cyclic imides in a single molecule, showed significant anticonvulsant activities in the MES (maximal electroshock seizure) and PTZ (pentylenetetrazole induced seizure) tests. In these studies, a series of (R) and (S) N-alkyloxycarbonyl-alpha-aminoglutarimides 7a-7e and 8a-8e, which were substituted with various alkyloxycarbonyl group instead of Cbz group, were prepared from the corresponding (R) and (S) N-Cbz-glutamic acid 3 and 4, and were evaluated with their anticonvulsant activities against the MES and PTZ tests, including neurotoxicity, in order to define the effect of N-alkyloxycarbonyl group on the anticonvulsant activities of N-alkyloxycarbonyl-alpha-aminoglutarimides. Among them, (S) N-4-nitrobenzyloxycarbonyl-alpha-amino-N-methylglutarimide 8e was the most active in MES (ED50 = 35.6 mg/kg, PI = 2.7) and PTZ tests (ED50 = 15.6, PI = 6.1). Interestingly, (R) and (S) N-4-nitrobenzyloxycarbonyl-alpha-amino-N-methylglutarimide 7e and 8e and (R) N-phenoxycarbonyl-alpha-amino-N-methylglutrimide 7d showed significant anticonvulsant activities in both the MES and PTZ tests and other compounds showed anticonvulsant activities in only the PTZ test. In addition, it was found that their anticonvulsant activities were dependent on their stereochemistries and N-substituted alkyloxycarbonyl groups.

• Authors: K Son, K Jung, M Kim, J Lee, J Choi, E Lee, M Park
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 21 Issue 6 Pg. 764-8 (Dec 1998) ISSN: 0253-6269 [Print] Korea (South)
• PMID: 9868553 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants

Topics

• Animals
• Anticonvulsants (chemical synthesis, chemistry, pharmacology, toxicity)
• Injections, Intraperitoneal
• Male
• Mice
• Mice, Inbred ICR