2-Phenyl and 2-heterocyclic-4-(3-(pyridin-2-yl)-1H-pyrazol-4-yl)pyridines as inhibitors of TGF-β1 and activin A signalling

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5642-5. doi: 10.1016/j.bmcl.2010.12.120. Epub 2010 Dec 30.

Abstract

Novel inhibitors of TGF-β1 and activin A signalling based on a 2-aryl-4-(3-(pyridin-2-yl)-1H-pyrazol-4-yl)pyridine pharmacophore have been synthesised. Compounds containing phenyl or aromatic nitrogen heterocycle substituents inhibited both types of signalling with HEK-293T cells in culture, with a selectivity preference for TGF-β1. Synthetic compounds containing pyridin-3-yl, pyrazol-4-yl, pyrazol-1-yl or 1H-imidazoyl-1-yl substituents exhibited structural and functional attributes suitable for further investigation related to the development of more potent TGF-β inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / antagonists & inhibitors*
  • Activins / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology*
  • Humans
  • Molecular Structure
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Signal Transduction / drug effects
  • Stereoisomerism
  • Structure-Activity Relationship
  • Transforming Growth Factor beta1 / antagonists & inhibitors*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Heterocyclic Compounds
  • Pyridines
  • Transforming Growth Factor beta1
  • activin A
  • Activins