Synthesis and biological evaluation of selected 7-azaindole derivatives as CDK9/Cyclin T and Haspin inhibitors

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Pieterse, Lianie | Legoabe, Lesetja, J | Beteck, Richard, M | Josselin, Béatrice | Bach, Stéphane | Ruchaud, Sandrine

Edité par CCSD ; Springer Verlag -

International audience. The 7-azaindole scaffold attracts attention due to its value in the design of inhibitors of diseases related protein kinases. However, this scaffold has not been evaluated against Haploid germ cell-specific nuclear protein kinase (Haspin). Herein, we report the synthesis of a select set of 7-azaindole derivatives and their evaluation against Haspin. The compounds were also evaluated against CDK9/Cyclin T kinase. The synthesis of 7-azaindole derivatives was achieved through Suzuki coupling using appropriate halogenated 7-azaindole and boronic acids. Seven of the screened compounds exhibited activity as CDK9/Cyclin T and/or Haspin inhibitors in a nanomolar to low micromolar range. The most promising dual inhibiting compound 18c, exhibited an inhibitory potential of 0.206 µM against CDK9/Cyclin T and 0.118 µM against Haspin. The dual inhibition of CDK9/Cyclin T and Haspin could afford a potentially potent antimitotic agent of value in further anticancer studies.

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