Structure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor
Structure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor
复制标题
DOI：
10.1016/j.bmcl.2012.02.013
复制
发表时间：
2012-04-01
影响因子：
2.7
通讯作者：
Stamford, Andrew W.
中科院分区：
文献类型：
--
作者：
Cumming, Jared N.;Smith, Elizabeth M.;Stamford, Andrew W.
从最初的先导1开始，基于结构的设计方法导致鉴定出一种新的，高亲和力的亚氨基乙酰托因BACE1抑制剂，在大鼠口服给药后降低cns衍生的Ab。在此，我们报道了在BACE1的S3和F'亚位上的SAR的发展，在这项工作中采用的合成方法，以及优化化合物的体内数据。(C) 2012 Elsevier Ltd.版权所有。
From an initial lead 1, a structure-based design approach led to identification of a novel, high-affinity iminohydantoin BACE1 inhibitor that lowers CNS-derived Ab following oral administration to rats. Herein we report SAR development in the S3 and F' subsites of BACE1 for this series, the synthetic approaches employed in this effort, and in vivo data for the optimized compound. (C) 2012 Elsevier Ltd. All rights reserved.