Protein phosphorylation and dephosphorylation are important processes in the control of protein functions. Phosphorylation occurs on serine, threonine, and tyrosine residues and is catalyzed by protein kinases whose number transcends 800 in the human genome. Because of the importance of protein phosphorylation as a main post-translational mechanism used by cells to regulate enzymes and other proteins and the association of many maladies with its aberrations, kinases have increasingly become important targets and the hunt for kinase inhibitors has been intensified and attracted a great attention in drug discovery over the years. Cyclin dependent kinases have appeared as important drug target over the years with a multitude of therapeutic potentials. Cyclin dependent kinase 2 (CDK2) belongs to this class of protein kinases and plays a key role in the cell cycle regulation. With the intention of designing compounds with enhanced inhibitory potencies against CDK2, the 3D-QSAR CoMFA and CoMSIA study on benzodipyrazoles series is presented here.