BACE-1 inhibitors part 3: Identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells
详细信息 查看全文
- 作者：Paul Beswick ; Nicolas Charrier ; Brian Clarke ; Emmanuel Demont ; Colin Dingwall ; Rachel Dunsdon ; Andrew Faller ; Robert Gleave ; Julie Hawkins ; Ishrut Hussain ; Christopher N. Johnson ; David MacPherson ; Gr
- 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：1022-1026
- 全文大小：226 K
文摘
This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays.