8-Fluoroimidazo[1,2-a]pyridine: synthesis, physicochemical properties and evaluation as a bioisosteric replacement for imidazo[1,2-a]pyrimidine in an allosteric modulator ligand of the GABA A receptor

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1518-22. doi: 10.1016/j.bmcl.2005.12.037. Epub 2006 Jan 4.

Abstract

8-Fluoroimidazo[1,2-a]pyridine has been established as a physicochemical mimic of imidazo[1,2-a]pyrimidine, using both in silico and traditional techniques. Furthermore, a novel synthesis of a 3,7-disubstituted-8-fluoroimidazopyridine 3 has been developed and the utility of the physicochemical mimicry has been demonstrated in an in vitro system. Here, the 8-fluoroimidazopyridine ring contained in ligand 3 acts as a bioisosteric replacement for imidazopyrimidine in the GABA(A) receptor modulator 2.

Publication types

  • Evaluation Study

MeSH terms

  • Allosteric Regulation / drug effects*
  • Animals
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • GABA Agonists / chemical synthesis*
  • GABA Agonists / chemistry
  • GABA Agonists / pharmacology
  • GABA-A Receptor Agonists*
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Ligands
  • Mice
  • Molecular Structure
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Recombinant Proteins / agonists
  • Structure-Activity Relationship

Substances

  • 8-fluoroimidazo(1,2-a)pyridine
  • GABA Agonists
  • GABA-A Receptor Agonists
  • Imidazoles
  • Ligands
  • Pyridines
  • Recombinant Proteins