Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization

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• 作者：Jared Cumming ; Suresh Babu ; Ying Huang ; Carolyn Carrol ; Xia Chen ; Leonard Favreau ; William Greenlee ; Tao Guo ; Matthew Kennedy ; Reshma Kuvelkar ; Thuy Le ; Guoqing Li ; Nansie McHugh ; Peter Orth ; Lynne Oz
• 关键词：Alzheimer’ ; s disease ; β ; -Secretase ; BACE ; Aspartyl protease inhibitors ; Peptidomimetics
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：1 May 2010
• 年：2010
• 卷：20
• 期：9
• 页码：2837-2842
• 全文大小：2391 K

文摘

With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2′ sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Aβ₄₀ in transgenic mice with a single subcutaneous dose.