Imidazo[1,2-a]pyridine derivatives as inhibitors of TNF-α 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-α promoter activity in T cells. The methyl ester 3b is the most potent, inhibiting the TNF-α driven reporter gene expression in Jurkat T cells with an IC50-value of 2.0 μg/ml (3.6 μM). In addition, compound 3b inhibited the inducible TNF-α production in the myelomonocytic U937 cells with an IC50-value of 4.6 μM.

A set of imidazo[1,2-a]pyridine derivatives prepared from the fungal metabolite podoscyphic acid have been evaluated for their ability to inhibit the inducible TNF-α promoter activity in T cells.Figure optionsDownload as PowerPoint slide