title: A new series of potent benzodiazepine gamma-secretase inhibitors.
abstract: A new series of benzodiazepine-containing gamma-secretase inhibitors with potential use in the treatment of Alzheimer's disease is disclosed. Structure-activity relationships of the pendant hydrocinnamate side-chain which led to the preparation of highly potent inhibitors are described.
authors.affiliation: Department of Medicinal Chemistry, The Neuroscience Research Centre, Merck, Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Essex Harlow, CM20 2QR, UK. ian_churcher@merck.com
authors.forename: Ian
authors.initials: I
authors.lastname: Churcher
authors.forename: Kate
authors.initials: K
authors.lastname: Ashton
authors.forename: John W
authors.initials: JW
authors.lastname: Butcher
authors.forename: Earl E
authors.initials: EE
authors.lastname: Clarke
authors.forename: Timothy
authors.initials: T
authors.lastname: Harrison
authors.forename: Huw D
authors.initials: HD
authors.lastname: Lewis
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Owens
authors.forename: Martin R
authors.initials: MR
authors.lastname: Teall
authors.forename: Susie
authors.initials: S
authors.lastname: Williams
authors.forename: Jonathan D J
authors.initials: JD
authors.lastname: Wrigley
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents; D008968:Molecular Conformation; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007202:Indicators and Reagents; D011480:Protease Inhibitors; D001569:Benzodiazepines; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human