title: Novel conformationally constrained analogues of agomelatine as new melatoninergic ligands.
abstract: Novel conformationally restricted analogues of agomelatine were synthesized and pharmacologically evaluated at MT₁ and MT₂ melatoninergic receptors. Replacement of the N-acetyl side chain of agomelatine by oxathiadiazole-2-oxide (compound 3), oxadiazole-5(4H)-one (compound 4), tetrazole (compound 5), oxazolidinone (compound 7a), pyrrolidinone (compound 7b), imidazolidinedione (compound 12), thiazole (compounds 13 and 14) and isoxazole moieties (compound 15) led to a decrease of the melatoninergic binding affinities, particularly at MT₁. Compounds 7a and 7b exhibiting nanomolar affinity towards the MT₂ receptors subtypes have shown the most interesting pharmacological results of this series with the appearance of a weak MT₂-selectivity.
authors.affiliation: University of Lille Nord de France, F-59000 Lille, France. marouanr@yahoo.fr
authors.forename: Marouan
authors.initials: M
authors.lastname: Rami
authors.forename: Elodie
authors.initials: E
authors.lastname: Landagaray
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ettaoussi
authors.forename: Koussayla
authors.initials: K
authors.lastname: Boukhalfa
authors.forename: Daniel-Henri
authors.initials: DH
authors.lastname: Caignard
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.forename: Pascal
authors.initials: P
authors.lastname: Berthelot
authors.forename: Saïd
authors.initials: S
authors.lastname: Yous
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D007555:Isoxazoles / Q000378:metabolism; D008024:Ligands; D023303:Oxazolidinones / Q000378:metabolism; D011760:Pyrrolidinones / Q000378:metabolism; D011869:Radioligand Assay; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D007555:Isoxazoles; D008024:Ligands; D023303:Oxazolidinones; D011760:Pyrrolidinones; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D013777:Tetrazoles; D013844:Thiazoles; C084711:agomelatine; D009281:Naphthalenes; C045574:1H-tetrazole