Design and synthesis of 2,6-disubstituted-8-amino imidazo[1,2a]pyridines, a promising privileged structure

Bioorg Med Chem. 2018 Jul 23;26(12):3296-3307. doi: 10.1016/j.bmc.2018.04.057. Epub 2018 Apr 30.

Abstract

Imidazo[1,2a]pyridines have gained much interest in the field of medicinal chemistry research. In the aim of accessing new privileged structure, we decided to design and synthesize 8-aminated-imidazo[1,2a]pyridines substituted on positions 2 and 6. This scaffold, rarely found in the literature, was obtained via palladium-catalyzed coupling reactions (Suzuki reaction or N-hydroxysuccinimidyl activated ester method) and tested on adenosine receptor A2A. We demonstrated how incorporation of an exocyclic amine enhanced affinity towards this receptor while maintaining low cytotoxicity.

Keywords: A(2A) receptor; Amino-imidazopyridine; Palladium-catalyzed coupling reaction; Privileged structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A2 Receptor Antagonists / chemical synthesis
  • Adenosine A2 Receptor Antagonists / metabolism
  • Adenosine A2 Receptor Antagonists / pharmacology
  • Binding Sites
  • Catalysis
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Design*
  • HEK293 Cells
  • Humans
  • Molecular Docking Simulation
  • Palladium / chemistry
  • Protein Structure, Tertiary
  • Pyridines / chemistry*
  • Pyridines / metabolism
  • Pyridines / pharmacology
  • Receptor, Adenosine A2A / chemistry
  • Receptor, Adenosine A2A / metabolism
  • Structure-Activity Relationship

Substances

  • Adenosine A2 Receptor Antagonists
  • Pyridines
  • Receptor, Adenosine A2A
  • Palladium
  • imidazo(1,2-a)pyridine