Synthesis and biological evaluation of 4(5)-(6-alkylpyridin-2-yl)imidazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Dae Kee Kim; Yoojeung Jang; Soon Lee Ho; Hyun Ju Park; Jakyung Yoo

doi:10.1021/jm070129k

Synthesis and biological evaluation of 4(5)-(6-alkylpyridin-2-yl)imidazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Dae Kee Kim, Yoojeung Jang, Soon Lee Ho, Hyun Ju Park, Jakyung Yoo

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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
Pages (from-to)	3143-3147
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	50
Issue number	13
DOIs	https://doi.org/10.1021/jm070129k
State	Published - 28 Jun 2007

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title = "Synthesis and biological evaluation of 4(5)-(6-alkylpyridin-2-yl)imidazoles as transforming growth factor-β type 1 receptor kinase inhibitors",

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.",

author = "Kim, {Dae Kee} and Yoojeung Jang and Ho, {Soon Lee} and Park, {Hyun Ju} and Jakyung Yoo",

year = "2007",

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T1 - Synthesis and biological evaluation of 4(5)-(6-alkylpyridin-2-yl)imidazoles as transforming growth factor-β type 1 receptor kinase inhibitors

AU - Kim, Dae Kee

AU - Jang, Yoojeung

AU - Ho, Soon Lee

AU - Park, Hyun Ju

AU - Yoo, Jakyung

PY - 2007/6/28

Y1 - 2007/6/28

N2 - 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.

AB - 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.

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ER -

Synthesis and biological evaluation of 4(5)-(6-alkylpyridin-2-yl)imidazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Abstract

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