The design, synthesis and in vitro biological evaluation of isothiochroman 2, 2-dioxide and 1, 2-benzooxathiin 2, 2-dioxide analogues of coumarin inhibitors of gyrase B are described. Compared to coumarin derivatives, compounds of the 1, 2-benzooxathiin 2, 2-dioxide series display improved inhibitory potency in negative supercoiling of relaxed DNA gyrase.