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

Research output: Contribution to journalArticlepeer-review

5 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 languageEnglish
Pages (from-to)702-712
Number of pages11
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume35
Issue number1
DOIs
StatePublished - 1 Jan 2020

Bibliographical note

Funding Information:
This work was supported by the Ministry of Commerce, Industry and Energy, Korea under grant [numbers M1-0310-43-0001 and M1-0310-43-0002].

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

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