Discovery of oxadiazoyl tertiary carbinamine inhibitors of β-secretase (BACE-1)

被引：76

作者：

Rajapakse, Hemaka A.

Nantermet, Philippe G.

Selnick, Harold G.

Munshi, Sanjeev

McGaughey, Georgia B.

Lindsley, Stacey R.

Young, Mary Beth

Lai, Ming-Tain

Espeseth, Amy S.

Shi, Xiao-Ping

Colussi, Dennis

Pietrak, Beth

Crouthamel, Ming-Chih

Tugusheva, Katherine

Huang, Qian

Xu, Min

Simon, Adam J.

Kuo, Lawrence

Hazuda, Daria J.

Graham, Samuel

Vacca, Joseph P.

机构：

[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA

[2] Merck Res Labs, Dept Biol Struct, West Point, PA 19486 USA

[3] Merck Res Labs, Dept Mol Syst, West Point, PA 19486 USA

[4] Merck Res Labs, Dept Alzheimers Res, West Point, PA 19486 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 25期

关键词：

D O I：

10.1021/jm061046r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：7270 / 7273

页数：4

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