N-(benzyloxycarbonyl)glycine esters and amides as new anticonvulsants

Journal of Medicinal Chemistry
M GeurtsD M Lambert

Abstract

Glycine is a small neutral amino acid exhibiting weak anticonvulsant activities in vivo. Recently, studies have demonstrated that N-(benzyloxycarbonyl)glycine (1) antagonized seizures superior to glycine in addition to activity in the maximal electroshock (MES) test, a convulsive model where glycine is inactive. In the present study a series of ester and amide derivatives of 1 as well as esters of N-(3-phenylpropanoyl)glycine (5) have been prepared. The compounds were evaluated in the MES test as well as in several chemically induced seizure models. Among the derivatives investigated, N-(benzyloxycarbonyl)glycine benzylamide (16) was the most potent compound exhibiting an anticonvulsant activity in the MES test comparable to the drug phenytoin. Median effective doses (ED50) of 4.8 and 11.6 mg/kg were determined at 30 min and 3 h after i.p. administration, respectively. Compound 16 also effectively suppressed tonic seizures in different chemically induced models such as the strychnine, 3-mercaptopropionic acid, and pentylenetetrazole tests. Moreover, the compound studied here did not show acute neurotoxicity in the rotorod test up to a dose of 150 mg/kg. It is concluded that N-(benzyloxycarbonyl)glycine amides, especially 16, ar...Continue Reading

References

Apr 1, 1975·The Journal of Physiology·G BañosO E Pratt
Nov 1, 1992·Quarterly Reviews of Biophysics·H Betz
Jun 1, 1992·Pharmacology, Biochemistry, and Behavior·C BeyerM Caba
Oct 1, 1970·Journal of Neurochemistry·R P Shank, M H Aprison
Mar 1, 1983·Neurochemical Research·E TothN Seiler
Jan 1, 1984·Cleveland Clinic Quarterly·R J PorterB G White
Jan 1, 1984·General Pharmacology·N Seiler, S Sarhan
Nov 25, 1994·Journal of Medicinal Chemistry·P D Leeson, L L Iversen
Oct 19, 1993·European Journal of Pharmacology·D M LambertP Dumont
Apr 26, 1996·Journal of Medicinal Chemistry·D ChoiH Kohn
Dec 1, 1995·Journal of Pharmaceutical Sciences·R MannholdE E Polymeropoulos

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Citations

Oct 18, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·D M Lambert
Mar 28, 2003·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Giuseppe TrapaniGaetano Liso
Jan 8, 2015·Seizure : the Journal of the British Epilepsy Association·Eunice S M Yuen, Iñaki F Trocóniz
Feb 12, 2009·Chemical Biology & Drug Design·Lei ZhangZhe-Shan Quan
Jul 20, 1999·The Journal of Pharmacy and Pharmacology·G K Scriba, D M Lambert
Dec 6, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hong-Jian ZhangZhe-Shan Quan
Jul 28, 2004·European Journal of Medicinal Chemistry·Perumal YogeeswariDharmarajan Sriram
Jun 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tarek S IbrahimMohamed Elagawany
Oct 20, 2009·Bioorganic & Medicinal Chemistry Letters·Rolando Perez-PineiroDavid S Wishart

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