A new series of potent benzodiazepine γ-secretase inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 2; pp. 179 - 183
• Main Authors: Churcher, Ian, Ashton, Kate, Butcher, John W., Clarke, Earl E., Harrison, Timothy, Lewis, Huw D., Owens, Andrew P., Teall, Martin R., Williams, Susie, Wrigley, Jonathan D.J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 20.01.2003; Elsevier
• Subjects: Amyloid Precursor Protein Secretases; Aspartic Acid Endopeptidases; Benzodiazepines - chemical synthesis; Benzodiazepines - pharmacology; Biological and medical sciences; Cell Line; Endopeptidases - metabolism; Humans; Indicators and Reagents; Medical sciences; Molecular Conformation; Neuropharmacology; Pharmacology. Drug treatments; Protease Inhibitors - chemical synthesis; Protease Inhibitors - pharmacology; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Structure-Activity Relationship; Enzyme; Alzheimer disease; Nitrogen heterocycle; Lactam; Enzyme inhibitor; In vitro; Amyloid precursor protein; Peptidases; Structure activity relation; β Amyloid protein; Bicyclic compound; Hydrolases; Benzodiazepine derivatives; Carboxamide; Benzenic compound; Aromatic compound; Fluorine Organic compounds; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00909-5

A new series of benzodiazepine-containing γ-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. The structure–activity relationships of a series of γ-secretase inhibitors are discussed.