Synthesis and anticonvulsant evaluation of 6-amino-1,4-oxazepane-3,5-dione derivatives.
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.
Sharma
Gitalee
G
College of Pharmacy, Kyungsung University, Busan, Korea.
Park
Jin Yup
JY
Park
Min Soo
MS
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D003292:Convulsants; D004597:Electroshock; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010077:Oxazepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D010433:Pentylenetetrazole; D014635:Valproic Acid / Q000494:pharmacology
C531282:6-amino-1,4-oxazepane-3,5-dione; D000927:Anticonvulsants; D003292:Convulsants; D007202:Indicators and Reagents; D010077:Oxazepines; D014635:Valproic Acid; D010433:Pentylenetetrazole