title: Synthesis and anticonvulsant evaluations of N-cbz-alpha-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.
authors.affiliation: College of Pharmacy, Kyungsung University, 110-1 Daeyeon-Dong, Nam-Gu, Busan 608-736, Korea.
authors.forename: Minjeong
authors.initials: M
authors.lastname: Kim
authors.forename: Aesun
authors.initials: A
authors.lastname: Byun
authors.forename: Jongwon
authors.initials: J
authors.lastname: Choi
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Moon
authors.forename: Chung Kyu
authors.initials: CK
authors.lastname: Lee
authors.forename: Minsoo
authors.initials: M
authors.lastname: Park
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D003292:Convulsants; D004597:Electroshock; D005977:Glutarates / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010433:Pentylenetetrazole; D004856:Postural Balance / Q000187:drug effects
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D005977:Glutarates; D007202:Indicators and Reagents; D010433:Pentylenetetrazole