First report of the investigation into the importance of pKa in the inhibition of estrone sulfatase by sulfamate containing compounds

In an effort to rationalise the inhibitory activity of a range of aminosulfamate compounds and to further investigate the recently reported definitive pharmacophore estrone sulfatase (ES), we undertook extensive synthesis, biochemical evaluation and physicochemical property determination of a range of similar compounds. Here, we report the initial results of our study into a series of simple (aminosulfonate based) substituted phenol derivatives, Using these compounds, we investigated the role of pK(a) in the inhibition of ES, The results of the study suggest that there is a strong correlation between the inhibitory activity and the stability of the resulting O- anion (i.e., the pK(a) of the starting phenol), (C) 2000 Academic Press.