A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4triazolo[1,5- apyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4triazolo[1,5-apyridin-6-yl)- N-(4-methoxyphenyl)-3-(6-methylpyridin-2-yl)-1H-pyrazole-1-carbothioamide (14n) inhibited ALK5 phosphorylation with IC 50 value of 0.57 nM and showed 94% inhibition at 100 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.
- ALK5 inhibitor
- Cell-based luciferase reporter assay
- Kinase assay