title: New melatonin (MT1/MT2) ligands: design and synthesis of (8,9-dihydro-7H-furo[3,2-f]chromen-1-yl) derivatives.
abstract: Herein we describe the synthesis of novel tricyclic analogues issued from the rigidification of the methoxy group of the benzofuranic analogue of melatonin as MT1 and MT2 ligands. Most of the synthesized compounds displayed high binding affinities at MT1 and MT2 receptors subtypes. Compound 6b (MT1, Ki=0.07nM; MT2, Ki=0.08nM) exhibited with the vinyl 6c and allyl 6d the most interesting derivatives of this series. Functional activity of these compounds showed full agonist activity with EC50 in the nanomolar range. Compounds 6a (EC50=0.8nM and Emax=98%) and 6b (EC50=0.2nM and Emax=121%) exhibited good pharmacological profiles.
authors.affiliation: Univ. Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Landagaray
authors.affiliation: Univ. Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France. Electronic address: m.ettaoussi@yahoo.fr.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ettaoussi
authors.affiliation: Univ. Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Leclerc
authors.affiliation: Univ. Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France.
authors.forename: Balla
authors.initials: B
authors.lastname: Traoré
authors.affiliation: Biotechnologies, Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, 78290 Croissy-sur-Seine, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Perez
authors.affiliation: Biotechnologies, Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, 78290 Croissy-sur-Seine, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Nosjean
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 Recherches et Découvertes en Neurosciences, Institut de Recherches Servier, 78290 Croissy-sur-Seine, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.affiliation: Univ. Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Berthelot
authors.affiliation: Univ. Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France.
authors.forename: Saïd
authors.initials: S
authors.lastname: Yous
mesh_terms: D000577:Amides / Q000737:chemistry; D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D016466:CHO Cells / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003412:Cricetulus; D057809:HEK293 Cells / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008550:Melatonin / Q000819:agonists / Q000031:analogs & derivatives* / Q000378:metabolism; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D001572:Benzofurans; D008024:Ligands; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008550:Melatonin
keywords: Benzofuran derivatives; CHO; Chinese Hamster Ovary; HEK; Human Embryonic Kidney; MLT; MT(1); MT(2)-selectivity; Melatonin; [(35)S]-GTPγS; guanosine-5′[γ-(35)S]-triphosphate; melatonin