The development of new isoxazolone based inhibitors of tumor necrosis factor-alpha (TNF-alpha) production

Steven K Laughlin; Michael P Clark; Jane F Djung; Adam Golebiowski; Todd A Brugel; Mark Sabat; Roger G Bookland; Matthew J Laufersweiler; John C VanRens; Jennifer A Townes; Biswanath De; Lily C Hsieh; Susan C Xu; Richard L Walter; Marlene J Mekel; Michael J Janusz

doi:10.1016/j.bmcl.2005.02.066

The development of new isoxazolone based inhibitors of tumor necrosis factor-alpha (TNF-alpha) production

Bioorg Med Chem Lett. 2005 May 2;15(9):2399-403. doi: 10.1016/j.bmcl.2005.02.066.

Authors

Steven K Laughlin¹, Michael P Clark, Jane F Djung, Adam Golebiowski, Todd A Brugel, Mark Sabat, Roger G Bookland, Matthew J Laufersweiler, John C VanRens, Jennifer A Townes, Biswanath De, Lily C Hsieh, Susan C Xu, Richard L Walter, Marlene J Mekel, Michael J Janusz

Affiliation

¹ Health Care Research Center, Procter and Gamble Pharmaceuticals, 8700 Mason-Montgomery Road, Mason, OH 45040, USA.

PMID: 15837333
DOI: 10.1016/j.bmcl.2005.02.066

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.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Acetaldehyde
Binding Sites
Cell Line
Humans
Isoxazoles / chemical synthesis*
Isoxazoles / pharmacology*
Lipopolysaccharides / pharmacology
Models, Molecular
Molecular Structure
Protein Conformation
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology
Structure-Activity Relationship
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Tumor Necrosis Factor-alpha / chemistry
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors

Substances

Isoxazoles
Lipopolysaccharides
Pyrimidines
Tumor Necrosis Factor-alpha
p38 Mitogen-Activated Protein Kinases
Acetaldehyde