title: Discovery of N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamides as novel, selective and potent GlyT1 inhibitors.
abstract: Employing an iterative analogue library approach, novel potent and selective glycine transporter 1 (GlyT1) inhibitors containing a 4-pyridin-2-ylpiperidine sulfonamide have been discovered. These inhibitors are devoid of time-dependent CYP inhibition activity and exhibit improved aqueous solubility versus the corresponding 4-phenylpiperidine analogues.
authors.affiliation: Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Merck & Co., Inc., WP-14-1, PO Box 4 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Zhao
authors.forename: William H
authors.initials: WH
authors.lastname: Leister
authors.forename: Julie A
authors.initials: JA
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: George D
authors.initials: GD
authors.lastname: Hartman
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.forename: Scott E
authors.initials: SE
authors.lastname: Wolkenberg
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods*; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D012995:Solubility; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D001549:Benzamides; D050487:Glycine Plasma Membrane Transport Proteins; D010880:Piperidines; C493268:SLC6A9 protein, human; D013449:Sulfonamides