Abstract
The synthesis and gamma-secretase inhibition data for a series of carbamate-appended N-alkylsulfonamides are described. Carbamate 54 was found to significantly reduce brain Abeta in transgenic mice. 54 was also found to possess markedly improved brain levels in transgenic mice compared to previously disclosed 1 and 2.
MeSH terms
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Alzheimer Disease / metabolism
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Amyloid beta-Peptides / antagonists & inhibitors
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Amyloid beta-Peptides / metabolism
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Animals
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Brain / drug effects
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Brain / metabolism
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Carbamates / chemistry*
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Mice
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Mice, Transgenic
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Protease Inhibitors / chemistry*
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Protease Inhibitors / pharmacology*
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Structure-Activity Relationship
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Sulfonamides / chemistry*
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Sulfonamides / pharmacology*
Substances
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Amyloid beta-Peptides
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Carbamates
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Protease Inhibitors
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Sulfonamides
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Amyloid Precursor Protein Secretases