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

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...

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Autores principales: Park, Myoung-Soon, Park, Hyun-Ju, An, Young Jae, Choi, Joon Hun, Cha, Geunyoung, Lee, Hwa Jeong, Park, So-Jung, Dewang, Purushottam M., Kim, Dae-Kee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144182/
https://www.ncbi.nlm.nih.gov/pubmed/32164459
http://dx.doi.org/10.1080/14756366.2020.1734799
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author Park, Myoung-Soon
Park, Hyun-Ju
An, Young Jae
Choi, Joon Hun
Cha, Geunyoung
Lee, Hwa Jeong
Park, So-Jung
Dewang, Purushottam M.
Kim, Dae-Kee
author_facet Park, Myoung-Soon
Park, Hyun-Ju
An, Young Jae
Choi, Joon Hun
Cha, Geunyoung
Lee, Hwa Jeong
Park, So-Jung
Dewang, Purushottam M.
Kim, Dae-Kee
author_sort Park, Myoung-Soon
collection PubMed
description 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-CONH(2) 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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spelling pubmed-71441822020-04-13 Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors Park, Myoung-Soon Park, Hyun-Ju An, Young Jae Choi, Joon Hun Cha, Geunyoung Lee, Hwa Jeong Park, So-Jung Dewang, Purushottam M. Kim, Dae-Kee J Enzyme Inhib Med Chem Research Paper 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-CONH(2) 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. Taylor & Francis 2020-03-12 /pmc/articles/PMC7144182/ /pubmed/32164459 http://dx.doi.org/10.1080/14756366.2020.1734799 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Park, Myoung-Soon
Park, Hyun-Ju
An, Young Jae
Choi, Joon Hun
Cha, Geunyoung
Lee, Hwa Jeong
Park, So-Jung
Dewang, Purushottam M.
Kim, Dae-Kee
Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors
title Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors
title_full Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors
title_fullStr Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors
title_full_unstemmed Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors
title_short Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors
title_sort synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1h-imidazoles as alk5 inhibitors
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144182/
https://www.ncbi.nlm.nih.gov/pubmed/32164459
http://dx.doi.org/10.1080/14756366.2020.1734799
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