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

Ewha Womans University
Sungkyunkwan University

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

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

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

Access to Document

10.1080/14756366.2020.1734799

Cite this

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

@article{0720a97710244997a726cef6ccfa87d8,

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

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.",

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

author = "Park, \{Myoung Soon\} and Park, \{Hyun Ju\} and An, \{Young Jae\} and Choi, \{Joon Hun\} and Geunyoung Cha and Lee, \{Hwa Jeong\} and Park, \{So Jung\} and Dewang, \{Purushottam M.\} and Kim, \{Dae Kee\}",

note = "Publisher Copyright: {\textcopyright} 2020, {\textcopyright} 2020 The Author(s). Published by Informa UK Limited, trading as Taylor \& Francis Group.",

year = "2020",

month = jan,

day = "1",

doi = "10.1080/14756366.2020.1734799",

language = "English",

volume = "35",

pages = "702--712",

journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",

issn = "1475-6366",

publisher = "Taylor and Francis Ltd.",

number = "1",

}

TY - JOUR

T1 - Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors

AU - Park, Myoung Soon

AU - Park, Hyun Ju

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

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

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

KW - ALK5 inhibition

KW - cancer immunotherapeutic agent

KW - docking

UR - https://www.scopus.com/pages/publications/85081741075

U2 - 10.1080/14756366.2020.1734799

DO - 10.1080/14756366.2020.1734799

M3 - Article

C2 - 32164459

AN - SCOPUS:85081741075

SN - 1475-6366

VL - 35

SP - 702

EP - 712

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

IS - 1

ER -

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

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this