BACE-1 inhibitors part 2: Identification of hydroxy ethylamines (HEAs) with reduced peptidic character

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• 作者：Brian Clarke ; Emmanuel Demont ; Colin Dingwall ; Rachel Dunsdon ; Andrew Faller ; Julie Hawkins ; Ishrut Hussain ; David MacPherson ; Graham Maile ; Rosalie Matico ; Peter Milner ; Julie Mosley ; Alan Naylor ; Al
• 关键词：Alzheimer ; BACE-1 ; Aspartic protease ; Hydroxy ethylamine
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2008
• 出版时间：1 February 2008
• 年：2008
• 卷：18
• 期：3
• 页码：1017-1021
• 全文大小：413 K

文摘

This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the and substituents, two different binding modes were observed in X-ray co-crystal structures.