Synthesis and biological evaluation of 4(5)-(6-alkylpyridin-2-yl)imidazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Dae Kee Kim, Yoojeung Jang, Soon Lee Ho, Hyun Ju Park, Jakyung Yoo

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

A series of 4(5)-(6-alkylpyridin-2-yl)imidazoles 13a-p, 17a, and 17b have been synthesized and evaluated for ALK5 inhibitory activity in an enzyme assay and in cell-based luciferase reporter assays. The quinoxalinyl analogue 13e inhibited ALK5 phosphorylation with an IC50 of 0.012 μM and showed more than 90% inhibition at 0.05 μM in a luciferase reporter assay using HaCaT cells transiently transfected with p3TP-luc reporter construct. The binding mode of 13e generated by flexible docking studies shows that 13e fits well into the active site cavity of ALK5 by forming several tight interactions.

Original languageEnglish
Pages (from-to)3143-3147
Number of pages5
JournalJournal of Medicinal Chemistry
Volume50
Issue number13
DOIs
StatePublished - 28 Jun 2007

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