Synthesis and pharmacological evaluations of novel 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives as a new class of anti-cancer agents

The synthesis of novel 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives has been carried out using trifluoroacetic anhydride/phosphoric acid mediated C–C bond forming reaction as a key step. This method does not require the use of environmentally harmful AlCl3 or moisture sensitive acid chloride. A number of compounds containing the benzooxazinone moiety attached to a five-membered central heterocyclic ring was synthesized and tested for their anti-cancer properties in vitro against three cell lines e.g. A549 (lung), DLD-1 (colorectal adenocarcinoma) and MV4-11 (acute myeloid leukemia). Some of them showed anti-cancer activities along with a number of reference compounds tested. Few of them showed promising anti-leukemic properties. A brief Structure–Activity-Relationship study within the series is presented. An imidazole derivative 9c containing benzene ring with a para-CF3 group at C-2 position was identified as a potent anti-leukemic agent.

Graphical abstractNovel 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives have been identified as a new class of anti-cancer agents of which an imidazole derivative was found to be a potent anti-leukemic agent.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 2H-Benzo[b][1,4]oxazin-3(4H)-ones has been identified as new anti-cancer agents. ► Their syntheses involve TFAA/H3PO4 mediated C–C bond forming reaction. ► These compounds showed anti-proliferative properties against three cell lines. ► An imidazole derivative was identified as a potent anti-leukemic agent.