Synthesis and molecular modelling of novel 8-aryl and 7,8-substituted-2-morpholino-1,3-benzoxazines

DNA-dependent protein kinase (DNA-PK) is a key enzyme in the process of DNA repair, one of the key limiting factors to effective chemotherapy, causing drug resistance in a range of cancers. DNA-PK is a prominent target as a potential combination therapy with existing anti-cancer drugs, such as etoposide and doxorubicin. DNA-PK is structurally homologous to another signalling enzyme PI3K kinase, which promotes cell survival and proliferation and is up-regulated in many cancers. Dual DNA-PK and PI3K inhibitors are a promising class of potential therapeutic. We aim to synthesize and evaluate a library of 8-aryl-2-morpholino-1,3-benzoxazines that show these activities.