Discovery of Begacestat, a Notch-1-Sparing γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease

Discovery of Begacestat, a Notch-1-Sparing γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease Discovery of (R)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-Cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007): Metabolically Stable γ-Secretase Inhibitors that Selectively Inhibit the Production of Amyloid-β over Notch Synthesis and structure–activity relationship of a novel series of heterocyclic sulfonamide γ-secretase inhibitors Discovery of a Series of Efficient, Centrally Efficacious BACE1 Inhibitors through Structure-Based Drug Design Diamide amino-imidazoles: A novel series of γ-secretase inhibitors for the treatment of Alzheimer’s disease Targeting the BACE1 Active Site Flap Leads to a Potent Inhibitor That Elicits Robust Brain Aβ Reduction in Rodents Discovery of Potent and Centrally Active 6-Substituted 5-Fluoro-1,3-dihydro-oxazine β-Secretase (BACE1) Inhibitors via Active Conformation Stabilization Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators SAR studies of acidic dual γ-secretase/PPARγ modulators Preparation and biological evaluation of BACE1 inhibitors: Leveraging trans-cyclopropyl moieties as ligand efficient conformational constraints