Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine and 1H-pyrazolo[3,4-b]pyridine derivatives as c-Met inhibitors

Bioorg Chem. 2016 Apr;65:146-58. doi: 10.1016/j.bioorg.2016.02.009. Epub 2016 Mar 2.


Five novel 1H-pyrrolo[2,3-b]pyridine or 1H-pyrazolo[3,4-b]pyridine derivatives, with a methylene, sulfur, sulfoxide or cyclopropyl group as a linker, were designed, synthesized and biologically evaluated against c-Met and ALK. The development of these methods of compound synthesis may provide an important reference for the construction of novel 7-azaindole and 7-azaindazole derivatives with a single atom linker. The enzyme assay and cell assay in vitro showed that compound 9 displayed strong c-Met kinase inhibition with IC50 of 22.8nM, moderate ALK kinase inhibition, and strong cell inhibition with MKN-45 IC50 of 329nM and EBC-1 IC50 of 479nM. In order to find the better candidate compounds, compounds 8, 9 and 10 have been selected as tool compounds for further optimization.

Keywords: Azaindazole; Azaindole; Biological evaluation; Synthesis; c-Met inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / metabolism
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / pharmacology*
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Structure-Activity Relationship


  • 1H-pyrazolo(3,4-b)pyridine
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Pyrroles
  • Proto-Oncogene Proteins c-met
  • pyrrolo(2, 3-b)pyridine