title: Synthesis of 2-arylfuro[3,2-b]pyridines: Effect of the C2-aryl group on melatoninergic activity.
abstract: We report herein an efficient synthesis of 2-substituted furo[3,2-b]pyridines and their biological evaluation as melatonin receptors ligands. The proposed eight-step sequence ending with a Suzuki coupling allowed a rapid access to various analogues. The steric hindrance and the conformation of the aryl group in C2-position were evaluated regarding the selectivity of the molecule for one of the two high affinity melatonin receptors as well as the activity profile of the compound. Introduction of 1-naphthyl substituent gave the best result in terms of selectivity with a MT1/MT2 ratio of about 150 (MT1 Ki = 198 nM, MT2 Ki = 1.3 nM).
authors.affiliation: Institut de Chimie Organique et Analytique, Université d'Orléans, UMR CNRS 7311, B.P. 6759, 45067 Orléans Cedex 2, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Couhert
authors.affiliation: Institut de Recherche Servier, Sciences Expérimentales, 125 Chemin de Ronde, 78290 Croissy, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.affiliation: Institut de Recherche Servier, Sciences Expérimentales, 125 Chemin de Ronde, 78290 Croissy, France.
authors.forename: Daniel-Henri
authors.initials: DH
authors.lastname: Caignard
authors.affiliation: Institut de Chimie Organique et Analytique, Université d'Orléans, UMR CNRS 7311, B.P. 6759, 45067 Orléans Cedex 2, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Chartier
authors.affiliation: Institut de Chimie Organique et Analytique, Université d'Orléans, UMR CNRS 7311, B.P. 6759, 45067 Orléans Cedex 2, France. Electronic address: franck.suzenet@univ-orleans.fr.
authors.forename: Franck
authors.initials: F
authors.lastname: Suzenet
authors.affiliation: Institut de Chimie Organique et Analytique, Université d'Orléans, UMR CNRS 7311, B.P. 6759, 45067 Orléans Cedex 2, France. Electronic address: gerald.guillaumet@univ-orleans.fr.
authors.forename: Gérald
authors.initials: G
authors.lastname: Guillaumet
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D057809:HEK293 Cells; D006801:Humans; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D009281:Naphthalenes; D011725:Pyridines; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2
keywords: Furopyridine; Melatonin receptors; Melatoninergic activity; SAR