A series of novel pyrazolopyrimidines 2-11 have been designed and synthesized. Depending on the screening A series of novel pyrazolopyrimidines 2-11 have been designed and synthesized. Depending on the screening program of NCI, 2-11 have been estimated in vitro for their anti-proliferative properties on 60 cell line subpanels. Among them, compounds 6 and 11 displayed excellent antiproliferative effects against glioma cell line (SF-539) with GI values of 85.85% and 63.65%, respectively. Therefore, the IC50 values for compounds 6 and 11 against the SF-539 cell line were obtained with the best results, using Roscovitine as a positive control. Compound 6 showed the best inhibitory activity with IC50 value of 11.1 μM, representing 1.5-folds the potency of Roscovitine, while compound 11 exhibited 71% the inhibitory activity of the reference used. Enzymatic inhibition studies on compound 6 show that it has activity on cyclin-dependent kinase 2 (CDK2/cyclinA) with IC50 equal 0.76 μM, compared to Roscovitine (IC50 = 0.44 μM). Compound 6 was tested for toxicity against normal human lung cell line (WI-38), and it possessed no toxicity against it. Its IC50 value was found to be 66.20 μM. A docking investigation was done to disclose interactions of compounds 6 and 11 in the CDK2 kinase's active site. Computational ADME analysis was achieved to ensure that, compounds 6 and 11 have appropriate pharmacokinetic and drug-likeness characteristics.