1.
Bioorg Med Chem Lett
; 14(10): 2411-5, 2004 May 17.
Article
in English
| MEDLINE
| ID: mdl-15109623
ABSTRACT
The discovery and structure-activity relationship of a novel series of coumarin-based TNF-alpha inhibitors is described. Starting from the initial lead 1a, various derivatives were prepared surrounding the coumarin core structure to optimize the in vitro inhibitory activity of TNF-alpha production by human peripheral blood mononuclear cells (hPBMC), stimulated by bacterial lipopolysaccharide (LPS). Selected compounds also demonstrated in vivo inhibition of TNF-alpha production in rats.
Subject(s)
Coumarins/chemical synthesis , Coumarins/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Cells, Cultured , Dose-Response Relationship, Drug , Humans , Inhibitory Concentration 50 , Leukocytes, Mononuclear/metabolism , Lipopolysaccharides/pharmacology , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/metabolism
2.
