Discovery and SAR of spirochromane Akt inhibitors

被引：40

作者：

Kallan, Nicholas C. ^{[1
]}

Spencer, Keith L. ^{[1
]}

Blake, James F. ^{[1
]}

Xu, Rui ^{[1
]}

Heizer, Justin ^{[1
]}

Bencsik, Josef R. ^{[1
]}

Mitchell, Ian S. ^{[1
]}

Gloor, Susan L. ^{[1
]}

Martinson, Matthew ^{[1
]}

Risom, Tyler ^{[1
]}

Gross, Stefan D. ^{[1
]}

Morales, Tony H. ^{[1
]}

Wu, Wen-I ^{[1
]}

Vigers, Guy P. A. ^{[1
]}

Brandhuber, Barbara J. ^{[1
]}

Skelton, Nicholas J. ^{[2
]}

机构：

[1] Array BioPharma Inc, Boulder, CO 80301 USA

[2] Genentech Inc, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 08期

关键词：

Akt kinase inhibitors; PI3K/AKT PATHWAY; PROTEIN-KINASES; RECENT PROGRESS; PROSTATE; TARGET;

D O I：

10.1016/j.bmcl.2011.02.073

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of spirochromane pan-Akt inhibitors is reported. SAR optimization furnished compounds with improved enzyme potencies and excellent selectivity over the related AGC kinase PKA. Attempted replacement of the phenol hinge binder provided compounds with excellent Akt enzyme and cell activities but greatly diminished selectivity over PKA. (C) 2011 Elsevier Ltd. All rights reserved.

引用

收藏

页码：2410 / 2414

页数：5

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