Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin- 2-yl)-5(4)-([1,2,4]triazolo[1,5-a]-pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Maddeboina Krishnaiah, Cheng Hua Jin, Domalapally Sreenu, Vura Bala Subrahmanyam, Kota Sudhakar Rao, Do Hyun Son, Hyun Ju Park, Seung Won Kim, Yhun Yhong Sheen, Dae Kee Kim

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17 Scopus citations

Abstract

A series of 2-benzylamino-4(5)-(6-methylpyridin-2-yl)-5(4)-([1,2,4] triazolo[1,5-a]pyridin-6-yl)thiazoles 12a-ab, 13a, 13b, and 18a-d has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The N-(3-fluorobenzyl)-4-(6- methylpyridin-2-yl)-5-([1,2,4]triazolo[1,5-a]pyridin-6-yl)thiazol-2-amine (12b) inhibited ALK5 phosphorylation with an IC50 value of 7.01 nM and showed 61% inhibition at 30 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.

Original languageEnglish
Pages (from-to)74-84
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume57
DOIs
StatePublished - Nov 2012

Bibliographical note

Funding Information:
This work was supported by a grant from Ministry of Education, Science and Technology, Korea ( 20100029596 ).

Keywords

  • ALK5 inhibitor
  • Cancer
  • Cell-based luciferase reporter assay
  • Docking
  • Fibrosis
  • Kinase assay
  • TGF-β

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