Synthesis and biological activities of 4-substituted pyrrolo[2,3-a]carbazole Pim kinase inhibitors

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 and biological activities (Pim kinase inhibition and in vitro antiproliferative potency) of new 4-substituted pyrrolo[2,3-a]carbazoles. The results demonstrated that the Pim kinase inhibitory potency (especially Pim-3) can be conserved for pyrrolo[2,3-a]carbazoles bearing a methoxycarbonyl group at the 4-position without a formyl at the 3-position. Moreover, compound 27 that was found to be active against Pim-1 and Pim-3 kinases showed antiproliferative activities in the micromolar range.

New 4-substituted pyrrolo[2,3-a]carbazoles were synthesized and evaluated for their Pim kinase inhibitory potencies and their in vitro antiproliferative activities.Figure optionsDownload as PowerPoint slideHighlights
► New 4-substituted pyrrolo[2,3-a]carbazoles were synthesized.
► We evaluated Pim kinase inhibitory potency of 4-substituted pyrrolo[2,3-a]carbazoles.
► Methyl esters are more active toward Pim kinases than their carboxylic acid analogs.
► A putative binding mode between compound 27 and Pim-3 was proposed.