Synthesis and hypnotic activities of N-Cbz-alpha-aminoglutarimidooxy carboxylate derivatives.

Typical hypnotic drugs, such as barbitals and glutethimide, have a cyclic imide (-CO-NH-CO-) moiety. The N-Cbz-alpha-aminoglutarimidooxy carboxylate derivatives, which we previously showed exhibit moderate anticonvulsant activities, also have a cyclic imide (-CO-N-CO-) moiety. This structural similarity prompted us to examine the hypnotic activities of the N-Cbz-alpha-aminoglutarimidooxy carboxylate derivatives, and we describe their moderate hypnotic activities here.

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.

Design and synthesis of 6-amino-1,4-oxazepane-3,5-dione derivatives as novel broad spectrum anticonvulsants.

Based on the structural estimations of the typical anticonvulsant drugs, a series of 6-amino-1,4-oxazepane-3,5-dione derivatives, novel structures of 7-membered heterocyclic imides, which were hybridized with pharmacophores such as cyclic imide and N-CO-C-N group in their molecule were designed and synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock induced seizure (MES) and subcutaneous pentylenetetrazole (PTZ) tests. Almost all the designed compounds except 1c and 1f showed comparable anticonvulsant activities in at least one of the anticonvulsant tests. Moreover, some of the tested compounds exhibited moderate anticonvulsant activities in both MES and PTZ tests. From these results, 6-amino-1,4-oxazepane-3,5-dione derivatives could be recommended as novel structures of broad spectrum anticonvulsants.