Abstract
We describe an optimized series of acyclic hydroxyethylamine transition state isosteres of beta-secretase that incorporates a variety of P(2) side chains that yield potent inhibitors with excellent cellular activity. A 2.2A crystal structure of compound 13 is shown.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Alzheimer Disease / drug therapy*
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Amyloid Precursor Protein Secretases / chemistry
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Carbamates / chemical synthesis
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Carbamates / chemistry*
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Carbamates / pharmacology
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Cells, Cultured
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Drug Design
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Humans
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Molecular Structure
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Protease Inhibitors / chemical synthesis
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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 / chemical synthesis
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Sulfonamides / chemistry*
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Sulfonamides / pharmacology
Substances
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Carbamates
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Protease Inhibitors
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Sulfonamides
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Amyloid Precursor Protein Secretases