Imperial College of Science, Technology and Medicine

Sterix Limited

Barry Victor Potter

Michael John Reed

A non-steroidal compound suitable for use as an inhibitor of oestrone sulphatase. The compound has a polycyclic ring structure comprising two or more rings wherein at least two of the rings mimic the A and B rings of oestrone. The compound can have the general formula A wherein R,-R,are independently selected from H, halo, hydroxy, sulphamate, alkyl and substituted variants or salts thereof; but wherein at least one of R,-R,is a sulphamate group; and wherein X is any one of O, S, NH, a substituted N, CH,or a substituted C.

Non-steroidal polycyclic ring sulphamate derivatives, their preparation and their use as oestrone sulphatase inhibitors

Steroid sulphatase inhibitors

A method of inhibiting steroid sulphatase activity in a subject in need of same is described. The method comprises administering to said subject a steroid sulphatase inhibiting amount of a ring system compound; which ring system compound comprises a ring to which is attached a sulphamate group of the formula ##STR1## wherein each of R.sub.1 and R.sub.2 is independently selected from H, alkyl, alkenyl, cycloalkyl and aryl, or together represent alkylene optionally containing one or more hetero atoms or groups in the alkylene chain; and wherein said compound is an inhibitor of an enzyme having steroid sulphatase activity (E.C.3.1.6.2); and if the sulphamate group of said compound is replaced with a sulphate group to form a sulphate compound and incubated with a steroid sulphatase enzyme (E.C.3.1.6.2) at a pH 7.4 and 37.degree. C. it would provide a K.sub.m value of less than 50 .mu.M.

Compounds with a sulfamate group

Phosphate esters of formula: ##STR1## for use in the inhibition of steroid sulfatase enzyme, wherein R is as defined in the specification and the -O-polycycle represents a residue of a sterol.

Steroid sulphatase inhibitors and pharmaceutical compositions containing them for use in the treatment of oestrone dependent tumors, especially breast cancer. The steroid sulphatase inhibitors are phosphonate esters of formula (I) ##STR1## where R is alkyl, alkenyl, cycloalkyl or aryl; and --O--polycycle represents the residue of a polycyclic alcohol such as a sterol, preferably a 3-sterol.

Steroid sulphatase inhibitors and pharmaceutical compositions containing them for use in the treatment of oestrone dependent tumors, especially breast cancer. The steroid sulphatase are sulphamate esters of formula (I): ##STR1## where R.sub.1 and R.sub.2 are each H, alkyl, alkenyl, cycloalkyl or aryl, or together represent an alkylene group optionally containing a heteroatom e.g. --O-- or --NH--; and --O- polycycle represents the residue of a polycyclic alcohol such as a sterol, preferably a 3-sterol.

Growing community of inventors

Bath, United Kingdom

Barry Victor Potter