In order to obtain new molecular structure of antitumor drugs, nine heterocyclic amide compounds (Ⅱa ~ Ⅱi) were synthesized by using natural product isopimaric acid as the parent structure. The structures of target compouds were confirmed by FTIR, 1H NMR, 13C NMR and TOF-MS. The anti-tumor activity test results revealed that all target compounds showed higher anti-tumor activities than the parent compound isopimaric acid. Especilly, the compound Ⅱd containing pyrazine heterocycles showed significant cell proliferation inhibitory activity against A375 cells, and its IC50 value was 13.34 μmol / L. It is expected to become an anti-tumor lead compound of isopimaric acid by further structural modification to improve its activity.