Rheumatoid Arthritis Research Today is a free monthly online journal that collates and summarizes the latest research about Rheumatoid Arthritis, including details on treatment, symptoms, causes, medication.

Inhibition of Tpl2 kinase and TNFalpha production with quinoline-3-carbonitriles for the treatment of rheumatoid arthritis.

Hu Y, Green N, Gavrin LK, Janz K, Kaila N, Li HQ, Thomason JR, Cuozzo JW, Hall JP, Hsu S, Nickerson-Nutter C, Telliez JB, Lin LL, Tam S

Department of Chemical and Screening Sciences, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA. fhu@wyeth.com <fhu@wyeth.com>

The synthesis and structure-activity studies of a series of quinoline-3-carbonitriles as inhibitors of Tpl2 kinase are described. Potent inhibitors of Tpl2 kinase with selectivity against a panel of selected kinases in enzymatic assays and specificity in cell-based phosphorylation assays in LPS-treated human monocytes were identified. Selected inhibitors with moderate activity in human whole blood assay effectively inhibited LPS/D-Gal induced TNFalpha release when administered intraperitoneally in mice.

Published 10 November 2006 in Bioorg Med Chem Lett, 16(23): 6067-72.
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