Abstract
Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date.
Publication types
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Research Support, Non-U.S. Gov't
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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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Amyloid Precursor Protein Secretases / chemistry
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Amyloid Precursor Protein Secretases / metabolism
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Aspartic Acid Endopeptidases / chemistry
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Aspartic Acid Endopeptidases / metabolism
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Cell Line
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Crystallography, X-Ray
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Humans
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Hydrogen Bonding
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Models, Molecular
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Piperidines / chemical synthesis
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Piperidines / chemistry*
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Piperidines / pharmacology*
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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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Pyrrolidines / chemical synthesis
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Pyrrolidines / chemistry*
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Pyrrolidines / pharmacology*
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Structure-Activity Relationship
Substances
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Piperidines
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Protease Inhibitors
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Pyrrolidines
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases
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BACE1 protein, human
Associated data
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PDB/2QK5
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PDB/2QMD
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PDB/2QMF
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PDB/2QP8