New N-1,N-10-bridged pyrrolo[2,3-a]carbazole-3-carbaldehydes: Synthesis and biological activities

• New pyrrolo[2,3-a]carbazoles were synthesized.
• Inhibitory potencies were determined toward Pim kinases (Pim-1, Pim-2 and Pim-3).
• High inhibitory potencies were found toward Pim-1 and Pim-3.
• Two potent Pim inhibitors exhibited apoptosis–inducing activity toward IPC-81 cells.

The synthesis of new pyrrolocarbazoles substituted at N-1/N-10 positions is described. All the compounds tested demonstrated moderate to high Pim-1/Pim-3 kinase inhibitory potency. The most active inhibitors identified in this series (3, 17) have an alkyl chain bridging the N-1 and N-10 positions. These compounds (3, 17) exhibited apoptosis–inducing activity toward acute myeloid leukemia IPC-81 cells, but not toward normal fibroblasts.

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