Design and synthesis of cell potent BACE-1 inhibitors: Structure–activity relationship of P
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- 作者：Jennifer M. Sealy ; Anh P. Truong ; Luke Tso ; Gary D. Probst ; Jose Aquino ; Roy K. Hom ; Barbara M. Jagodzinska ; Darren Dressen ; David W.G. Wone ; Louis Brogley ; Varghese John ; Jay S. Tung ; Michael A. Plei
- 关键词：Alzheimer’ ; s disease ; β ; -Secretase (BACE-1) inhibitor ; Hydroxyethylamine (HEA)
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2009
- 出版时间：15 November 2009
- 年：2009
- 卷：19
- 期：22
- 页码：6386-6391
- 全文大小：1450 K
文摘
Using structure-guided design, hydroxyethylamine BACE-1 inhibitors were optimized to nanomolar Aβ cellular inhibition with selectivity against cathepsin-D. X-ray crystallography illuminated the S1′ residues critical to this effort, which culminated in compounds 56 and 57 that exhibited potency and selectivity but poor permeability and high P-gp efflux.