Synthesis and Anticonvulsant Evaluation of 6-Amino-1,4-oxazepane-3,5-dione Derivatives

• Published in: Archives of pharmacal research 2008, Vol.31 (7), p.838-842
• Main Authors: Sharma, Gitalee, Park, Jin-Yup, Park, Min-Soo
• Format: Article
• Language: Korean
• ISSN: 0253-6269; 1976-3786

The N-Acyl-$\alpha$-aminosuccinimides and N-Acyl-$\alpha$-aminoglutarimides were reported to exhibit moderate anticonvulsant activities. These compounds were 5-membered or 6-membered $\alpha$- amino cyclic imides and have N-CO-C-N moiety in their structures. Based on these structural characteristics, a series of 6-amino-1,4-oxazepine-3,5-dione derivatives 1, having a heterocyclic 7-memberd $\alpha$-amino cyclic imide and N-CO-C-N moiety in their structures were designed and synthesized. These syntheses were in view to develop novel anticonvulsant compounds. The 6-amino-1, 4-oxazepine-3,5-dione derivatives were prepared from (S)-N-Cbz-serine by usual synthetic procedures and their anticonvulsant activities were examined by the MES and PTZ tests. The N-H (1a), N-methyl (1b), and N-n-butyl (1e) derivatives showed moderate anticonvulsant activities in the MES test. In the case of PTZ test, all the tested compounds except N-n-propyl compound(1c) also showed moderate anticonvulsant activities. Moreover, N-H (1a), N-methyl (1b), and N-n-butyl (1e) derivatives showed anticonvulsant activities in both the MES and PTZ test. From these studies, it was concluded that the 6-amino-1,4-oxazepane-3,5-dione derivatives were novel compounds enough to be recommended as new anticonvulsants.