Transgenic mice (Tg2576) overexpressing the Swedish mutation of the human amyloid
precursor protein display biochemical, pathological, and behavioral markers consistent with …

The presenilin containing γ-secretase complex is responsible for the regulated
intramembraneous proteolysis of the amyloid precursor protein (APP), the Notch receptor, and a …

SAR on HTS hits 1 and 2 led to the potent, Notch-1-sparing GSI 9, which lowered brain Aβ
in Tg2576 mice at 100 mg/kg po. Converting the metabolically labile methyl groups in 9 to …

Alzheimer’s disease (ADa) was first described over a hundred years ago by Alois Alzheimer
as a dementia associated with the presence of extracellular insoluble β-amyloid plaques in …

The isozymes of prostaglandin G/H synthase (PGHS) are shown to be differentially inhibited
in vitro by currently marketed nonsteroidal anti-inflammatory drugs (NSAIDs) using …

Feldberg, Kellaway, and Trethewie12 a half century ago first recognized that stimulated
lung tissue can produce a material, SRS-A (slow reacting substance of anaphylaxis), which …

The present study demonstrated that acid-extracted platelet phospholipase A 2 (PLA 2 )
exhibited marked hydrolytic activity against both [1- 14 C]oleic acid- and [1- 14 C]arachidonic …

N-[(Arylmethoxy)phenyl] carboxylic acids, hydroxamic acids, tetrazoles, and sulfonyl
carboxamides. Potent orally active leukotri Page 1 240 J. Med. Chem. 33, 240-245 JV-[(Arylmethoxy)…

Development of a large-scale enantioselective synthesis of a lead compound containing a 3-aryl-3-trifluoromethyl-2-aminopropanol
core is described. A single isomer of 3,3-…

Using a cell-based assay, we have identified a new series of Notch-sparing γ-secretase
inhibitors from HTS screening leads 2a and 2e. Lead optimization studies led to the discovery of …