Studies on 5-lipoxygenase inhibitors. I. Synthesis and 5-lipoxygenase-inhibitory activity of novel hydroxamic acid derivatives.
Chem Pharm Bull (Tokyo)
; 46(6): 966-72, 1998 Jun.
Article
em En
| MEDLINE
| ID: mdl-9658575
ABSTRACT
A series of novel hydroxamates has been prepared and tested for inhibitory activity towards rat polymorphonuclear leukocyte (PMN) 5-lipoxygenase (5-LO) in vitro and towards neutrophil migration in the rat air pouch model of inflammation in vivo. Many 3,4-dihydronaphthyl compounds were potent inhibitors of 5-LO, and several compounds were potent inhibitors of neutrophil migration. The most potent 3,4-dihydronaphthyl compound, N-[[(3,4-dihydro-5-phenoxy)-2-naphthyl]methyl]-N-hydroxy-N'-ethylurea (FR122788, 18) had an IC50 of 25 nM in the 5-LO assay, and strongly reduced neutrophil migration in the rat air pouch model at 1 mg/kg (p.o.). FR122788 also had an ameliorating effect in a rat hepatitis model induced by D-galactosamine, with an ED50 values of 14.6 mg/kg (p.o.) for glutamate oxaloacetate transaminase (GOT) and 16.8 mg/kg (p.o.) for glutamate pyruvate transaminase (GPT).
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ureia
/
Anti-Inflamatórios não Esteroides
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Inibidores de Lipoxigenase
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Quinases da Família src
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Ácidos Hidroxâmicos
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Naftalenos
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Neutrófilos
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Chem Pharm Bull (Tokyo)
Ano de publicação:
1998
Tipo de documento:
Article