Discovery of oxadiazoyl tertiary carbinamine inhibitors of β-secretase (BACE-1)
Discovery of oxadiazoyl tertiary carbinamine inhibitors of β-secretase (BACE-1)
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DOI：
10.1021/jm061046r
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发表时间：
2006-12-14
影响因子：
7.3
通讯作者：
Vacca, Joseph P.
中科院分区：
文献类型：
--
作者：
Rajapakse, Hemaka A.;Nantermet, Philippe G.;Vacca, Joseph P.
我们描述了叔胺衍生的β-分泌酶（BACE-1）抑制剂的发现和优化。这些新的非过渡态衍生的配体包含一个单一的伯胺与目标酶的催化剂相互作用。该系列的优化提供了具有与BACE-1的进化的过渡态电子等排体衍生的抑制剂相当的内在和功能效力的抑制剂。
We describe the discovery and optimization of tertiary carbinamine derived inhibitors of the enzyme beta-secretase (BACE-1). These novel non-transition-state-derived ligands incorporate a single primary amine to interact with the catalytic aspartates of the target enzyme. Optimization of this series provided inhibitors with intrinsic and functional potency comparable to evolved transition state isostere derived inhibitors of BACE-1.