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

Journal Article · · Bioorgan. Med. Chem.
OSTI ID:1008722
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.
Research Organization:
Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
Sponsoring Organization:
USDOE
OSTI ID:
1008722
Journal Information:
Bioorgan. Med. Chem., Journal Name: Bioorgan. Med. Chem. Journal Issue: (16) ; 2004 Vol. 14; ISSN BMECEP; ISSN 0968-0896
Country of Publication:
United States
Language:
ENGLISH

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