title: Synthesis of new N-(arylcyclopropyl)acetamides and N-(arylvinyl)acetamides as conformationally-restricted ligands for melatonin receptors.
abstract: N-(Arylcyclopropyl)acetamides and N-(arylvinyl)acetamides or methyl ureas have been prepared as constrained analogues of melatonin. The affinity of these new compounds for chicken brain melatonin receptors and recombinant human MT(1) and MT(2) receptors was evaluated using 2-[(125)I]-iodomelatonin as radioligand. Strict ethylenic or cyclopropyl analogues of the commercialized agonist agomelatine (Valdoxan®) were equipotent to agomelatine in binding bioassays. However, the ethylenic analogue was more effective than the cyclopropyl one in the melanophore aggregation bioassay, but was still less potent than the disubstituted 2,7-dimethoxy-naphtalenic compounds.
authors.affiliation: Université de Paris-Sud, BIOCIS - UMR CNRS 8076, Faculté de Pharmacie, 5 rue J. B. Clément, 92296 Châtenay-Malabry, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Morellato
authors.forename: Marie
authors.initials: M
authors.lastname: Lefas-Le Gall
authors.forename: Michel
authors.initials: M
authors.lastname: Langlois
authors.forename: Daniel-Henri
authors.initials: DH
authors.lastname: Caignard
authors.forename: Pierre
authors.initials: P
authors.lastname: Renard
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.forename: Monique
authors.initials: M
authors.lastname: Mathé-Allainmat
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002645:Chickens; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D044094:Receptors, Melatonin / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000081:Acetamides; D003521:Cyclopropanes; D008024:Ligands; D044094:Receptors, Melatonin; D011994:Recombinant Proteins; D014753:Vinyl Compounds