Enantiomerically pure 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists

被引：29

作者：

Marugan, Juan Jose ^{[1
]}

Leonard, Kristi ^{[1
]}

Raboisson, Pierre ^{[1
]}

Gushue, Joan M. ^{[1
]}

Calvo, Raul ^{[1
]}

Koblish, Holly K. ^{[1
]}

Lattanze, Jennifer ^{[1
]}

Zhao, Shuyuan ^{[1
]}

Cummings, Maxwell D. ^{[1
]}

Player, Mark R. ^{[1
]}

Schubert, Carsten ^{[1
]}

Maroney, Anna C. ^{[1
]}

Lu, Tianbao ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev LLC, Drug Discovery, Exton, PA 19341 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 12期

关键词：

Hdm2; protein-protein interaction; p53;

D O I：

10.1016/j.bmcl.2006.03.067

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The 1,4-benzodiazepine-2,5-dione is a suitable template to disrupt the interaction between p53 and Hdm2. The development of an enantioselective synthesis disclosed the stereochemistry of the active enantiomer. An in vitro p53 peptide displacement assay identified active compounds. These activities were confirmed in several cell-based assays including induction of the p53 regulated gene (PIG-3) and caspase activity. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：3115 / 3120

页数：6

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