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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Synthesis of (3S,4S)-4-aminopyrrolidine-3-ol derivatives and biological evaluation for their BACE1 inhibitory activities.
Bioorganic & Medicinal Chemistry Letters 2016 January 2
Synthesis, SAR study and BACE1 inhibitory activity of (3S,4S)-4-aminopyrrolidine-3-ol derivatives (2) were described. The compound 7c exhibited more inhibition activity than 11a (IC50: 0.05μM vs 0.12μM, respectively), but the latter was more effective in cell-based assay (IC50: 1.7μM vs 40% inhibition by 7c @ 10μM) due to the relatively higher cell permeability. Most of the compounds showed high selectivity over BACE2 and cathepsin D. This work will provide useful information for further structural modifications to develop potent BACE1 inhibitors in cell.
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