Design and synthesis of pyrimido(4,5-b)(1,4)benzothiazine derivatives, as potent 15-lipoxygenase inhibitors.

摘要

A group of 2-substituted pyrimido[4,5-b][1,4]benzothiazines were designed, synthesized, and evaluated as potential inhibitors of 15-lipoxygenase (15-LO). Compounds 4d and 4e showed the best IC(50) of 15-LO inhibition (IC(50)=18 and 34muM, respectively). All compounds were docked into 15-LO. As a result the sulfur atom was oriented toward the iron atom of the active site of 15-LO. We suggest the interaction of the iron atom is essential for the activity of the inhibitors.