Synthesis of a novel series of chromen-3-yl-pyridine moieties. IR, NMR, and MS spectroscopy were used to confirm the structure of these novel compounds and study of antitumor activity of these compounds. The structure activity relationship investigation demonstrated that 2,4-diamino-5-(3-methoxyphenyl)-7-(2-oxo-2H-chromen-3-yl)-1,8-naphthyridine-3-carbonitrile (16), was more effective and naphthyridine-3-carbonitrile derivatives 17, 18 and pyrido[2,3-d]pyrimidine derivative 12, while compounds 5a,b, 9c, 11, 13 and 14 were moderate activity for antitumor activities.