Thiophene substituted acylguanidines as BACE1 inhibitors
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- 作者：William F. Fobare ; William R. Solvibile ; Albert J. Robichaud ; Michael S. Malamas ; Eric Manas ; Jim Turner ; Yun Hu ; Erik Wagner ; Rajiv Chopra ; Rebecca Cowling ; Guixan Jin ; Jonathan Bard
- 关键词：Beta-secretase ; BACE1 ; Aspartyl protease ; Acylguanidine
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2007
- 出版时间：1 October 2007
- 年：2007
- 卷：17
- 期：19
- 页码：5353-5356
- 全文大小：341 K
文摘
A series of thiophene-substituted acylguanidines were designed from a pyrrole substituted acylguanidine HTS lead. This template allowed a greater flexibility, through differential Suzuki couplings, to explore the binding site of BACE1 and to enhance the inhibitory potencies. This exploration provided a 25-fold enhancement in potency to yield compound 10a, which was 150 nM in a BACE1 FRET assay.