Investigation of the effect of varying the 4-anilino and 7-alkoxy groups of 3-quinolinecarbonitriles on the inhibition of Src kinase activity

Bioorg Med Chem Lett. 2003 Nov 3;13(21):3797-800. doi: 10.1016/j.bmcl.2003.07.001.

Abstract

Several 7-alkoxy-4-anilino-3-quinolinecarbonitriles were synthesized and evaluated for Src kinase inhibitory activity. Optimal inhibition of both Src enzymatic and cellular activity was seen with analogues having a 2,4-dichloro-5-methoxyaniline group at C-4. Compound 18, which has a 1-methylpiperidinemethoxy group at C-7, showed in vivo activity in a xenograft model.

MeSH terms

  • Animals
  • Cell Line
  • Cell Transplantation
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Fibroblasts / enzymology
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Mice
  • Mice, Nude
  • Nitriles / chemical synthesis*
  • Nitriles / pharmacology*
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology*
  • Rats
  • Structure-Activity Relationship
  • Transplantation, Heterologous
  • src-Family Kinases / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Indicators and Reagents
  • Nitriles
  • Quinolines
  • src-Family Kinases