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Bioorg Med Chem Lett. 2006 Dec 1;16(23):6067-72. Epub 2006 Sep 14.

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

Author information

1
Department of Chemical and Screening Sciences, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA. fhu@wyeth.com <fhu@wyeth.com>

Abstract

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.

PMID:
16973359
DOI:
10.1016/j.bmcl.2006.08.102
[Indexed for MEDLINE]

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