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

  • Eur J Med Chem. 2011 Sep;46(9):3917-25. doi: 10.1016/j.ejmech.2011.05.063.
Cheng Hua Jin  1 ,  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
Affiliations
  • 1. College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, South Korea.
PMID: 21696866 DOI: 10.1016/j.ejmech.2011.05.063
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.

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