SUBSTITUTED ARYLMETHYL PHENYL ETHERS .1. A NOVEL SERIES OF 5-LIPOXYGENASE INHIBITORS AND LEUKOTRIENE ANTAGONISTS

被引:59
作者
MUSSER, JH [1 ]
CHAKRABORTY, UR [1 ]
SCIORTINO, S [1 ]
GORDON, RJ [1 ]
KHANDWALA, A [1 ]
NEISS, ES [1 ]
PRUSS, TP [1 ]
VANINWEGEN, R [1 ]
WEINRYB, I [1 ]
COUTTS, SM [1 ]
机构
[1] REVLON HLTH CARE GRP, DIV RES & DEV, TUCKAHOE, NY 10707 USA
关键词
D O I
10.1021/jm00384a017
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of new substituted arylmethyl phenyl ethers has been prepared. These compounds were tested as inhibitors of 5-lipoxygenase (5-LO) in rat neutrophils, in vitro antagonists of leukotriene-induced contraction of guinea pig (GP) lung parenchymal strips, and inhibitors of slow reacting substance of anaphylaxis (SRS-A) mediated bronchospasm in the GP in vivo. Most representatives of this new class of potential antiallergic/antiinflammatory agents showed potent inhibition of 5-LO activity in rat PMNs. The most potent compound, 2-[[3-(1-hydroxyhexyl)phenoxy]-methyl]quinoline (33), had an I50 of 0.12 .mu.M in the rat PMN 5-LO assay and an I50 of 3.6 .mu.M in the leukotriene-induced contraction of GP lung parenchymal strips, and it also showed 91% inhibition of SRS-A-mediated bronchospasm in the GP in vivo at 10 mg/kg, administered intraduodenally. Some of the compounds in this series were also leukotriene antagonists in vitro, and several of them showed in vivo activity against SRS-A-mediated bronchospasm in the GP.
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页码:96 / 104
页数:9
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