Abstract
A novel class of pyridinyl aminohydantoins was designed and prepared as highly potent BACE1 inhibitors. Compound (S)- 4g showed excellent potency with IC 50 of 20 nM for BACE1. X-ray crystallography indicated that the interaction between pyridine nitrogen and the tryptophan Trp76 was a key feature in the S2′ region of the enzyme that contributed to increased potency.
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