title: Discovery of a potent and brain penetrant mGluR5 positive allosteric modulator.
abstract: This Letter describes the discovery of a novel series of mGluR5 positive allosteric modulators (PAMs). The lead compound, 11c, exhibits excellent potency (EC(50)=30 nM) in vitro, and reaches high brain levels in both rats and mice after oral administration.
authors.affiliation: Medicinal Chemistry Research DK, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. arit@lundbeck.com
authors.forename: Andreas
authors.initials: A
authors.lastname: Ritzén
authors.forename: Rikke
authors.initials: R
authors.lastname: Sindet
authors.forename: Morten
authors.initials: M
authors.lastname: Hentzer
authors.forename: Nannette
authors.initials: N
authors.lastname: Svendsen
authors.forename: Robbin M
authors.initials: RM
authors.lastname: Brodbeck
authors.forename: Christoffer
authors.initials: C
authors.lastname: Bundgaard
mesh_terms: D000284:Administration, Oral; D000480:Alkynes / Q000737:chemistry* / Q000494:pharmacology; D000494:Allosteric Regulation; D000818:Animals; D001921:Brain / Q000378:metabolism*; D055808:Drug Discovery; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; C578936:Grm5 protein, mouse; C578937:Grm5 protein, rat; D006571:Heterocyclic Compounds; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate