Pyridinyl aminohydantoins as small molecule BACE1 inhibitors

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• 作者：Ping Zhou ; Yanfang Li ; Yi Fan ; Zheng Wang ; Rajiv Chopra ; Andrea Oll ; Yun Hu ; Ronald L. Magolda ; Menelas Pangalos ; Peter H. Reinhart ; M. James Turner ; Jonathan Bard ; Michael S. Malamas ; Albert J. Robi
• 关键词：Alzheimer’ ; s disease ; β ; -Secretase ; BACE1 ; Pyridinyl aminohydantoins
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：1 April 2010
• 年：2010
• 卷：20
• 期：7
• 页码：2326-2329
• 全文大小：440 K

文摘

A novel class of pyridinyl aminohydantoins was designed and prepared as highly potent BACE1 inhibitors. Compound (S)-4g showed excellent potency with IC₅₀ 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.