Issue 7, 2012

De novo design, synthesis and pharmacological evaluation of new azaindole derivatives as dual inhibitors of Abl and Src kinases

Abstract

A new fragment based drug design approach implemented in our MedChem-Decision platform led to the discovery of a new series of 2,5 disubstituted 7-azaindole derivatives as potent dual Abl and Src kinase inhibitors. Extensive structure–activity relationships and structure-based drug design studies guided the exploration of the specificity pocket within the active conformation of the ATP site of the two kinases. This led to (1) the identification of a new binding mode of the 7-azaindole core to the two kinases and (2) the synthesis and pharmacological evaluation of compounds that exhibit low nanomolar inhibition on both Abl and Src kinases as well as moderate activity on the Abl 315I mutant.

Graphical abstract: De novo design, synthesis and pharmacological evaluation of new azaindole derivatives as dual inhibitors of Abl and Src kinases

Article information

Article type
Concise Article
Submitted
28 Jan 2012
Accepted
06 May 2012
First published
19 Jun 2012

Med. Chem. Commun., 2012,3, 788-800

De novo design, synthesis and pharmacological evaluation of new azaindole derivatives as dual inhibitors of Abl and Src kinases

G. Chevé, C. Bories, B. Fauvel, F. Picot, A. Tible, B. Daydé-Cazals, O. Loget and A. Yasri, Med. Chem. Commun., 2012, 3, 788 DOI: 10.1039/C2MD20104F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Spotlight

Advertisements