Synthesis of new dipyrrolo- and furopyrrolopyrazinones related to tripentones and their biological evaluation as potential kinases (CDKs1–5, GSK-3) inhibitors

We herein describe the synthesis of novel dipyrrolo- and furopyrrolopyrazinones related to highly cytotoxic tripentones and to their oximes. The synthetic pathway involved in particular a Curtius rearrangement and a subsequent cyclisation into the title pyrazinones. The biological evaluation towards various cyclin-dependent kinases (CDKs1–5, GSK-3) highlighted a weak inhibitory activity for the oximes whose SAR was studied by a molecular modeling study.

Graphical abstractA series of new dipyrrolo- and furopyrrolopyrazinones related to cytotoxic tripentones were synthesized and evaluated as potential (CDKs1–5, GSK-3) kinase inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide