Abstract
The structural modification of a series of [3.3.1] bicyclic sulfonamide based gamma-secretase inhibitors is described. Appropriate substitution on the bicyclic scaffold provides a significant increase in the metabolic stability of the compounds resulting in an improved in vivo metabolic profile.
MeSH terms
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Alzheimer Disease / drug therapy
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Alzheimer Disease / enzymology*
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Bridged Bicyclo Compounds / chemistry*
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Bridged Bicyclo Compounds / pharmacology
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Bridged Bicyclo Compounds / therapeutic use
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Humans
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Protease Inhibitors / chemistry*
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Protease Inhibitors / pharmacology
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Protease Inhibitors / therapeutic use
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Structure-Activity Relationship
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Sulfonamides / chemistry*
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Sulfonamides / pharmacology
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Sulfonamides / therapeutic use
Substances
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Bridged Bicyclo Compounds
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Protease Inhibitors
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Sulfonamides
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Amyloid Precursor Protein Secretases