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rdf:type |
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|
lifeskim:mentions |
|
|
pubmed:issue |
4
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|
pubmed:dateCreated |
2000-3-16
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|
pubmed:abstractText |
A novel series of heteroarylmethoxyphenylalkoxyiminoalkylcarboxylic acids was studied as leukotriene biosynthesis inhibitors. A hypothesis of structure-activity optimization by insertion of an oxime moiety was investigated using REV-5901 as a starting point. A systematic structure-activity optimization showed that the spatial arrangement and stereochemistry of the oxime insertion unit proved to be important for inhibitory activity. The promising lead, S-(E)-11, inhibited LTB(4) biosynthesis in the intact human neutrophil with IC(50) of 8 nM and had superior oral activity in vivo, in a rat pleurisy model (ED(50) = 0.14 mg/kg) and rat anaphylaxis model (ED(50) = 0.13 mg/kg). In a model of lung inflammation, S-(E)-11 blocked LTE(4) biosynthesis (ED(50) of 0.1 mg/kg) and eosinophil influx (ED(50) of 0.2 mg/kg). S-(E)-11 (A-93178) was selected for further preclinical evaluation.
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pubmed:language |
eng
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pubmed:journal |
|
|
pubmed:citationSubset |
IM
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|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
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|
pubmed:month |
Feb
|
|
pubmed:issn |
0022-2623
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|
pubmed:author |
pubmed-author:BellR LRL,
pubmed-author:BhatiaPP,
pubmed-author:BouskaJ BJB,
pubmed-author:BrooksC DCD,
pubmed-author:CarterG WGW,
pubmed-author:GamsEE,
pubmed-author:GunnD EDE,
pubmed-author:HarrisR RRR,
pubmed-author:HulkowerK IKI,
pubmed-author:KolasaTT,
pubmed-author:MaloP EPE,
pubmed-author:StewartA OAO,
pubmed-author:WoodsK WKW
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|
pubmed:issnType |
Print
|
|
pubmed:day |
24
|
|
pubmed:volume |
43
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
690-705
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|
pubmed:dateRevised |
2006-11-15
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|
pubmed:meshHeading |
pubmed-meshheading:10691695-Acrylic Resins,
pubmed-meshheading:10691695-Anaphylaxis,
pubmed-meshheading:10691695-Animals,
pubmed-meshheading:10691695-Anti-Allergic Agents,
pubmed-meshheading:10691695-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:10691695-Ascitic Fluid,
pubmed-meshheading:10691695-Granuloma,
pubmed-meshheading:10691695-Humans,
pubmed-meshheading:10691695-Leukotriene B4,
pubmed-meshheading:10691695-Male,
pubmed-meshheading:10691695-Mice,
pubmed-meshheading:10691695-Neutrophils,
pubmed-meshheading:10691695-Pleuropneumonia,
pubmed-meshheading:10691695-Pneumonia,
pubmed-meshheading:10691695-Quinolines,
pubmed-meshheading:10691695-Rats,
pubmed-meshheading:10691695-Stereoisomerism,
pubmed-meshheading:10691695-Structure-Activity Relationship
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|
pubmed:year |
2000
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|
pubmed:articleTitle |
Heteroarylmethoxyphenylalkoxyiminoalkylcarboxylic acids as leukotriene biosynthesis inhibitors.
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|
pubmed:affiliation |
Immunoscience Research, Abbott Laboratories, D47K, AP10, 100 Abbott Park Road, Abbott Park, Illinois 600064, USA. teodozyj.kolasa@abbott.com
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pubmed:publicationType |
Journal Article,
In Vitro
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