title: The discovery of a structurally novel class of inhibitors of the type 1 glycine transporter.
abstract: The type 1 glycine transporter plays an important in regulating homeostatic glycine levels in the brain that are relevant to the activation of the NMDA receptor by the excitatory neurotransmitter glutamate. We describe herein the structure-activity relationships (SAR) of a structurally novel class of GlyT1 inhibitors following on a lead derived from high throughput screening, which shows good selectivity for GlyT1 and potent activity in elevating CSF levels of glycine.
authors.affiliation: Pfizer Global Research and Development, Groton, CT 06340, United States. jal3rd@gmail.com
authors.forename: John A
authors.initials: JA
authors.lastname: Lowe
authors.forename: Xinjun
authors.initials: X
authors.lastname: Hou
authors.forename: Christopher
authors.initials: C
authors.lastname: Schmidt
authors.forename: F
authors.initials: F
authors.lastname: David Tingley
authors.forename: Stan
authors.initials: S
authors.lastname: McHardy
authors.forename: Monica
authors.initials: M
authors.lastname: Kalman
authors.forename: Shari
authors.initials: S
authors.lastname: Deninno
authors.forename: Mark
authors.initials: M
authors.lastname: Sanner
authors.forename: Karen
authors.initials: K
authors.lastname: Ward
authors.forename: Lorraine
authors.initials: L
authors.lastname: Lebel
authors.forename: Don
authors.initials: D
authors.lastname: Tunucci
authors.forename: James
authors.initials: J
authors.lastname: Valentine
authors.forename: Brian S
authors.initials: BS
authors.lastname: Bronk
authors.forename: Eric
authors.initials: E
authors.lastname: Schaeffer
mesh_terms: D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D005998:Glycine / Q000378:metabolism; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001372:Aza Compounds; D050487:Glycine Plasma Membrane Transport Proteins; D006574:Heterocyclic Compounds, 2-Ring; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine