One-pot regioselective synthesis of tetrahydroindazolones and evaluation of their antiproliferative and Src kinase inhibitory activities

Bioorg Med Chem Lett. 2012 Jan 1;22(1):410-4. doi: 10.1016/j.bmcl.2011.10.124. Epub 2011 Nov 7.

Abstract

A number of 2-substituted tetrahydroindazolones were synthesized by three-component condensation reaction of 1,3-diketones, substituted hydrazines, benzaldehydes, and Yb(OTf)(3) as a catalyst in [bmim][BF(4)] ionic liquid using a simple, efficient, and economical one-pot method. The synthesized tetrahydroindazolones were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. 3,4-Dichlorophenyl tetrahydroindazolone derivative (15) inhibited the cell proliferation of HT-29 and SK-OV-3 cells by 62% and 58%, respectively. 2,3-Diphenylsubstituted tetrahydroindazolone derivatives, inhibited the cell proliferation of HT-29 cells by 65-72% at a concentration of 50 μM. In general, the tetrahydroindazolones showed modest inhibition of c-Src kinase where 4-tertbutylphenyl- and 3,4-dichlorophenyl- derivatives showed the inhibition of c-Src kinase with IC(50) values of 35.1 and 50.7 μM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Cell Proliferation / drug effects
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • HT29 Cells
  • Humans
  • Indazoles / pharmacology*
  • Inhibitory Concentration 50
  • Ions
  • Magnetic Resonance Spectroscopy / methods
  • Models, Chemical
  • Models, Molecular
  • Molecular Conformation
  • Structure-Activity Relationship
  • src-Family Kinases / chemistry*

Substances

  • Indazoles
  • Ions
  • src-Family Kinases