Abstract
BACE-1 inhibition has the potential to provide a disease-modifying therapy for the treatment of Alzheimer's disease. Optimization of a first generation of BACE-1 inhibitors led to the discovery of novel hydroxyethylamines (HEAs) bearing a tricyclic nonprime side. These derivatives have nanomolar cell potency and are orally bioavailable.
MeSH terms
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Administration, Oral
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Animals
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Benzothiadiazines / chemical synthesis*
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Benzothiadiazines / pharmacokinetics
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Benzothiadiazines / pharmacology
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Biological Availability
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Cyclic S-Oxides / chemical synthesis*
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Cyclic S-Oxides / pharmacokinetics
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Cyclic S-Oxides / pharmacology
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Dogs
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Ethylamines / chemical synthesis*
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Ethylamines / pharmacokinetics
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Ethylamines / pharmacology
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Models, Molecular
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Rats
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Structure-Activity Relationship
Substances
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Benzothiadiazines
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Cyclic S-Oxides
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Ethylamines
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N-(1-benzyl-3-(cyclopropylamino)-2-hydroxypropyl)-7-ethyl-1-methyl-3,4-dihydro-1H-(1,2,5)thiadiazepino(3,4,5-hi)indole-9-carboxamide 2,2-dioxide
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Amyloid Precursor Protein Secretases