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Rational Design, Synthesis, and Biological Evaluation of 7-Azaindole Derivatives as Potent Focused Multi-Targeted Kinase Inhibitors.

Abstract：

:Efforts were made to improve a series of potent dual ABL/SRC inhibitors based on a 7-azaindole core with the aim of developing compounds that demonstrate a wider activity on selected oncogenic kinases. Multi-targeted kinase inhibitors (MTKIs) were then derived, focusing on kinases involved in both angiogenesis and tumorigenesis processes. Antiproliferative activity studies using different cellular models led to the discovery of a lead candidate (6z) that combined both antiangiogenic and antitumoral effects. The activity of 6z was assessed against a panel of kinases and cell lines including solid cancers and leukemia cell models to explore its potential therapeutic applications. With its potency and selectivity for oncogenic kinases, 6z was revealed to be a focused MTKI that should have a bright future in fighting a wide range of cancers.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Daydé-Cazals B,Fauvel B,Singer M,Feneyrolles C,Bestgen B,Gassiot F,Spenlinhauer A,Warnault P,Van Hijfte N,Borjini N,Chevé G,Yasri A

doi

10.1021/acs.jmedchem.6b00087

subject

Has Abstract

pub_date

2016-04-28 00:00:00

pages

3886-905

issue

8

eissn

0022-2623

issn

1520-4804

journal_volume

59

pub_type

杂志文章

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