The development of new isoxazolone based inhibitors of tumor necrosis factor-alpha (TNF-alpha) production.
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.
Laughlin
Steven K
SK
Health Care Research Center, Procter and Gamble Pharmaceuticals, 8700 Mason-Montgomery Road, Mason, OH 45040, USA.
Clark
Michael P
MP
Djung
Jane F
JF
Golebiowski
Adam
A
Brugel
Todd A
TA
Sabat
Mark
M
Bookland
Roger G
RG
Laufersweiler
Matthew J
MJ
VanRens
John C
JC
Townes
Jennifer A
JA
De
Biswanath
B
Hsieh
Lily C
LC
Xu
Susan C
SC
Walter
Richard L
RL
Mekel
Marlene J
MJ
Janusz
Michael J
MJ
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
D007555:Isoxazoles; D008070:Lipopolysaccharides; D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000079:Acetaldehyde