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Titolo:
N-(BENZYLOXYCARBONYL)GLYCINE ESTERS AND AMIDES AS NEW ANTICONVULSANTS
Autore:
GEURTS M; POUPAERT JH; SCRIBA GKE; LAMBERT DM;
Indirizzi:
UNIV CATHOLIQUE LOUVAIN,FAC MED,SCH PHARM,DEPT PHARMACEUT SCI,LAB PHARMACEUT CHEM & RADIOPHARM B-1200 BRUSSELS BELGIUM UNIV CATHOLIQUE LOUVAIN,FAC MED,SCH PHARM,DEPT PHARMACEUT SCI,LAB PHARMACEUT CHEM & RADIOPHARM B-1200 BRUSSELS BELGIUM UNIV MUNSTER,DEPT PHARMACEUT CHEM D-48149 MUNSTER GERMANY
Titolo Testata:
Journal of medicinal chemistry
fascicolo: 1, volume: 41, anno: 1998,
pagine: 24 - 30
SICI:
0022-2623(1998)41:1<24:NEAAAN>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
N-BENZYLOXYCARBONYLGLYCINE; ENKEPHALINASE INHIBITOR; GLYCINE-BINDING; NMDA RECEPTOR; MICE; LIPOPHILICITY; SITE; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
M. Geurts et al., "N-(BENZYLOXYCARBONYL)GLYCINE ESTERS AND AMIDES AS NEW ANTICONVULSANTS", Journal of medicinal chemistry, 41(1), 1998, pp. 24-30

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 theMES 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 ip 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, are potent anticonvulsant agents.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/07/20 alle ore 06:39:23