Synthesis and Biological Evaluation of 4(5)-(6-Alkylpyridin-2-yl)imidazoles as Transforming Growth Factor- Type 1 Rec
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- 作者：Dae-Kee Kim ; Yoojeung Jang ; Ho Soon Lee ; Hyun-Ju Park ; Jakyung Yoo
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：June 28, 2007
- 年：2007
- 卷：50
- 期：13
- 页码：3143 - 3147
- 全文大小：151K
- 年卷期：v.50,no.13(June 28, 2007)
- ISSN：1520-4804
文摘
A series of 4(5)-(6-alkylpyridin-2-yl)imidazoles 13a-p, 17a, and 17b have been synthesized and evaluatedfor ALK5 inhibitory activity in an enzyme assay and in cell-based luciferase reporter assays. The quinoxalinylanalogue 13e inhibited ALK5 phosphorylation with an IC50 of 0.012 
M and showed more than 90% inhibitionat 0.05 M in a luciferase reporter assay using HaCaT cells transiently transfected with p3TP-luc reporterconstruct. The binding mode of 13e generated by flexible docking studies shows that 13e fits well into theactive site cavity of ALK5 by forming several tight interactions.
M and showed more than 90% inhibitionat 0.05 M in a luciferase reporter assay using HaCaT cells transiently transfected with p3TP-luc reporterconstruct. The binding mode of 13e generated by flexible docking studies shows that 13e fits well into theactive site cavity of ALK5 by forming several tight interactions.