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 Pharmaceutical Sciences

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

9 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

Bibliographical note

Publisher Copyright:
© 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

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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AU - Cha, Geunyoung

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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

Bibliographical note

Keywords

UN SDGs

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