title: Synthesis and preliminary pharmacological results on new naphthalene derivatives as 5-HT(4) receptor ligands.
abstract: The indole derivative GR 113808 is currently used as the reference ligand for labelling the 5-HT(4) serotoninergic receptors. Previous works in our laboratories established the bioisosteric equivalency of the indole heterocycle and naphthalene in a series of melatonin receptor ligands. Based on this knowledge we designed new analogues of GR 113808 by introducing two bioisosteric modifications: firstly, the indole ring was replaced by a naphthalene one and secondly, the ester linkage was replaced by an amide group. Compound 8 emerged within this novel series as it displayed high and selective affinity at 5-HT(4) receptors (Ki 5-HT(4) = 6 nM, Ki 5-HT(3) = 100 nM, Ki values at other 5-HT receptors were higher than 1000 nM). Compound 8 is currently undergoing further pharmacological evaluation.
authors.affiliation: Institut de chimie pharmaceutique Albert Lespagnol, 3, rue du Professeur Laguesse, BP 83, 59006 cedex, Lille, France.
authors.forename: O
authors.initials: O
authors.lastname: Diouf
authors.forename: P
authors.initials: P
authors.lastname: Depreux
authors.forename: P
authors.initials: P
authors.lastname: Chavatte
authors.forename: J H
authors.initials: JH
authors.lastname: Poupaert
mesh_terms: D007211:Indoles / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011985:Receptors, Serotonin / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012702:Serotonin Antagonists / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry
chemical_list: D007211:Indoles; D008024:Ligands; D009281:Naphthalenes; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D044422:Receptors, Serotonin, 5-HT4; C082871:GR 113808