Author/Authors :
Yonghan Hu، نويسنده , , Neal Green، نويسنده , , Lori K. Gavrin، نويسنده , , Kristin Janz، نويسنده , , Neelu Kaila، نويسنده , , Huan-Qiu Li، نويسنده , , Jennifer R. Thomason، نويسنده , , John W. Cuozzo، نويسنده , , J. Perry Hall، نويسنده , , Sang Hsu، نويسنده , , Cheryl Nickerson-Nutter، نويسنده , , Jean-Baptiste Telliez، نويسنده , , Lih-Ling Lin، نويسنده , , Steve Tam، نويسنده ,
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 TNFα release when administered intraperitoneally in mice.
