AbstractOestrone 3‐O‐sulphamate, wherein a sulphamate moiety is a sulphate group surrogate relative to oestrone sulphate, is the most potent oestrone sulphatase inhibitor developed to date and inhibits oestrone sulphatase in a time‐ and concentration‐dependent manner, showing that it is acting as an active site‐directed irreversible inhibitor. It also inhibits dehydroepiandrosterone sulphatase, the enzyme which regulates the synthesis of androstenediol. Oestrone 3‐O‐sulphamate has also been shown to inhibit these enzymes in‐vivo. We report here its crystal structure and the synthesis and inhibitory activites of analogues in which the 3‐O atom is replaced by other heteroatoms (N and S).Oestrone 3‐N‐sulphamate and oestrone 3‐S‐sulphamate were found to inhibit placental microsome oestrone sulphatase weakly, i.e. 53% and 12%, respectively, at 50 μM (compared with>99% for oestrone 3‐O‐sulphamate), but none of these compounds appears to behave