Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors

Myoung Soon Park; Hyun Ju Park; Young Jae An; Joon Hun Choi; Geunyoung Cha; Hwa Jeong Lee; So Jung Park; Purushottam M. Dewang; Dae Kee Kim

doi:10.1080/14756366.2020.1734799

Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors

Myoung Soon Park, Hyun Ju Park, Young Jae An, Joon Hun Choi, Geunyoung Cha, Hwa Jeong Lee, So Jung Park, Purushottam M. Dewang, Dae Kee Kim

Department of Pharmacy

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

8 Scopus citations

Abstract

A series of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles, 7a–c, 11a–h, and 16a–h has been synthesised and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Incorporation of a quinoxalin-6-yl moiety and a methylene linker at the 4- and 2-position of the imidazole ring, respectively, and a m-CONH₂ substituent in the phenyl ring generated a highly potent and selective ALK5 inhibitor 11e. Docking model of ALK5 in complex with 11e showed that it fitted well in the ATP-binding pocket with favourable interactions.

Original language	English
Pages (from-to)	702-712
Number of pages	11
Journal	Journal of Enzyme Inhibition and Medicinal Chemistry
Volume	35
Issue number	1
DOIs	https://doi.org/10.1080/14756366.2020.1734799
State	Published - 1 Jan 2020

Keywords

2,4-Disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles
ALK5 inhibition
cancer immunotherapeutic agent
docking

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Park, M. S., Park, H. J., An, Y. J., Choi, J. H., Cha, G., Lee, H. J., Park, S. J., Dewang, P. M., & Kim, D. K. (2020). Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 35(1), 702-712. https://doi.org/10.1080/14756366.2020.1734799

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abstract = "A series of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles, 7a–c, 11a–h, and 16a–h has been synthesised and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Incorporation of a quinoxalin-6-yl moiety and a methylene linker at the 4- and 2-position of the imidazole ring, respectively, and a m-CONH2 substituent in the phenyl ring generated a highly potent and selective ALK5 inhibitor 11e. Docking model of ALK5 in complex with 11e showed that it fitted well in the ATP-binding pocket with favourable interactions.",

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doi = "10.1080/14756366.2020.1734799",

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AU - An, Young Jae

AU - Choi, Joon Hun

AU - Cha, Geunyoung

AU - Lee, Hwa Jeong

AU - Park, So Jung

AU - Dewang, Purushottam M.

AU - Kim, Dae Kee

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AB - A series of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles, 7a–c, 11a–h, and 16a–h has been synthesised and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Incorporation of a quinoxalin-6-yl moiety and a methylene linker at the 4- and 2-position of the imidazole ring, respectively, and a m-CONH2 substituent in the phenyl ring generated a highly potent and selective ALK5 inhibitor 11e. Docking model of ALK5 in complex with 11e showed that it fitted well in the ATP-binding pocket with favourable interactions.

KW - 2,4-Disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles

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KW - cancer immunotherapeutic agent

KW - docking

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Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors

Abstract

Keywords

UN SDGs

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