title: Melatonergic ligands: Design, synthesis and pharmacological evaluation of novel series of naphthofuranic derivatives.
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.
authors.affiliation: Université de Lille, F-59000, Lille, France; UDSL, UFR Pharmacie, F-59000, Lille, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Landagaray
authors.affiliation: Université de Lille, F-59000, Lille, France; UDSL, UFR Pharmacie, F-59000, Lille, France. Electronic address: m.ettaoussi@yahoo.fr.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ettaoussi
authors.affiliation: Université de Lille, F-59000, Lille, France; UDSL, UFR Pharmacie, F-59000, Lille, France; INSERM, UMR-S1172, F-59000, Lille, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Duroux
authors.affiliation: Biotechnologies, Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, 78290, Croissy-sur-Seine, France.
authors.forename: Jean A
authors.initials: JA
authors.lastname: Boutin
authors.affiliation: Unité de Recherche Chimie Neurosciences, Institut de Recherches Servier, 78290, Croissy-sur-Seine, France.
authors.forename: Daniel-Henri
authors.initials: DH
authors.lastname: Caignard
authors.affiliation: Unité de Recherche Chimie Neurosciences, Institut de Recherches Servier, 78290, Croissy-sur-Seine, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.affiliation: Université de Lille, F-59000, Lille, France; UDSL, UFR Pharmacie, F-59000, Lille, France; INSERM, UMR-S1172, F-59000, Lille, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Melnyk
authors.affiliation: Université de Lille, F-59000, Lille, France; UDSL, UFR Pharmacie, F-59000, Lille, France; INSERM, UMR-S1172, F-59000, Lille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Berthelot
authors.affiliation: 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.
authors.forename: Saïd
authors.initials: S
authors.lastname: Yous
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D015195:Drug Design; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008550:Melatonin / Q000031:analogs & derivatives / Q000378:metabolism; D009281:Naphthalenes / Q000737:chemistry* / Q000494:pharmacology*; D044122:Receptor, Melatonin, MT1 / Q000819:agonists / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000819:agonists / Q000378:metabolism*
chemical_list: D005663:Furans; D008024:Ligands; D009281:Naphthalenes; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008550:Melatonin
keywords: MT(1); MT(2); Melatonin; Naphthofuranic derivatives; Partial agonist