title: The development of new isoxazolone based inhibitors of tumor necrosis factor-alpha (TNF-alpha) production.
abstract: 4-Aryl-3-pyridyl and 4-aryl-3-pyrimidinyl based tumor necrosis factor-alpha (TNF-alpha) inhibitors, which contain a novel isoxazolone five-membered heterocyclic core are described. Many showed sub-micromolar activity against lipopolysaccharide-induced TNF-alpha production.
authors.affiliation: Health Care Research Center, Procter and Gamble Pharmaceuticals, 8700 Mason-Montgomery Road, Mason, OH 45040, USA.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Laughlin
authors.forename: Michael P
authors.initials: MP
authors.lastname: Clark
authors.forename: Jane F
authors.initials: JF
authors.lastname: Djung
authors.forename: Adam
authors.initials: A
authors.lastname: Golebiowski
authors.forename: Todd A
authors.initials: TA
authors.lastname: Brugel
authors.forename: Mark
authors.initials: M
authors.lastname: Sabat
authors.forename: Roger G
authors.initials: RG
authors.lastname: Bookland
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Laufersweiler
authors.forename: John C
authors.initials: JC
authors.lastname: VanRens
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Townes
authors.forename: Biswanath
authors.initials: B
authors.lastname: De
authors.forename: Lily C
authors.initials: LC
authors.lastname: Hsieh
authors.forename: Susan C
authors.initials: SC
authors.lastname: Xu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Walter
authors.forename: Marlene J
authors.initials: MJ
authors.lastname: Mekel
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Janusz
mesh_terms: D000079:Acetaldehyde; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D007555:Isoxazoles; D008070:Lipopolysaccharides; D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000079:Acetaldehyde