摘要：Starting from.4,6-dim.thyl-2-oxo-(1H)-3-pyridinecarbonitrile 1 and 3-am.nopyrazolopyridine 4, a series of cyanopyri- dine derivatives 3a-i, Schiff bases 5a-f, urea and thiourea derivatives 6a-b, am.de derivatives 7a-h, pyridopyra- zolopy-rim.dine 8a-b and pyridopyrazolotriazine 10a-b were synthesized. Activities of eleven representative com.ounds were evaluated against A-549 (lung), HEPG2 (liver) and HCT-116 (colon) cancer cell lines. The findings revealed that som. of the synthesized com.ounds showed rem.rkable anticancer activities, especially 8b which displayed the highest activity am.ng the tested com.ounds with IC50 equal to 2.9, 2.6 and 2.3 μm.l. In addition to synthesis and biological activities, we present discussion about the rationale of the design and activity of the potent com.ound 8b using struc- ture-based m.deling tools.