Imidazo[1,2-a]pyridine derivatives as inhibitors of TNF-alpha expression in T cells.
Novel hexahydroimidazo[1,2-a]pyridines prepared by the addition of ethyl (1-benzylimidazolidin-2-ylidene)acetate (2) to the fungal metabolite podoscyphic acid (1a) and esters of 1a have been evaluated for their ability to inhibit the inducible TNF-alpha promoter activity in T cells. The methyl ester 3b is the most potent, inhibiting the TNF-alpha driven reporter gene expression in Jurkat T cells with an IC(50)-value of 2.0 microg/ml (3.6 microM). In addition, compound 3b inhibited the inducible TNF-alpha production in the myelomonocytic U937 cells with an IC(50)-value of 4.6 microM.
Institut für Biotechnologie und Wirkstoff-Forschung e. V., Erwin-Schrödinger-Str. 56, D-67663 Kaiserslautern, Germany.
Jan
J
Rether
Gerhard
G
Erkel
Timm
T
Anke
Johan
J
Bajtner
Olov
O
Sterner
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D011401:Promoter Regions, Genetic / Q000235:genetics; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C001439:imidazo(1,2-a)pyridine