Imidazo[1,2-a]pyridine derivatives as inhibitors of TNF-alpha expression in T cells

Summary, in English

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.

• Author: Jan Rether; Gerhard Erkel; Timm Anke; Johan Eriksson Bajtner; Olov Sterner
• Department/s: Centre for Analysis and Synthesis
• Publishing year: 2008
• Language: English
• Pages: 1236-1241
• Publication/Series: Bioorganic & Medicinal Chemistry
• Volume: 16
• Issue: 3
• Links: http://dx.doi.org/10.1016/j.bmc.2007.10.074
• Document type: Journal article
• Publisher: Elsevier
• Topic: Organic Chemistry
• Keywords: Semisynthesis; Podoscyphic acid; Inflammation; Promoter activity; TNF-α; Inhibitor
• Status: Published
• ISBN/ISSN/Other: ISSN: 0968-0896