Synthesis and biological evaluation of substituted 3-anilino-quinolin-2(1H)-ones as PDK1 inhibitors

被引：20

作者：

O'Brien, Nathan J. ^{[1
]}

Brzozowski, Martin ^{[1
]}

Wilson, David J. D. ^{[1
]}

Deady, Leslie W. ^{[1
]}

Abbott, Belinda M. ^{[1
]}

机构：

[1] La Trobe Univ, La Trobe Inst Mol Sci, Dept Chem, Bundoora, Vic 3086, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 14期

关键词：

3-Phosphoinositide-dependent kinase 1 (PDK1); 3-Anilino-quinolin-2(1H)-ones; Inhibitor; Buchwald-Hartwig cross-coupling; Cross-coupling; SMALL-MOLECULE INHIBITORS; EFFICIENT SYNTHESIS; DERIVATIVES; KINASE; POTENT; PATHWAY; DESIGN; IDENTIFICATION; PKB/AKT; ANALOGS;

D O I：

10.1016/j.bmc.2014.04.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

PDK1 is an important regulator of the PI3K/Akt pathway, which has been found frequently activated in a large number of human cancers. Herein we described the preparation of novel substituted 3-anilino-quinolin-2(1H)-ones as PDK1 inhibitors. The synthesis is based around a Buchwald-Hartwig cross-coupling of various 3-bromo-6-substituted-quinolin-2(1H)-ones with three different functionalised anilines. The modular nature of the designed synthesis allowed access to a series of novel inhibitors through derivatisation of a late-stage intermediate. All compounds were screened against isolated PDK1 enzyme, with modest inhibition observed. Crown Copyright (C) 2014 Published by Elsevier Ltd. All rights reserved.

引用

页码：3781 / 3790

页数：10

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