title: 3-Benzyl-1,3-oxazolidin-2-ones as mGluR2 positive allosteric modulators: Hit-to lead and lead optimization.
abstract: The discovery, synthesis and SAR of a novel series of 3-benzyl-1,3-oxazolidin-2-ones as positive allosteric modulators (PAMs) of mGluR2 is described. Expedient hit-to-lead work on a single HTS hit led to the identification of a ligand-efficient and structurally attractive series of mGluR2 PAMs. Human microsomal clearance and suboptimal physicochemical properties of the initial lead were improved to give potent, metabolically stable and orally available mGluR2 PAMs.
authors.affiliation: CNS Chemistry, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA.
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Duplantier
authors.forename: Ivan
authors.initials: I
authors.lastname: Efremov
authors.forename: John
authors.initials: J
authors.lastname: Candler
authors.forename: Angela C
authors.initials: AC
authors.lastname: Doran
authors.forename: Alan H
authors.initials: AH
authors.lastname: Ganong
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Haas
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Hanks
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Kraus
authors.forename: John T
authors.initials: JT
authors.lastname: Lazzaro
authors.forename: Jiemin
authors.initials: J
authors.lastname: Lu
authors.forename: Noha
authors.initials: N
authors.lastname: Maklad
authors.forename: Sheryl A
authors.initials: SA
authors.lastname: McCarthy
authors.forename: Theresa J
authors.initials: TJ
authors.lastname: O'Sullivan
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Rogers
authors.forename: Judith A
authors.initials: JA
authors.lastname: Siuciak
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Spracklin
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang