title: Imidazo[1,2-a]pyridines: orally active positive allosteric modulators of the metabotropic glutamate 2 receptor.
abstract: Advanced leads of an imidazopyridine series of positive allosteric modulators of the metabotropic glutamate 2 (mGlu2) receptor are reported. The optimization of in vitro ADMET and in vivo pharmacokinetic properties led to the identification of 27o. With good potency and selectivity for the mGlu2 receptor, 27o affected sleep-wake architecture in rats after oral treatment, which we have previously shown to be indicative of mGlu2 receptor-mediated central activity.
authors.affiliation: Neuroscience Medicinal Chemistry, Janssen Research & Development, Janssen-Cilag S.A., Jarama 75, 45007-Toledo, Spain. atrabanc@its.jnj.com
authors.forename: Andrés A
authors.initials: AA
authors.lastname: Trabanco
authors.forename: Gary
authors.initials: G
authors.lastname: Tresadern
authors.forename: Gregor J
authors.initials: GJ
authors.lastname: Macdonald
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Vega
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: de Lucas
authors.forename: Encarnación
authors.initials: E
authors.lastname: Matesanz
authors.forename: Aránzazu
authors.initials: A
authors.lastname: García
authors.forename: María Lourdes
authors.initials: ML
authors.lastname: Linares
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Alonso de Diego
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Alonso
authors.forename: Daniel
authors.initials: D
authors.lastname: Oehlrich
authors.forename: Abdelah
authors.initials: A
authors.lastname: Ahnaou
authors.forename: Wilhelmus
authors.initials: W
authors.lastname: Drinkenburg
authors.forename: Claire
authors.initials: C
authors.lastname: Mackie
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Andrés
authors.forename: Hilde
authors.initials: H
authors.lastname: Lavreysen
authors.forename: José María
authors.initials: JM
authors.lastname: Cid
mesh_terms: D000284:Administration, Oral; D000494:Allosteric Regulation; D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D065607:Cytochrome P-450 Enzyme Inhibitors; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects; D013329:Structure-Activity Relationship; D014851:Wakefulness / Q000187:drug effects
chemical_list: C573840:8-chloro-7-(7-chloro-1H-indol-5-yl)-3-(2,2,2-trifluoroethyl)imidazo(1,2-a)pyridine; D019086:Bridged Bicyclo Compounds, Heterocyclic; D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D007211:Indoles; D007473:Ion Channels; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2