Use of Copper(I) Catalyzed Azide Alkyne Cycloaddition (CuAAC) for the preparation of conjugated pyrrolo[2,3-a]carbazole Pim kinase inhibitors
Résumé
We have previously demonstrated that pyrrolo[2,3-a ]carbazole-3-carbaldehydes are potent Pim kinase inhibitors with in vitro antiproliferative activities. In the present study, we report the synthesis of new pyrrolocarbazoles substituted at the N-10 position. When their ability to inhibit Pim kinase activities were evaluated in in vitro assays, we observed that this nitrogen atom can be substituted without loss of Pim-1 and Pim-3 inhibitory potencies. Moreover, when we added afl uorescent dansyl group (compound13), we were able to show that 13penetrates the plasma membrane and enters the cytoplasm.