title: Design, Synthesis, and Optimization of Balanced Dual NK1/NK3 Receptor Antagonists.
abstract: In connection with a program directed at potent and balanced dual NK1/NK3 receptor ligands, a focused exploration of an original class of peptidomimetic derivatives was performed. The rational design and molecular hybridization of a novel phenylalanine core series was achieved to maximize the in vitro affinity and antagonism at both human NK1 and NK3 receptors. This study led to the identification of a new potent dual NK1/NK3 antagonist with pK i values of 8.6 and 8.1, respectively.
authors.affiliation: Department of Chemistry, Université de Montréal , Station Centre-Ville, Montréal, Que. H3C 3J7, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanessian
authors.affiliation: Department of Chemistry, Université de Montréal , Station Centre-Ville, Montréal, Que. H3C 3J7, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jennequin
authors.affiliation: Department of Chemistry, Université de Montréal , Station Centre-Ville, Montréal, Que. H3C 3J7, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boyer
authors.affiliation: Department of Chemistry, Université de Montréal , 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 , Station Centre-Ville, Montréal, Que. H3C 3J7, Canada.
authors.forename: Udaykumar
authors.initials: U
authors.lastname: Soma
authors.affiliation: Department of Psychopharmacology, Institut de Recherches Servier, 125 Chemin de Ronde, 78290 Croissy-sur-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-sur-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
keywords: Schizophrenia; dual NK1/NK3 receptor antagonists; molecular hybridization; peptidomimetic