title: BACE-1 hydroxyethylamine inhibitors using novel edge-to-face interaction with Arg-296.
abstract: Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. Herein, is described a series of potent inhibitors based on an hydroxyethylamine (HEA) transition state mimetic template. These inhibitors interact with the non prime side of the enzyme using a novel edge-to-face interaction with Arg-296.
authors.affiliation: Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, New Frontiers Science Park, Harlow, Essex, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Clarke
authors.forename: Leanne
authors.initials: L
authors.lastname: Cutler
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Demont
authors.forename: Colin
authors.initials: C
authors.lastname: Dingwall
authors.forename: Rachel
authors.initials: R
authors.lastname: Dunsdon
authors.forename: Julie
authors.initials: J
authors.lastname: Hawkins
authors.forename: Colin
authors.initials: C
authors.lastname: Howes
authors.forename: Ishrut
authors.initials: I
authors.lastname: Hussain
authors.forename: Graham
authors.initials: G
authors.lastname: Maile
authors.forename: Rosalie
authors.initials: R
authors.lastname: Matico
authors.forename: Julie
authors.initials: J
authors.lastname: Mosley
authors.forename: Alan
authors.initials: A
authors.lastname: Naylor
authors.forename: Alistair
authors.initials: A
authors.lastname: O'Brien
authors.forename: Sally
authors.initials: S
authors.lastname: Redshaw
authors.forename: Paul
authors.initials: P
authors.lastname: Rowland
authors.forename: Virginie
authors.initials: V
authors.lastname: Soleil
authors.forename: Kathrine J
authors.initials: KJ
authors.lastname: Smith
authors.forename: Sharon
authors.initials: S
authors.lastname: Sweitzer
authors.forename: Pam
authors.initials: P
authors.lastname: Theobald
authors.forename: David
authors.initials: D
authors.lastname: Vesey
authors.forename: Daryl S
authors.initials: DS
authors.lastname: Walter
authors.forename: Gareth
authors.initials: G
authors.lastname: Wayne
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D005021:Ethylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D005021:Ethylamines; D011480:Protease Inhibitors; D001120:Arginine; D053829:Amyloid Precursor Protein Secretases