A series of 1-substituted-3(5)-(6-methylpyridin-2-yl)-4-(quinolin-6-yl) pyrazoles 14a-e, 15a-e, 17a-c, and 18a-d have been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 6-quinolinyl pyrazole analogue 14b inhibited ALK5 phosphorylation with IC50 value of 0.022 μM and showed 84% inhibition at 0.1 μM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.
- ALK5 inhibitor
- Cell-based luciferase reporter assay
- Kinase assay