In this study, the starting compounds, 2-cyanomethyl benzimidazoles (1 or 2) were reacted with ethyl acetoacetate, ethyl benzoylacetate, or 2-acetylbutyrolactone to give the novel series of 4-cyano-3-substituted-1 oxo-1H, 5H-pyrido[1,2-a]benzimidazole (3–6, 15, 16). The latter was chlorinated to give compounds 7–10, 17, 18 then aminated with 4-(2-fluorophenyl) piperazine to afford compounds 11–14, 19, 20. The structures of the new compounds were confirmed by elemental analysis as well as 1 H-NMR, IR, and mass data. All the synthesized products were subjected to in vitro anticancer screening that revealed that all the tested compounds exhibited antitumor activity against human breast adenocarcinoma (MCF7) cell line, with IC50's 3.43–14.70 lg/ml.