| Literature DB >> 15261284 |
Matthew J Laufersweiler1, Todd A Brugel, Michael P Clark, Adam Golebiowski, Roger G Bookland, Steven K Laughlin, Mark P Sabat, Jennifer A Townes, John C VanRens, Biswanath De, Lily C Hsieh, Sandra A Heitmeyer, Karen Juergens, Kimberly K Brown, Marlene J Mekel, Richard L Walter, Michael J Janusz.
Abstract
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.Entities:
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Year: 2004 PMID： 15261284 DOI： 10.1016/j.bmcl.2004.06.001
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823