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

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

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29 Scopus citations

Abstract

A series of 1-substituted-3(5)-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl) pyrazoles 14a-d, 15a-d, 17a, 17b, 18a-d, 19a, and 19b has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 2-[3-(6-methylpyridin-2-yl)-4- (quinoxalin-6-yl)-1H-pyrazol-1-yl]-N-phenylethanethioamide (18a) inhibited ALK5 phosphorylation with an IC 50 value of 0.013 μM and showed 80% inhibition at 0.1 μM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.

Original languageEnglish
Pages (from-to)3917-3925
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume46
Issue number9
DOIs
StatePublished - Sep 2011

Bibliographical note

Funding Information:
This work was supported by RP-Grant 2009 of Ewha Womans University and 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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