Synthesis and anticonvulsant activities of N-Cbz-alpha-aminoglutarimidooxy carboxylate derivatives.
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).
Byun
Aesun
A
College of Pharmacy, Kyungsung University, Busan, Korea.
Choi
Jong Won
JW
Moon
Kyung Ho
KH
Lee
Chung Gyu
CG
Park
Min Soo
MS
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010881:Piperidones / Q000138:chemical synthesis / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D013331:Strychnine
D000927:Anticonvulsants; D002264:Carboxylic Acids; D010881:Piperidones; D013331:Strychnine; C007864:glutarimide