title: Synthesis and pharmacological evaluation of dual ligands for melatonin (MT1/MT2) and serotonin 5-HT2C receptor subtypes (II).
abstract: In this paper we report the investigation of C-3 and β-acetamide positions of agomelatine analogues. Concomitant insertion of a hydroxymethyl in the β-acetamide position and aliphatic groups in C-3 position produced a positive effect on both melatonin (MT1, MT2) and serotonin (5-HT2C) binding affinities. In particular, the allyl 6b and ethyl 15a represented the more interesting compounds of this series. Furthermore, the introduction of methyl cycloalkyl groups (compounds 11a, 12a) exhibited no change in both MT2 and 5-HT2C binding affinities while a decrease of MT1 binding affinity occurred leading to an MT2 selectivity. Finally, the acetamide modulation has led to methyl thiourea 11h, with a weak MT2 selectivity.
authors.affiliation: Université Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France; INSERM UMR1172, F-59000 Lille, France. Electronic address: m.ettaoussi@yahoo.fr.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ettaoussi
authors.affiliation: Université Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France; INSERM UMR1172, F-59000 Lille, France.
authors.forename: Basile
authors.initials: B
authors.lastname: Pérès
authors.affiliation: Université Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France; INSERM UMR1172, F-59000 Lille, France.
authors.forename: Aïcha
authors.initials: A
authors.lastname: Errazani
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 Recherches et Découvertes en 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: Université Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France; INSERM UMR1172, F-59000 Lille, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Melnyk
authors.affiliation: Université Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France; INSERM UMR1172, F-59000 Lille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Berthelot
authors.affiliation: Université Lille Nord de France, F-59000 Lille, France; UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France; INSERM UMR1172, F-59000 Lille, France. Electronic address: said.yous@univ-lille2.fr.
authors.forename: Saïd
authors.initials: S
authors.lastname: Yous
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D044122:Receptor, Melatonin, MT1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D013329:Structure-Activity Relationship; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D008024:Ligands; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D044405:Receptor, Serotonin, 5-HT2C; C084711:agomelatine; D009281:Naphthalenes
keywords: Agomelatine; MT(2)-Selectivity; Melatonin receptors; Modulation; Serotonin 5-HT(2C) receptor