Title of article :
3-Amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: A new class of CDK2 inhibitors
Author/Authors :
Paolo Pevarello، نويسنده , , Daniele Fancelli، نويسنده , , Anna Vulpetti، نويسنده , , Raffaella Amici، نويسنده , , Manuela Villa، نويسنده , , Valeria Pittalà، نويسنده , , Paola Vianello، نويسنده , , Alexander Cameron، نويسنده , , Marina Ciomei، نويسنده , , Ciro Mercurio، نويسنده , , James R. Bischoff، نويسنده , , Fulvia Roletto، نويسنده , , Mario Varasi، نويسنده , , Maria Gabriella Brasca، نويسنده ,
Abstract :
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.
Keywords :
Tumor cell proliferation inhibition , Kinase selectivity , CDK2 , cyclins
