Thiazolo[5,4-f]quinoxalines, Oxazolo[5,4-f]quinoxalines and Pyrazino[b,e]isatins: Synthesis from 6-Aminoquinoxalines and Properties

The regioselective iodination of different 2-mono-, 3-mono- and 2,3-disubstituted 6-aminoquinoxalines, which takes place at their 5-position, was rationalized on the basis of Huckel theory calculations. Oxazolo- and thiazolo[5,4-f]quinoxaline analogues of reported disease-related protein kinases inhibitors were synthesized from the obtained 6-amino-5-iodoquinoxalines by using as key step copper-catalyzed azole ring formation. Pyrazino[b,e]isatins were obtained, for the first time, from the same substrates by recourse to Sonogashira coupling, alkyne hydration, and oxidative cyclization. The absorption and emission properties of the most promising compounds were recorded. In addition, most of the synthesized polycycles were evaluated as protein kinase inhibitors and for their antiproliferative activity towards cancer cells.