Design, Synthesis, Molecular Docking and Biological Studies of 4H‐Benzo[d][1,3]oxazin‐4‐one Derivatives and Their Uses in Heterocyclic Synthesis

Abstract

2‐(4‐Oxo‐4H‐benzo[d][1,3]oxazin‐2‐yl)acetonitrile (4) was synthesized through the reaction of anthranilic acid with ethyl cyanoacetate. The reactivity of the latter product toward chemical reagents was studied to produce coumarin, ylidene, thiophene, thieno[2,3‐b]pyridine, thiazole and pyrazole derivatives. The synthesized compounds were evaluated against three cancer cell lines namely HEPG2, HONE1 and MCF and normal cell line W138. The most active compounds 4, 6, 8 b, 12, 14, 16, 18 a, 18 b, 19, 21, 23 a, 23 b, 27 a, 27 b, 29 b, 31, 33 b, 36, 38 c and 39 b were further evaluated toward c‐Met kinase inhibitions. Overall results of inhibition toward the cancer cell lines showed that most of the tested compounds have high potent effect. The obtained results of c‐Met kinase inhibitions showed that all tested compounds gave high inhibitions. The results obtained through this work encourage us for future work using benzo[d]oxazine derivatives to produce target molecules as anticancer agents. Molecular docking of compounds 4, 6 and 16 were performed.