Abstract
We describe synthesis and evaluation of a series of cyclic urea derivatives with hydroxylethylamine isostere. Modification of P3, P1, and P2' and combination of SAR display a >100-fold increase in potency with good cellular activity (IC(50)=0.15microM) relative to the previously reported compound 3.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Cell Line
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Crystallography, X-Ray
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Cyclization
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Ethylamines / chemical synthesis
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Ethylamines / pharmacology*
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Humans
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Hydroxylation
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Inhibitory Concentration 50
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / pharmacology*
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Structure-Activity Relationship
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Urea / analogs & derivatives
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Urea / chemical synthesis
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Urea / pharmacology*
Substances
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Ethylamines
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Protease Inhibitors
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Urea
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases
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BACE1 protein, human