Abstract
Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Animals
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Crystallography, X-Ray
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Disease Models, Animal
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Drug Design*
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Humans
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Imidazolidines / chemical synthesis*
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Imidazolidines / chemistry
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Imidazolidines / pharmacology*
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Mice
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Mice, Transgenic
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Models, Molecular
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Molecular Conformation
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Molecular Structure
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / pharmacology*
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Structure-Activity Relationship
Substances
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Imidazolidines
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Piperazines
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ethylene urea
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases
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BACE1 protein, human