title: Discovery of GlyT1 inhibitors with improved pharmacokinetic properties.
abstract: Glycine transporter 1 (GlyT1) represents a novel target for the treatment of schizophrenia via the potentiation of glutamatergic NMDA receptors. The discovery of 4,4-disubstituted piperidine inhibitors of GlyT1 which exhibit improved pharmacokinetic properties, including oral bioavailability, is discussed.
authors.affiliation: Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Merck & Co., Inc., PO Box 4, West Point, PA 19486, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Wolkenberg
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Zhao
authors.forename: David D
authors.initials: DD
authors.lastname: Wisnoski
authors.forename: William H
authors.initials: WH
authors.lastname: Leister
authors.forename: Julie
authors.initials: J
authors.lastname: O'Brien
authors.forename: Wei
authors.initials: W
authors.lastname: Lemaire
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
authors.forename: Marlene A
authors.initials: MA
authors.lastname: Jacobson
authors.forename: Cyrille
authors.initials: C
authors.lastname: Sur
authors.forename: Gene G
authors.initials: GG
authors.lastname: Kinney
authors.forename: Doug J
authors.initials: DJ
authors.lastname: Pettibone
authors.forename: Philip R
authors.initials: PR
authors.lastname: Tiller
authors.forename: Sheri
authors.initials: S
authors.lastname: Smith
authors.forename: Christopher
authors.initials: C
authors.lastname: Gibson
authors.forename: Bennett K
authors.initials: BK
authors.lastname: Ma
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Polsky-Fisher
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
mesh_terms: D000818:Animals; D004285:Dogs; D055808:Drug Discovery / Q000379:methods*; D005998:Glycine / Q000096:biosynthesis; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008811:Mice, Inbred DBA; D016202:N-Methylaspartate / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D013379:Substrate Specificity; D013449:Sulfonamides / Q000138:chemical synthesis
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; D010880:Piperidines; D013449:Sulfonamides; D016202:N-Methylaspartate; D005998:Glycine