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

  • J Med Chem. 2007 Jun 28;50(13):3143-7. doi: 10.1021/jm070129k.
Dae-Kee Kim  1 ,  Yoojeung Jang ,  Ho Soon Lee ,  Hyun-Ju Park ,  Jakyung Yoo
Affiliations
  • 1. College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Korea. [email protected]
PMID: 17552507 DOI: 10.1021/jm070129k
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 muM and showed more than 90% inhibition at 0.05 muM 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.