Design and synthesis of 2-phenylimidazo[1,2-a]pyridines as a novel class of melatonin receptor ligands

Eur J Med Chem. 2011 Sep;46(9):4252-7. doi: 10.1016/j.ejmech.2011.06.030. Epub 2011 Jul 1.

Abstract

A novel class of imidazo[1,2-a]pyridines as melatonin receptor ligands is designed and synthesized. The affinities of 3-(6-methoxy-2-phenylimidazo[1,2-a]pyridine-3-yl)-N-methyl-propionamide 8, N-[2-(6-methoxy-2-phenylimidazo[1,2-a]pyridine-3-yl)-ethyl]-acetamide 13 and N-(1-hydroxy-3-(5-methoxy-2-phenyl-1H-indol-3-yl)propan-2-yl)acetamide 18 are evaluated for binding on melatonin receptors. Compound 8 present good selectivity for MT(2) over MT(1) (MT(1)/MT(2) = 19) and compound 13 have good affinities for both MT(1) (Ki :28 nM) and MT(2) (Ki : 8 nM).

MeSH terms

  • Animals
  • CHO Cells
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Drug Design
  • Drug Evaluation, Preclinical
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / metabolism
  • Pyridines / pharmacology*
  • Receptors, Melatonin / drug effects*
  • Receptors, Melatonin / metabolism
  • Spectrophotometry, Infrared

Substances

  • Ligands
  • Pyridines
  • Receptors, Melatonin