Synthesis and anticonvulsant activities ofN-Cbz-α-aminoglutarimidooxy carboxylate derivatives

Abstract

Previous studies on the anticonvulsant activity of N-Cbz-alpha-aminoglutarimides have shown that the derivatives of N-Cbz-alpha-amino-N-alkoxy glutarimide have significant anticonvulsant activity. In addition, their anticonvulsant activities are dependent on the presence of N-alkoxy groups. Based on these results, a series of N-Cbz-alpha-amino-glutarimidooxy carboxylates derivatives (3a-e) were synthesized in moderate yield using a known synthetic procedure. Their anticonvulsant activities were evaluated using the maximal electroshock seizure (MES) test, the pentylene tetrazole induced seizure (PTZ) test, and the strychinine (Str) threshold test with the ultimate aim of developing more active anticonvulsants. None of the compounds (3a-e) tested showed anticonvulsant activity in the MES and PTZ test. However, all the compounds tested exhibited significant anticonvulsant activity in the Str. test. The most active compound in the Str. test was the methyl ester of N-Cbz-alpha-amino-glutarimidooxy acetic acid 3a (ED50 = 42.9 mg/kg).

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

“…1, were reported to exhibit moderate anticonvulsant activities. (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.…”

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).…”