title: New positive allosteric modulators of the metabotropic glutamate receptor 2 (mGluR2): identification and synthesis of N-propyl-8-chloro-6-substituted isoquinolones.
abstract: A series of N-propyl-8-chloro-6-substituted isoquinolones was identified as positive allosteric modulators of metabotropic glutamate receptor 2 (mGluR2 PAM) via high throughput screening (HTS). The subsequent synthesis and initial SAR exploration that led to the identification of compound 28 is described.
authors.affiliation: Medicinal Chemistry, Janssen Research & Development, Janssen-Cilag SA, Toledo, Spain. atrabanc@its.jnj.com
authors.forename: Andrés A
authors.initials: AA
authors.lastname: Trabanco
authors.forename: Guillaume
authors.initials: G
authors.lastname: Duvey
authors.forename: José María
authors.initials: JM
authors.lastname: Cid
authors.forename: Gregor J
authors.initials: GJ
authors.lastname: Macdonald
authors.forename: Philippe
authors.initials: P
authors.lastname: Cluzeau
authors.forename: Vanthea
authors.initials: V
authors.lastname: Nhem
authors.forename: Rocco
authors.initials: R
authors.lastname: Furnari
authors.forename: Nadia
authors.initials: N
authors.lastname: Behaj
authors.forename: Géraldine
authors.initials: G
authors.lastname: Poulain
authors.forename: Terry
authors.initials: T
authors.lastname: Finn
authors.forename: Hilde
authors.initials: H
authors.lastname: Lavreysen
authors.forename: Sonia
authors.initials: S
authors.lastname: Poli
authors.forename: Alexandre
authors.initials: A
authors.lastname: Raux
authors.forename: Yves
authors.initials: Y
authors.lastname: Thollon
authors.forename: Nicolas
authors.initials: N
authors.lastname: Poirier
authors.forename: David
authors.initials: D
authors.lastname: D'Addona
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Andrés
authors.forename: Robert
authors.initials: R
authors.lastname: Lutjens
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Le Poul
authors.forename: Hassan
authors.initials: H
authors.lastname: Imogai
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rocher
mesh_terms: D000494:Allosteric Regulation; D057166:High-Throughput Screening Assays; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D011725:Pyridines; D015363:Quinolones; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2