Pyrrolidinyl pyridone and pyrazinone analogues as potent inhibitors of prolyl oligopeptidase (POP)

被引：48

作者：

Haffner, Curt D. ^{[1
]}

Diaz, Caroline J. ^{[1
]}

Miller, Aaron B. ^{[2
]}

Reid, Robert A. ^{[2
]}

Madauss, Kevin P. ^{[2
]}

Hassell, Annie ^{[2
]}

Hanlon, Mary H. ^{[3
]}

Porter, David J. T. ^{[3
]}

Becherer, J. David ^{[3
]}

Carter, Luke H. ^{[4
]}

机构：

[1] GlaxoSmithKline Res & Dev Ltd, Dept Med Chem, Res Triangle Pk, NC 27709 USA

[2] GlaxoSmithKline Res & Dev Ltd, Dept Computat & Struct Chem, Res Triangle Pk, NC 27709 USA

[3] GlaxoSmithKline Res & Dev Ltd, Dept Biochem & Analyt Pharmacol, Res Triangle Pk, NC 27709 USA

[4] GlaxoSmithKline Res & Dev Ltd, Dept Biol Reagents & Assay Dev, Res Triangle Pk, NC 27709 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 15期

关键词：

prolyl oligopeptidase; serine protease; pyridone; pyrazinone; pyrrolidine; prolyl endopeptidase;

D O I：

10.1016/j.bmcl.2008.06.067

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the synthesis and in vitro activity of a series of novel pyrrolidinyl pyridones and pyrazinones as potent inhibitors of prolyl oligopeptidase (POP). Within this series, compound 39 was co-crystallized within the catalytic site of a human chimeric POP protein which provided a more detailed understanding of how these inhibitors interacted with the key residues within the catalytic pocket. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4360 / 4363

页数：4

共 36 条

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