Design and synthesis of triazolopyridazines substituted with methylisoquinolinone as selective c-Met kinase inhibitors

Bioorg Med Chem Lett. 2011 Dec 1;21(23):7185-8. doi: 10.1016/j.bmcl.2011.09.066. Epub 2011 Sep 22.

Abstract

A series of triazolopyridazines substituted with methylisoquinolinone were designed and synthesized. Some of the triazolopyridazines strongly inhibited c-Met kinase and showed good anti-proliferative activity against a panel of c-Met-amplified gastric cancer cell lines (MKN-45, SNU-5 and Hs746T).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Design*
  • Enzyme Activation / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors* / chemical synthesis
  • Protein Kinase Inhibitors* / chemistry
  • Protein Kinase Inhibitors* / pharmacology
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Pyridazines / chemical synthesis*
  • Pyridazines / chemistry
  • Pyridazines / pharmacology
  • Rats
  • Stomach Neoplasms / drug therapy*
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology

Substances

  • Isoquinolines
  • Protein Kinase Inhibitors
  • Pyridazines
  • Triazoles
  • Proto-Oncogene Proteins c-met