Steroid 3-O-sulphamate derivatives as inhibitors of oestrone sulphatase

Abstract

A sulphamate compound suitable for use as an inhibitor of oestrone sulphatase (E.C.3.1.6.2) is described. The compound is a polycyclic compound comprising at least two ring components, wherein the polycyclic compound comprises at least one sulphamate group attached to at least one of the ring components, and wherein at least one of the ring components of the polycyclic structure is a heterocyclic ring.

1 . A sulpharmate compound suitable for use as an inhibitor of oestrone sulphatase (E.C. 3.1.6.2), wherein the compound is a polycyclic compound comprising at least two ring components, wherein the polycyclic compound comprises at least one sulphamate group attached to at least one of the ring components, and wherein at least one of the ring components of the polycyclic structure is a heterocyclic ring.  
     
     
         2 . A sulphamate compound according to  claim 1  wherein the polycyclic compound has a steroidal structure but wherein the D ring is a heterocyclic ring.  
     
     
         3 . A sulphamate compound according to  claim 1  or  claim 2  wherein the heterocyclic ring is a six membered heterocyclic ring.  
     
     
         4 . A sulphamate compound according to any one of the preceding claims wherein the heterocylic ring is or comprises a lactone or a lactam.  
     
     
         5 . A sulphamate compound according to any one of the preceding claims wherein the polycyclic compound has a steroidal structure and wherein the sulphamate group is attached to the A ring.  
     
     
         6 . A sulphamate compound according to  claim 5  wherein the sulphamate group is attached to the 3 position of the A ring.  
     
     
         7 . A sulphamate compound suitable for use as an inhibitor of oestrone sulphatase (E.C. 3.1.6.2), comprising the formula:  
       
         
           
           
               
               
           
         
       
       wherein R is a sulphamate group and D 1  represents a heterocyclic ring and/or a six membered ring.  
     
     
         8 . A sulphamate compound according to any one of the preceding claims wherein the sulphamate group has the formula:  
       
         
           
           
               
               
           
         
       
       wherein each of R 1  and R 2  is independently selected from H or a hydrocarbyl group.  
     
     
         9 . A sulphamate compound according to any one of the preceding claims wherein the compound is not hydrolysable by an enzyme having steroid sulphatase activity.  
     
     
         10 . A pharmaceutical composition comprising a sulphamate compound according to any one of the preceding claims admixed with a pharmaceutically acceptable diluent, carrier or excipient.  
     
     
         11 . Use of a sulphamate compound according to any one of  claims 1  to  10  in the manufacture of a medicament to inhibit steroid sulphatase activity.  
     
     
         12 . A method of treatment comprising treating a subject with a sulphamate compound according to any one preceding  claims 1  to  9  or a composition according to  claim 10  and in an amount such that at least some steroid sulphatase inhibition occurs within the subject.  
     
     
         13 . A process for preparing a sulphamate compound according to any one of  claims 1  to  9  comprising a sulphamylation step.  
     
     
         14 . A sulphamate compound substantially as described herein.