Fluorinated piperidine acetic acids as γ-secretase modulators
Copyright policy )Fluorinated piperidine acetic acids as γ-secretase modulators
We report herein a novel series of difluoropiperidine acetic acids as modulators of gamma-secretase. Synthesis of 2-aryl-3,3-difluoropiperidine analogs was facilitated by a unique and selective beta-difluorination with Selectfluor. Compounds 1f and 2c were selected for in vivo assessment and demonstrated selective lowering of Abeta42 in a genetically engineered mouse model of APP processing. Moreover, in a 7-day safety study, rats treated orally with compound 1f (250mg/kg per day, AUC(0-24)=2100microMh) did not exhibit Notch-related effects.
- United States Military Academy United States
- Merck & Co. United States
Amyloid beta-Peptides, Receptors, Notch, Mice, Transgenic, Diazonium Compounds, Fluorine, Acetates, Peptide Fragments, Rats, Disease Models, Animal, Mice, Piperidines, Animals, Amyloid Precursor Protein Secretases
Amyloid beta-Peptides, Receptors, Notch, Mice, Transgenic, Diazonium Compounds, Fluorine, Acetates, Peptide Fragments, Rats, Disease Models, Animal, Mice, Piperidines, Animals, Amyloid Precursor Protein Secretases
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