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

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

  • J Med Chem. 2016 Apr 28;59(8):3886-905. doi: 10.1021/acs.jmedchem.6b00087.
Bénédicte Daydé-Cazals 1 Bénédicte Fauvel 1 Mathilde Singer 1 Clémence Feneyrolles 1 Benoit Bestgen 1 Fanny Gassiot 1 Aurélia Spenlinhauer 1 Pierre Warnault 1 Nathalie Van Hijfte 1 Nozha Borjini 1 Gwénaël Chevé 1 Abdelaziz Yasri 1
Affiliations

Affiliation

  • 1 OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
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.

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