The enzyme oestrone sulfatase (ES) is responsible for the conversion of the stored (sulfated) form of oestrogens to the active form, namely oestrone. In our continuing quest to synthesize potent inhibitors of oestrone sulfatase and to determine the structural requirements for such inhibition, we have synthesized and evaluated several derivatives of phenyl sulfamate. We report the results of the synthesis and biochemical evaluation of a series of 3- and 4-aminosulfonated derivatives of phenol in an effort to investigate the role of the acid dissociation constant (pKa), and therefore the stability of the phenoxide ion, on the inhibitory activity of compounds against this enzyme. The results showed that there was a strong correlation between the observed pKa and inhibitory activity within the aminosulfonated compounds considered. This suggested that in the inhibition of oestrone sulfatase by these compounds, pKa was an important physicochemical property, and as such, the stability of the O− ion was a crucial factor in the inhibition, and therefore the drug design process.