Identification of pyrrolo[2,3-g]indazoles as new Pim kinase inhibitors.
Résumé
The synthesis and Pim kinase inhibition potency of a new series of pyrrolo[2,3-g]indazole derivatives is described. The results obtained in this preliminary structure–activity relationship study pointed out that sub-micromolar Pim-1 and Pim-3 inhibitory potencies could be obtained in this series, more particularly for compounds 10 and 20, showing that pyrrolo[2,3-g]indazole scaffold could be used for the development of new potent Pim kinase inhibitors. Molecular modeling experiments were also performed to study the binding mode of these compounds in Pim-3 ATP-binding pocket.