3-Amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: A new class of CDK2 inhibitors

We have recently reported about a new class of Aurora-A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. Here we describe the synthesis and early expansion of CDK2/cyclin A–E inhibitors belonging to the same chemical class. Synthesis of the compounds was accomplished using a solution-phase protocol amenable to rapid parallel expansion. Compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit CDK2-mediated tumor cell proliferation have been obtained.

Graphical abstractWe recently reported about the synthesis, expansion, and biological characterization of a new bicyclic scaffold toward potent Aurora-A kinase inhibitors. Here we report the expansion of the same class with the aim of achieving potent and selective CDK inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide