Allosteric inhibitors of Akt1 and Akt2: Discovery of [1,2,4]triazolo[3,4-f][1,6]naphthyridines with potent and balanced activity

被引：57

作者：

Li, Yiwei ^{[1
]}

Liang, Jun ^{[2
]}

Siu, Tony ^{[2
]}

Hu, Essa ^{[2
]}

Rossi, Michael A. ^{[1
]}

Barnett, Stanley F. ^{[3
]}

Defeo-Jones, Deborah ^{[3
]}

Jones, Raymond E. ^{[3
]}

Robinson, Ronald G. ^{[3
]}

Leander, Karen ^{[3
]}

Huber, Hans E. ^{[3
]}

Mittal, Sachin ^{[4
]}

Cosford, Nicholas ^{[2
]}

Prasit, Peppi ^{[2
]}

机构：

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

[2] Merck & Co Inc, Merck Res Labs, Dept Med Chem, San Diego, CA 92121 USA

[3] Merck & Co Inc, Merck Res Labs, Dept Canc Res, West Point, PA 19486 USA

[4] Merck & Co Inc, Merck Res Labs, Pharmaceut Res & Dev, West Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 03期

关键词：

Akt; Inhibitors; Allosteric; Cancer; Kinase; In vivo activity; 2,3,5-TRISUBSTITUTED PYRIDINE-DERIVATIVES; DUAL AKT-1; ONCOGENE; KINASES; AKT/PKB; CANCER; DESIGN;

D O I：

10.1016/j.bmcl.2008.12.017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of [1,2,4]triazolo[3,4-f][1,6] naphthyridine allosteric dual inhibitors of Akt1 and 2 have been developed. These compounds have been shown to have potent dual Akt1 and 2 cell potency. The representative compound 13 provided potent inhibitory activity against Akt1 and 2 in vivo in a mouse model. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：834 / 836

页数：3

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