Synthesis and Anticonvulsant Evaluations ofN-Cbz-α-amino-N-alkoxyglutarimides

Abstract

In our previous studies for the development of new anticonvulsant of broad spectrum, we found that N-cbz-alpha-aminoglutarimides showed significant anticonvulsant activities of broad spectrum enough to be recommended for the new anticonvulsants and their anticonvulsant activities were dependent on their imide substituent groups. Based on these results, various N-cbz-alpha-amino-N-alkoxyglutarimides, where the imide N-H was substituted with the hydroxy and alkoxy group, were prepared and evaluated for their anticonvulsant activities using the Maximal electroshock seizure (MES) and Pentylenetetrazole induced seizure (PTZ) tests and also the rotorod test. A series of (R) or (S)-N-cbz-alpha-amino-N-alkoxyglutarimides could be prepared from the corresponding (R) or (S)-N-cbz-glutamic acid following the usual synthetic procedure. Among them, (R)-N-cbz-alpha-amino-N-hydroxyglutarimide (ED50=86.25 mg/kg) was most active in the MES test. In the case of the PTZ test, (R)-N-cbz-alpha-amino-N-benzyloxyglutarimide (ED50=62.5 mg/kg) was most active. Among the tested compounds, 2a-c, 3a, and 3b showed anticonvulsant activities in the MES and PTZ test. All of the tested compounds, except 2f and 3f, showed significant anticonvulsant activities in the MES or PTZ test. In addition, the neurotoxicities of these compounds were comparable to other anticonvulsant drugs.

Synthesis and anticonvulsant evaluation of 6-amino-1,4-oxazepane-3,5-dione derivatives

“…(Byun et al, 2006;Jung et al, 1998;Kim et al, 2004;Lee et al, 1997Lee et al, , 1999Son et al, 1998) Some of them showed comparable anticonvulsant activities in both of the MES and PTZ tests enough to be recommended as broad spectrum anticonvulsant drug candidates. Kim et al, 2004;Lee et al, 1997Lee et al, , 1999 As seen in Fig. 1, these compounds have either a 5-or a 6-membered α-amino cyclic imide moiety and N-CO-C-N group in their structures.…”

Synthesis and hypnotic activities of N-Cbz-α-aminoglutarimidooxy carboxylate derivatives

“…We previously identified a family of novel anticonvulsants, the N-Cbz-α-aminoglutarimidooxy carboxylate derivatives (Byun et al, 2006;Jung et al, 1998;Kim et al, 2004;Lee et al, 1997;Lee et al, 1999;Son et al, 1998) These compounds can affect the central nervous system (CNS) and have a cyclic imide group (Fig. 2).…”