Synthesis of 2-arylfuro[3,2-b]pyridines: Effect of the C2-aryl group on melatoninergic activity

Eur J Med Chem. 2016 Feb 15:109:268-75. doi: 10.1016/j.ejmech.2016.01.008. Epub 2016 Jan 12.


We report herein an efficient synthesis of 2-substituted furo[3,2-b]pyridines and their biological evaluation as melatonin receptors ligands. The proposed eight-step sequence ending with a Suzuki coupling allowed a rapid access to various analogues. The steric hindrance and the conformation of the aryl group in C2-position were evaluated regarding the selectivity of the molecule for one of the two high affinity melatonin receptors as well as the activity profile of the compound. Introduction of 1-naphthyl substituent gave the best result in terms of selectivity with a MT1/MT2 ratio of about 150 (MT1 Ki = 198 nM, MT2 Ki = 1.3 nM).

Keywords: Furopyridine; Melatonin receptors; Melatoninergic activity; SAR.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetulus
  • HEK293 Cells
  • Humans
  • Naphthalenes / chemical synthesis
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Protein Binding
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / pharmacology*
  • Receptor, Melatonin, MT1 / metabolism*
  • Receptor, Melatonin, MT2 / metabolism*
  • Structure-Activity Relationship


  • Naphthalenes
  • Pyridines
  • Receptor, Melatonin, MT1
  • Receptor, Melatonin, MT2