Title

Synthesis and Biological Evaluation of Substituted 3-anilino-quinolin-2(1H)-ones as PDK1 Inhibitors

Author Faculty (Discipline)

Science

Document Type

Article

Publication Date

7-15-2014

Early Online Version

5-9-2014

Journal

Bioorganic and Medicinal Chemistry

Volume Number

22

Issue Number

14

Page Numbers

3781-3790

ISSN

0968-0896

Embargo Period

3-23-2015

ANZSRC / FoR Code

030701 Quantum Chemistry

Peer Review

Before publication

Abstract

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.

Link to publisher version (DOI)

https://doi.org/10.1016/j.bmc.2014.04.037

Comments

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Copyright © 2014 Published by Elsevier Ltd. All rights reserved.

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