title: Design, synthesis and structure-activity relationship of simple bis-amides as potent inhibitors of GlyT1.
abstract: Several novel classes of potent and small amide-type inhibitors of glycine transport (GlyT1) were developed through sequential simplification of a benzodiazepinone-lead structure identified from a high-throughput screening. The most potent compounds of these structurally simple classes show low nanomolar inhibition at the GlyT1 target.
authors.affiliation: F. Hoffmann-La Roche Ltd., Pharmaceutical Research Basel, Discovery Chemistry, CH-4070 Basel, Switzerland. synese.jolidon@roche.com
authors.forename: Synèse
authors.initials: S
authors.lastname: Jolidon
authors.forename: Daniela
authors.initials: D
authors.lastname: Alberati
authors.forename: Adam
authors.initials: A
authors.lastname: Dowle
authors.forename: Holger
authors.initials: H
authors.lastname: Fischer
authors.forename: Dominik
authors.initials: D
authors.lastname: Hainzl
authors.forename: Robert
authors.initials: R
authors.lastname: Narquizian
authors.forename: Roger
authors.initials: R
authors.lastname: Norcross
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pinard
mesh_terms: D000577:Amides / Q000737:chemistry*; D000818:Animals; D001570:Benzodiazepinones / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008861:Microsomes / Q000737:chemistry; D008956:Models, Chemical; D010539:Permeability; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D001570:Benzodiazepinones; D050487:Glycine Plasma Membrane Transport Proteins; C493268:SLC6A9 protein, human