Microwave-Assisted Synthesis of Pyridophenoxazinones, a Class of Antiproliferative Compounds

Microwave (MW) irradiation allows to prepare a mini-library of pyridophenoxazinone derivatives, that are crucial intermediates in the synthesis of new antiproliferative compounds, active for human lymphoma/leukemia. The optimized procedure, consisting of a continuous input power of 50 W (808C) and a reaction time of 30 min, leads in very satisfactory yields to both regioisomers 5H-pyrido[2,3a]phenoxazin-5-ones and isomeric 5H-pyrido[3,2-a]phenoxazin 5-ones, starting from readily available quinoline-5,8-dione and substituted 2-aminophenols (APhOHs). Broad functional group tolerance was observed. The availability of derivatives carrying a carboxyl group at the C-9 and C-10 positions enables the synthesis of a new family of 5Hpyridophenoxazin-5-one conjugates that were shown to exhibit good anti-cancer activity.