Discovery of indazoles as inhibitors of Tpl2 kinase

Synthesis, modeling and structure–activity relationship of indazoles as inhibitors of Tpl2 kinase are described. From a high throughput screening effort, we identified an indazole hit compound 5 that has a single digit micromolar Tpl2 activity. Through SAR modifications at the C3 and C5 positions of the indazole, we discovered compound 31 with good potency in LANCE assay and cell-based p-Erk assay.

Graphical abstractSynthesis, modeling and structure–activity relationship of indazoles as inhibitors of Tpl2 kinase are described. Through SAR modifications at the C3 and C5 positions of the indazole, we discovered compound 31 with good potency in LANCE assay (0.047 μM) and cell-based p-Erk assay (0.079 μM).Figure optionsDownload full-size imageDownload as PowerPoint slide