Diversity-Oriented Synthesis of Imidazo-Dipyridines with Anticancer Activity via the Groebke-Blackburn-Bienaymé and TBAB-Mediated Cascade Reaction in One Pot

J Org Chem. 2019 Oct 4;84(19):12632-12638. doi: 10.1021/acs.joc.9b01385. Epub 2019 Aug 12.

Abstract

A facile and metal-free one-pot protocol for the synthesis of fused imidazopyridine scaffolds has been developed. This novel protocol combines the Groebke-Blackburn-Bienaymé reaction (GBBR) with a sequential TBAB-mediated cyclization cascade. Biological evaluation demonstrated that compound 6a inhibits human prostate cancer cell DU-145 proliferation with an IC50 of 1.6 μM. The molecular mechanism study indicates that 6a significantly suppresses the oncogenic Erk kinase phosphorylation at 3 μM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Cyclization
  • Drug Screening Assays, Antitumor
  • Humans
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Microwaves
  • Models, Molecular
  • Molecular Structure
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Quaternary Ammonium Compounds / chemistry
  • Quaternary Ammonium Compounds / pharmacology*

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Pyridines
  • Quaternary Ammonium Compounds
  • tetrabutylammonium