title: Identification of an Orally Bioavailable, Potent, and Selective Inhibitor of GlyT1.
abstract: Amalgamation of the structure-activity relationship of two series of GlyT1 inhibitors developed at Merck led to the discovery of a clinical candidate, compound 16 (DCCCyB), which demonstrated excellent in vivo occupancy of GlyT1 transporters in rhesus monkey as determined by displacement of a PET tracer ligand.
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Wesley P
authors.initials: WP
authors.lastname: Blackaby
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lewis
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Thomson
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Andrew S R
authors.initials: AS
authors.lastname: Jennings
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Goodacre
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Street
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Angus M
authors.initials: AM
authors.lastname: MacLeod
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pike
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Wood
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Steve
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Terry A
authors.initials: TA
authors.lastname: Brown
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Smith
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Gopalan
authors.initials: G
authors.lastname: Pillai
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Almond
authors.affiliation: Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Guscott
authors.affiliation: Research Imaging, Merck Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: H Donald
authors.initials: HD
authors.lastname: Burns
authors.affiliation: Research Imaging, Merck Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: Waisi
authors.initials: W
authors.lastname: Eng
authors.affiliation: Research Imaging, Merck Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: Christine
authors.initials: C
authors.lastname: Ryan
authors.affiliation: Research Imaging, Merck Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: Jacquelynn
authors.initials: J
authors.lastname: Cook
authors.affiliation: Research Imaging, Merck Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: Terence G
authors.initials: TG
authors.lastname: Hamill
keywords: DCCCyB; GlyT1; Inhibitor; PET tracer ligand; structure−activity relationship