T. Yatabe et al., STUDIES ON 5-LIPOXYGENASE INHIBITORS - I - SYNTHESIS AND 5-LIPOXYGENASE-INHIBITORY ACTIVITY OF NOVEL HYDROXAMIC ACID-DERIVATIVES, Chemical and Pharmaceutical Bulletin, 46(6), 1998, pp. 966-972
A series of novel hydroxamates has been prepared and tested for inhibi
tory activity towards rat polymorphonuclear leukocyte (PMN) 5-lipoxyge
nase (5-LO) in vitro and towards neutrophil migration in the rat air p
ouch model of inflammation in vivo, Many 3,4-dihydronaphthyl compounds
were potent inhibitors of 5-LO, and several compounds were potent inh
ibitors of neutrophil migration, The most potent 3,4-dihydronaphthyl c
ompound, phenoxy)-2-naphthyl]methyl]-N-hydroxy-N'-ethylurea (FR122788,
18) had an IC50 of 25 nM in the 5-LO assay, and strongly reduced neut
rophil migration in the rat air pouch model at 1 mg/kg (p.o.). FR12278
8 also had an ameliorating effect in a rat hepatiatis model induced by
D-galactosamine, with an ED50 values of 14.6 mg/kg (p.o.) for glutama
te oxaloacetate transaminase (GOT) and 16.8 mg/kg (p.o.) for glutamate
pyruvate transaminase (GPT).