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We previously reported potent BACE1 inhibitors KMI-420 and KMI-570 possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Acidic moieties at the P1′ and P 4 positions of KMI inhibitors are thought to be unfavorable in terms of membrane permeability across the blood–brain barrier. Herein, we replaced acidic moieties at the P 4 position with hydrogen bond...
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