β-分泌酶1抑制剂第2部分：具有降低肽性的羟乙胺（HEA）的鉴定。
BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character.
作者信息
Clarke Brian, Demont Emmanuel, Dingwall Colin, Dunsdon Rachel, Faller Andrew, Hawkins Julie, Hussain Ishrut, MacPherson David, Maile Graham, Matico Rosalie, Milner Peter, Mosley Julie, Naylor Alan, O'Brien Alistair, Redshaw Sally, Riddell David, Rowland Paul, Soleil Virginie, Smith Kathrine J, Stanway Steven, Stemp Geoffrey, Sweitzer Sharon, Theobald Pam, Vesey David, Walter Daryl S, Ward John, Wayne Gareth
机构信息
Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom.
出版信息
Bioorg Med Chem Lett. 2008 Feb 1;18(3):1017-21. doi: 10.1016/j.bmcl.2007.12.019. Epub 2007 Dec 15.
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 P(1)(') and P(2)(') substituents, two different binding modes were observed in X-ray co-crystal structures.
本文描述了通过取代先导二酰胺2的主侧发现的非肽类、强效且选择性的β-分泌酶1（BACE-1）羟乙胺（HEA）抑制剂。确定了具有纳摩尔效力和高选择性的抑制剂。根据P(1)'和P(2)'取代基的性质，在X射线共晶体结构中观察到两种不同的结合模式。
Zotero 插件