Steroid sulphatase inhibitors

• US 7,098,199 B2
• Filed: 02/25/2002
• Issued: 08/29/2006
• Est. Priority Date: 08/29/1991
• Status: Expired due to Fees

• Current Assignee: Sterix Limited
• Original Assignee: Sterix Limited
• Inventors: Potter, Barry Victor Lloyd, Reed, Michael John
• Primary Examiner(s): Badio, Barbara P.
• Application Number:
  US10/084,235
• Publication Number:
  US 20020128243A1
• Time in Patent Office: 1,646 Days
• Field of Search: 514/178, 514/182, 552/626
• US Class Current: 514/178
• CPC Class Codes: A61K 31/37 Coumarins, e.g. psoralen
• CPC Class Codes: C07D 311/16 substituted in position 7
• CPC Class Codes: C07D 311/30 not hydrogenated in the hetero ring, e.g. flavones
• CPC Class Codes: C07D 311/32 2,3-Dihydro derivatives, e.g. flavanones
• CPC Class Codes: C07D 311/36 not hydrogenated in the hetero ring, e.g. isoflavones
• CPC Class Codes: C07J 41/0072 the A ring of the steroid being aromatic

Abstract

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

wherein each of R₁ and R₂ 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° C. it would provide a K_m value of less than 50 μM.

Claims

1. A pharmaceutical composititon comprising a pharmaceutically acceptable carrier or diluent and a compound comprising a steroidal ring structure and a sulphamate group of the formula

2. The pharmaceutical composition of claim 1 wherein the compound is present in an amount to provide 100–

500 mg of compound per unit dose.

wherein said compound is an inhibitor of an enzyme having steroid sulphatase activity (E.C.3.1.6.2); and

wherein 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°

C. it would provide a K_m value of less than 50 μ

M.

3. The pharmaceutical composition according to claim 1, wherein the steroidal ring structure is a residue of a 3-sterol.

4. The pharmaceutical composititon according to claim 3, wherein the sterol is selected from group consisting of oestrone, dehydroepiandrosterones, substituted oestrones and substituted dehydroepiandrosterones.

5. The pharmaceutical composition according to any one of claim 1, 2, 3 or 4 wherein R₁ and R₂ are independently selected from H, or a C₁–

C₅ alkyl;

but wherein at least one of R₁ and R₂ is H.

6. The pharmaceutical composition according to claim 5 wherein R₁ and R₂ are independently selected from H, or C₁–

C₅ alkyl;

but wherein at least one of R₁ and R₂ is H.

7. The pharmaceutical composition according to claim 6 wherein R₁ and R₂ are independently selected from H or methyl;

but wherein at least one of R₁ and R₂ is H.

8. The pharmaceutical composition according to claim 5 wherein R₁ is H and R₂ is H.

9. The pharmaceutical composition according to any one of claim 1 or 2 wherein the compound is oestrone 3-sulphamate, oestrone-3-N,N-dimethylsuphamate, or oestrone-3-N-monoethylsuphamate.