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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1989-7-11
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pubmed:abstractText |
The synthesis of a series of 2-(phenylmethyl)-4-hydroxy-3,5-dialkylbenzofurans and their inhibitory effects against leukotriene biosynthesis and 5-lipoxygenase activity in vitro are described. Many compounds in this series were found to be potent inhibitors of LTB4 production by human polymorphonuclear leukocytes with IC50 values ranging from 7 to 100 nM. Structure-activity relationships of the series are presented. Within this series, 2-[(4'-methoxyphenyl)methyl]-4-hydroxy-3-methyl-5-propyl-7-chlorobenz ofuran (L-656,224) showed extremely potent activity, inhibiting leukotriene biosynthesis in intact human leukocytes (IC50 = 11 nM), as well as the 5-lipoxygenase reaction catalyzed by cell-free preparations from rat leukocytes (IC50 = 36 nM), human leukocytes (IC50 = 0.4 microM), and the purified enzyme from porcine leukocytes (IC50 = 0.4 microM). The compound also shows oral activity in a number of animal models in vivo.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
1190-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:2542553-Adult,
pubmed-meshheading:2542553-Animals,
pubmed-meshheading:2542553-Arachidonate Lipoxygenases,
pubmed-meshheading:2542553-Benzofurans,
pubmed-meshheading:2542553-Bronchi,
pubmed-meshheading:2542553-Chemical Phenomena,
pubmed-meshheading:2542553-Chemistry,
pubmed-meshheading:2542553-Constriction, Pathologic,
pubmed-meshheading:2542553-Humans,
pubmed-meshheading:2542553-Immunoglobulin E,
pubmed-meshheading:2542553-Leukocytes,
pubmed-meshheading:2542553-Leukotriene B4,
pubmed-meshheading:2542553-Lipoxygenase Inhibitors,
pubmed-meshheading:2542553-Molecular Structure,
pubmed-meshheading:2542553-Neutrophils,
pubmed-meshheading:2542553-Rats,
pubmed-meshheading:2542553-Rats, Inbred Strains,
pubmed-meshheading:2542553-Structure-Activity Relationship
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pubmed:year |
1989
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pubmed:articleTitle |
Synthesis and structure-activity relationships of a novel class of 5-lipoxygenase inhibitors. 2-(Phenylmethyl)-4-hydroxy-3,5-dialkylbenzofurans: the development of L-656,224.
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pubmed:affiliation |
Department of Medicinal Chemistry, Merck Frosst Canada Inc., Pointe Claire-Dorval, Québec, Canada.
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pubmed:publicationType |
Journal Article,
Comparative Study
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