摘要：Starting from 4,6-dimethyl-2-oxo-(1H)-3-pyridinecarbonitrile 1 and 3-aminopyrazolopyridine 4, a series of cyanopyri- dine derivatives 3a-i, Schiff bases 5a-f, urea and thiourea derivatives 6a-b, amide derivatives 7a-h, pyridopyra- zolopy-rimidine 8a-b and pyridopyrazolotriazine 10a-b were synthesized. Activities of eleven representative compounds were evaluated against A-549 (lung), HEPG2 (liver) and HCT-116 (colon) cancer cell lines. The findings revealed that some of the synthesized compounds showed remarkable anticancer activities, especially 8b which displayed the highest activity among the tested compounds with IC50 equal to 2.9, 2.6 and 2.3 μmol. In addition to synthesis and biological activities, we present discussion about the rationale of the design and activity of the potent compound 8b using struc- ture-based modeling tools.