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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2002-5-28
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pubmed:abstractText |
Structure-activity relationship studies directed toward improving the potency and metabolic stability of CDP-840 (3) resulted in the discovery of L-791,943 (11n) as a potent (HWB TNF-alpha = 0.67 microM) and orally active phosphodiesterase type 4 (PDE4) inhibitor. This compound, which bears a stable bis-difluoromethoxy catechol and a pendant hexafluorocarbinol, exhibited a long half-life in rat and in squirrel monkey. It is well tolerated in ferret with an emetic threshold greater than 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig and in the ascaris-induced bronchoconstriction models in sheep and squirrel monkey.
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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 |
0960-894X
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pubmed:author |
pubmed-author:BlouinMarcM,
pubmed-author:BrideauChristineC,
pubmed-author:ChanChi ChungCC,
pubmed-author:ChauretNathalieN,
pubmed-author:DucharmeYvesY,
pubmed-author:GirardMarioM,
pubmed-author:GirardYvesY,
pubmed-author:GuayDanielD,
pubmed-author:HamelPierreP,
pubmed-author:HuangZhengZ,
pubmed-author:JonesTom RTR,
pubmed-author:LalibertéFranceF,
pubmed-author:MassonPaulP,
pubmed-author:McAuliffeMaliaM,
pubmed-author:PiechutaHannaH,
pubmed-author:SilvaJoséJ,
pubmed-author:YoungRobert NRN
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1457-61
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12031319-3',5'-Cyclic-AMP Phosphodiesterases,
pubmed-meshheading:12031319-Administration, Oral,
pubmed-meshheading:12031319-Animals,
pubmed-meshheading:12031319-Bronchoconstriction,
pubmed-meshheading:12031319-Cell Line, Transformed,
pubmed-meshheading:12031319-Cyclic Nucleotide Phosphodiesterases, Type 4,
pubmed-meshheading:12031319-Emetics,
pubmed-meshheading:12031319-Ferrets,
pubmed-meshheading:12031319-Guinea Pigs,
pubmed-meshheading:12031319-Half-Life,
pubmed-meshheading:12031319-Humans,
pubmed-meshheading:12031319-Inhibitory Concentration 50,
pubmed-meshheading:12031319-Ovalbumin,
pubmed-meshheading:12031319-Phosphodiesterase Inhibitors,
pubmed-meshheading:12031319-Pyridines,
pubmed-meshheading:12031319-Rats,
pubmed-meshheading:12031319-Recombinant Fusion Proteins,
pubmed-meshheading:12031319-Saimiri,
pubmed-meshheading:12031319-Sheep,
pubmed-meshheading:12031319-Structure-Activity Relationship,
pubmed-meshheading:12031319-Tumor Necrosis Factor-alpha
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pubmed:year |
2002
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pubmed:articleTitle |
Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.
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pubmed:affiliation |
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe-Claire-Dorval, Québec, Canada H9R 4P8. daniel_guay@merck.com
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pubmed:publicationType |
Journal Article,
Comparative Study
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