Discovery of benzisoxazoles as potent inhibitors of chaperone heat shock protein 90

被引：85

作者：

Gopalsamy, Ariamala ^{[1
]}

Shi, Mengxiao ^{[1
]}

Golas, Jennifer ^{[2
]}

Vogan, Erik ^{[3
]}

Jacob, Jaison ^{[3
]}

Johnson, Mark ^{[3
]}

Lee, Frederick ^{[1
]}

Nilakantan, Ramaswamy ^{[1
]}

Petersen, Roseann ^{[2
]}

Svenson, Kristin ^{[3
]}

Chopra, Rajiv ^{[3
]}

Tam, May S. ^{[3
]}

Wen, Yingxia ^{[3
]}

Ellingboe, John ^{[1
]}

Arndt, Kim ^{[2
]}

Boschelli, Frank ^{[2
]}

机构：

[1] Wyeth Ayerst Res, Chem & Screening Sci, Pearl River, NY 10965 USA

[2] Wyeth Ayerst Res, Discovery Oncol, Pearl River, NY 10965 USA

[3] Wyeth Ayerst Res, Chem & Screening Sci, Cambridge, MA 02139 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 03期

关键词：

D O I：

10.1021/jm701385c

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Heat shock protein 90 (Hsp90) is a molecular chaperone that is responsible for activating many signaling proteins and is a promising target in tumor biology. We have identified small-molecule benzisoxazole derivatives as Hsp90 inhibitors. Crystallographic studies show that these compounds bind in the ATP binding pocket interacting with the Asp93. Structure based optimization led to the identification of potent analogues, such as 13, with good biochemical profiles.

引用

页码：373 / 375

页数：3

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