The synthesis and SAR of 2-amino-pyrrolo[2,3-d]pyrimidines: A new class of Aurora-A kinase inhibitors

A new class of Aurora-A inhibitors have been identified based on the 2-amino-pyrrolo[2,3-d]pyrimidine scaffold. Here, we describe the synthesis and SAR of this novel series. We report compounds which exhibit nanomolar activity in the Aurora-A biochemical assay and are able to inhibit tumor cell proliferation. This study culminates in compound 30, an inhibitor with potent activity against Aurora A (IC50 = 0.008 μM), anti-proliferative activity against several tumor cell lines and induces polyploidy in H460 cells.

Graphical abstractThe synthesis of a potent Aurora-A inhibitor 32 (IC50 = 0.8 nm) is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide