title: 3,4-Fused cyclohexyl sulfones as gamma-secretase inhibitors.
abstract: The 3,4-fused sulfamides, sulfonamides and sulfone have been identified as highly potent gamma-secretase inhibitors. Evaluation of the SAR of substitution within these series has allowed the identification of a range of compounds which significantly reduce brain A beta in transgenic mouse models and thus have potential as possible treatments for Alzheimer's disease.
authors.affiliation: Department of Medicinal Chemistry, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. Duncan_shaw@merck.com
authors.forename: Duncan
authors.initials: D
authors.lastname: Shaw
authors.forename: Jonathan
authors.initials: J
authors.lastname: Best
authors.forename: Kevin
authors.initials: K
authors.lastname: Dinnell
authors.forename: Alan
authors.initials: A
authors.lastname: Nadin
authors.forename: Mark
authors.initials: M
authors.lastname: Shearman
authors.forename: Christine
authors.initials: C
authors.lastname: Pattison
authors.forename: James
authors.initials: J
authors.lastname: Peachey
authors.forename: Michael
authors.initials: M
authors.lastname: Reilly
authors.forename: Brian
authors.initials: B
authors.lastname: Williams
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wrigley
authors.forename: Timothy
authors.initials: T
authors.lastname: Harrison
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D018360:Crystallography, X-Ray; D003500:Cyclization; D010450:Endopeptidases / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D011480:Protease Inhibitors; D013450:Sulfones; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse