The development of novel inhibitors of tumor necrosis factor-alpha production based on substituted [5,5]-bicyclic pyrozolones

Novel substituted [5,5]-bicyclic pyrzazolones are presented as inhibitors of tumor necrosis factor-{alpha} (TNF-{alpha}) production. Many of these compounds show low nanomolar activity against lipopolysaccaride (LPS)-induced TNF-{alpha} production in THP-1 cells. This class of molecules was co-cryst...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry Vol. 14; no. (16) ; 2004
Main Authors: Laufersweiler, Matthew, Brugel, Todd, Clark, Michael, Golebiowski, Adam, Bookland, Roger, Laughlin, Steven, Sabat, Mark, Townes, Jennifer, VanRens, John, De, Biswanath, Hsieh, Lily, Heitmeyer, Sandra, Juergens, Karen, Brown, Kimberly, Mekel, Marlene, Walter, Richard, Janusz, Michael
Format: Journal Article
Language:English
Published: United States 16-11-2010
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Summary:Novel substituted [5,5]-bicyclic pyrzazolones are presented as inhibitors of tumor necrosis factor-{alpha} (TNF-{alpha}) production. Many of these compounds show low nanomolar activity against lipopolysaccaride (LPS)-induced TNF-{alpha} production in THP-1 cells. This class of molecules was co-crystallized with mutated p38, and several analogs showed good oral bioavailability in the rat. Oral activity of these compounds in the rat iodoacetate model for osteoarthritis is discussed.
Bibliography:USDOE
ISSN:0968-0896
1464-3391