Synthesis and biological evaluation of 1-substituted-3-(6-methylpyridin-2- yl)-4-([1,2,4triazolo[1,5-apyridin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Cheng Hua Jin, Maddeboina Krishnaiah, Domalapally Sreenu, Vura Bala Subrahmanyam, Kota Sudhakar Rao, Annaji Venkata Nagendra Mohan, Chul Yong Park, Jee Yeon Son, Yhun Yhong Sheen, Dae Kee Kim

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4triazolo[1,5- apyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4triazolo[1,5-apyridin-6-yl)- N-(4-methoxyphenyl)-3-(6-methylpyridin-2-yl)-1H-pyrazole-1-carbothioamide (14n) inhibited ALK5 phosphorylation with IC 50 value of 0.57 nM and showed 94% inhibition at 100 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.

Original languageEnglish
Pages (from-to)6049-6053
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number20
DOIs
StatePublished - 15 Oct 2011

Keywords

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

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