Discovery of a novel series of Notch-sparing γ-secretase inhibitors
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- 作者：Anthony Kreft ; Boyd Harrison ; Suzan Aschmies ; Kevin Atchison ; David Casebier ; Derek C. Cole ; George Diamantidis ; John Ellingboe ; Diane Hauze ; Yun Hu ; Donna Huryn ; Mei Jin ; Dennis Kubrak ; Peimin Lu ; Jo
- 关键词：Alzheimer’ ; s disease ; γ ; -Secretase ; Notch ; Amyloid ; Protease inhibitor
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 出版时间：15 July 2008
- 年：2008
- 卷：18
- 期：14
- 页码：4232-4236
- 全文大小：198 K
文摘
Using a cell-based assay, we have identified a new series of Notch-sparing γ-secretase inhibitors from HTS screening leads 2a and 2e. Lead optimization studies led to the discovery of analog 8e with improved γ-secretase inhibitory potency and Notch-sparing selectivity.