1093952-95-4Relevant academic research and scientific papers
Synthesis and biological evaluation of 4(5)-(6-methylpyridin-2-yl)imidazoles and -pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors
Kim, Dae-Kee,Lee, Yeon-Im,Lee, Yeon Woo,Dewang, Purushottam M.,Sheen, Yhun Yhong,Kim, Yeo Woon,Park, Hyun-Ju,Yoo, Jakyung,Lee, Ho Soon,Kim, Yong-Kook
experimental part, p. 4459 - 4467 (2010/08/22)
A series of 4(5)-(6-methylpyridin-2-yl)imidazoles 16-19 and -pyrazoles 22-29, 33, and 34 have been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in cell-based luciferase reporter assays. The 6-quinolinyl imidazole analogs 16 and 18 inhibited ALK5 phosphorylation with IC50 values of 0.026 and 0.034 μM, respectively. In a luciferase reporter assay using HaCaT cells transiently transfected with p3TP-luc reporter construct, 18 displayed 66% inhibition at 0.05 μM, while competitor compounds 2 and 3 showed 44% inhibition. The binding mode of 18 generated by flexible docking studies with ALK5:18 complex shows that it fits well into the active site cavity of ALK5 by forming broad and tight interactions.
