So, novel dihydropyrano[2,3-c]pyrazole 1, 2, 7–9, and 15, pyrazolo[4′, 3′:5,6]pyrano[2,3-d]pyrimidine 3-6, pyrazolo[3,4-d]pyrimidine 12 and 13, and pyrazolo[3,4-c]pyrazole 14 derivatives were synthesized to evaluate their antitumor activity against the HEPG2 human cancer cell line; compared to erlotinib and sorafenib as reference drugs, the in vitro EGFR and VEGFR-2 inhibitory activity and the docking mode of the most potent candidates were evaluated to explain the obtained inhibitory activity. Here, KDR is linked to cancer.