title: Design and synthesis of potential dual NK(1)/NK(3) receptor antagonists.
abstract: The tachykinin NK1 and NK3 receptors are a novel drug target for schizophrenia in order to treat not only the positive and cognitive symptoms, but also the associated co-morbid depression and sleep disturbances associated with the disease. A novel class of peptidomimetic derivatives based on a versatile phenylglycine central core was synthesized and tested in vitro as dual NK1/NK3 receptor antagonists. From this series emerged compounds with good NK1 receptor affinity, although only modest dual NK1/NK3 receptor affinity was observed with one of these analogs.
authors.affiliation: Department of Chemistry, Université de Montréal, PO Box 6128, Station Centre-Ville, Montréal, Que. H3C 3J7, Canada. Electronic address: stephen.hanessian@umontreal.ca.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanessian
authors.affiliation: Department of Chemistry, Université de Montréal, PO Box 6128, Station Centre-Ville, Montréal, Que. H3C 3J7, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Babonneau
authors.affiliation: Department of Chemistry, Université de Montréal, PO Box 6128, Station Centre-Ville, Montréal, Que. H3C 3J7, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boyer
authors.affiliation: Department of Psychopharmacology, Institut de Recherches Servier, 125 Chemin de Ronde, 78290 Croissy/Seine, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Mannoury la Cour
authors.affiliation: Department of Psychopharmacology, Institut de Recherches Servier, 125 Chemin de Ronde, 78290 Croissy/Seine, France.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Millan
authors.affiliation: Neuroscience Chemistry Research Unit, Institut de Recherches Servier, 125 Chemin de Ronde, 78290 Croissy-sur-Seine, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: De Nanteuil
mesh_terms: D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000378:metabolism; D015195:Drug Design; D064729:Neurokinin-1 Receptor Antagonists / Q000138:chemical synthesis* / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D018042:Receptors, Neurokinin-3
keywords: NK(1)/NK(3) receptor antagonists; Neurokinin receptors; Peptidomimetic; Schizophrenia