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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1990-2-22
|
| pubmed:abstractText |
Four series of N-[(arylmethoxy)phenyl] compounds were prepared as leukotriene D4 (LTD4) antagonists. In the hydroxamic acid series, methyl 3-(2-quinolinylmethoxy)benzeneacetohydroxamate (Wy-48,422, 20) was the most potent inhibitor of LTD4-induced bronchoconstriction with an oral ED50 of 7.9 mg/kg. Compound 20 also orally inhibited ovalbumin-induced bronchoconstriction in the guinea pig with an ED50 of 3.6 mg/kg. In vitro, against LTD4-induced contraction of isolated guinea pig trachea pretreated with indomethacin and 1-cysteine, 20 produced a pKB value of 6.08. In the sulfonyl carboxamide series, N-[(4-methylphenyl)sulfonyl]-3-(2-quinolinylmethoxy)-benzamide (Wy-49,353, 30) was the most potent antagonist. Compound 30 orally inhibited both LTD4- and ovalbumin-induced bronchoconstriction with ED50s of 0.4 and 20.2 mg/kg, respectively. In vitro, against LTD4-induced contraction of isolated guinea pig trachea, 30 produced a pKB value of 7.78. In the carboxylic acid series, which served as intermediates for the above two series, 3-(2-quinolinylmethoxy)benzeneacetic acid (Wy-46,016, 5) was the most potent inhibitor of LTD4-induced bronchoconstriction (99% at 25 mg/kg, intraduodenally); however, the pKB for this compound was disappointing (5.79). In the tetrazole series, the most potent inhibitor was 2-[[3-(1H-tetrazol-5-ylmethyl)phenoxy]methyl]quinoline (Wy-49,451, 41). The respective inhibitory ED50s were 3.0 mg/kg versus LTD4 and 17.5 mg/kg versus ovalbumin. In the isolated guinea pig trachea, 41 produced a pKB value of 6.70.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Azoles,
http://linkedlifedata.com/resource/pubmed/chemical/Benzamides,
http://linkedlifedata.com/resource/pubmed/chemical/Carrageenan,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ovalbumin,
http://linkedlifedata.com/resource/pubmed/chemical/Quinolines,
http://linkedlifedata.com/resource/pubmed/chemical/SRS-A,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrazoles
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
33
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
240-5
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:2104935-Animals,
pubmed-meshheading:2104935-Azoles,
pubmed-meshheading:2104935-Benzamides,
pubmed-meshheading:2104935-Biological Assay,
pubmed-meshheading:2104935-Bronchial Spasm,
pubmed-meshheading:2104935-Carrageenan,
pubmed-meshheading:2104935-Chemical Phenomena,
pubmed-meshheading:2104935-Chemistry,
pubmed-meshheading:2104935-Cyclooxygenase Inhibitors,
pubmed-meshheading:2104935-Edema,
pubmed-meshheading:2104935-Guinea Pigs,
pubmed-meshheading:2104935-Hydroxamic Acids,
pubmed-meshheading:2104935-Lipoxygenase Inhibitors,
pubmed-meshheading:2104935-Molecular Structure,
pubmed-meshheading:2104935-Muscle Contraction,
pubmed-meshheading:2104935-Neutrophils,
pubmed-meshheading:2104935-Ovalbumin,
pubmed-meshheading:2104935-Quinolines,
pubmed-meshheading:2104935-Rats,
pubmed-meshheading:2104935-SRS-A,
pubmed-meshheading:2104935-Structure-Activity Relationship,
pubmed-meshheading:2104935-Tetrazoles,
pubmed-meshheading:2104935-Trachea
|
| pubmed:year |
1990
|
| pubmed:articleTitle |
N-[(arylmethoxy)phenyl] carboxylic acids, hydroxamic acids, tetrazoles, and sulfonyl carboxamides. Potent orally active leukotriene D4 antagonists of novel structure.
|
| pubmed:affiliation |
Wyeth-Ayerst Research, Princeton, New Jersey 08543-8000.
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| pubmed:publicationType |
Journal Article
|