title: A novel series of potent gamma-secretase inhibitors based on a benzobicyclo[4.2.1]nonane core.
abstract: A new series of gamma-secretase inhibitors was developed from an in-house screening hit based on a benzobicyclo[4.2.1]nonane core. Lead optimisation studies led to the development of a series of potent inhibitors and in vivo efficacy was demonstrated.
authors.affiliation: Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK. stephen_lewis@merck.com
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lewis
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Smith
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Neduvelil
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Stevenson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Lindon
authors.forename: A Brian
authors.initials: AB
authors.lastname: Jones
authors.forename: Mark S
authors.initials: MS
authors.lastname: Shearman
authors.forename: Dirk
authors.initials: D
authors.lastname: Beher
authors.forename: Earl
authors.initials: E
authors.lastname: Clarke
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Best
authors.forename: James E
authors.initials: JE
authors.lastname: Peachey
authors.forename: Timothy
authors.initials: T
authors.lastname: Harrison
authors.forename: J Luis
authors.initials: JL
authors.lastname: Castro
mesh_terms: D000473:Alkanes / Q000138:chemical synthesis* / Q000494:pharmacology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D051379:Mice; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000473:Alkanes; D000577:Amides; D000588:Amines; D006571:Heterocyclic Compounds; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; C017573:nonane