Abstract
A series of 4(5)-(6-alkylpyridin-2-yl)imidazoles 13a-p, 17a, and 17b have been synthesized and evaluated for ALK5 inhibitory activity in an enzyme assay and in cell-based luciferase reporter assays. The quinoxalinyl analogue 13e inhibited ALK5 phosphorylation with an IC50 of 0.012 μM and showed more than 90% inhibition at 0.05 μM in a luciferase reporter assay using HaCaT cells transiently transfected with p3TP-luc reporter construct. The binding mode of 13e generated by flexible docking studies shows that 13e fits well into the active site cavity of ALK5 by forming several tight interactions.
Original language | English |
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Pages (from-to) | 3143-3147 |
Number of pages | 5 |
Journal | Journal of Medicinal Chemistry |
Volume | 50 |
Issue number | 13 |
DOIs | |
State | Published - 28 Jun 2007 |