2. Academic Validation
  3. Melatonergic ligands: Design, synthesis and pharmacological evaluation of novel series of naphthofuranic derivatives

Melatonergic ligands: Design, synthesis and pharmacological evaluation of novel series of naphthofuranic derivatives

  • Eur J Med Chem. 2016 Feb 15:109:360-70. doi: 10.1016/j.ejmech.2015.12.047.
Elodie Landagaray 1,  Mohamed Ettaoussi 2,  Romain Duroux 3,  Jean A Boutin 4,  Daniel-Henri Caignard 5,  Philippe Delagrange 5,  Patricia Melnyk 3,  Pascal Berthelot 3,  Saïd Yous 6
Affiliations

Affiliations

  • 1 Université de Lille, F-59000, Lille, France; UDSL, UFR Pharmacie, F-59000, Lille, France.
  • 2 Université de Lille, F-59000, Lille, France; UDSL, UFR Pharmacie, F-59000, Lille, France. Electronic address: m.ettaoussi@yahoo.fr.
  • 3 Université de Lille, F-59000, Lille, France; UDSL, UFR Pharmacie, F-59000, Lille, France; INSERM, UMR-S1172, F-59000, Lille, France.
  • 4 Biotechnologies, Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, 78290, Croissy-sur-Seine, France.
  • 5 Unité de Recherche Chimie Neurosciences, Institut de Recherches Servier, 78290, Croissy-sur-Seine, France.
  • 6 Université de Lille, F-59000, Lille, France; UDSL, UFR Pharmacie, F-59000, Lille, France; INSERM, UMR-S1172, F-59000, Lille, France. Electronic address: said.yous@univ-lille2.fr.
PMID: 26820449 DOI: 10.1016/j.ejmech.2015.12.047
Abstract

Following our research for new melatonergic ligands, herein we report the design, synthesis and biological evaluation of new series of naphthofuranic derivatives as MT1 and MT2 ligands. Binding affinity results of the prepared compounds revealed good binding affinities at both Melatonin Receptor subtypes. Particularly, compound 6a behaved as an MT1 partial agonist and MT2 full agonist and exhibited an excellent binding affinity at MT2 (Ki = 0.09 nM). In addition, lateral chain displacement from position 1 to 2 of the furan core had no effect on the binding affinity at both MT1 and MT2, while elongation of this side chain, led to decreased melatonergic binding affinities.

Keywords

MT(1); MT(2); Melatonin; Naphthofuranic derivatives; Partial agonist.

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