C(14) estrogenic compounds

• US 6,992,075 B2
• Filed: 04/04/2003
• Issued: 01/31/2006
• Est. Priority Date: 04/04/2003
• Status: Expired due to Fees

• Current Assignee: Barr Laboratories Incorporated (Teva Pharmaceutical Industries Limited)
• Original Assignee: Barr Laboratories Incorporated (Teva Pharmaceutical Industries Limited)
• Inventors: Leonard, Thomas W., Hill, Edward N., Whittle, Robert R.
• Primary Examiner(s): Badio, Barbara P.
• Application Number:
  US10/407,509
• Publication Number:
  US 20040198670A1
• Time in Patent Office: 1,033 Days
• Field of Search: 552/618, 514/179, 514/182
• US Class Current: 514/179
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: C07J 31/006 not covered by C07J31/003

Abstract

The present invention relates to novel estrogenic compounds. The present invention also relates to methods of treating estrogen deprivation in a subject comprising administering novel estrogenic compounds. Additionally, the present invention relates to methods of synthesizing novel estrogenic compounds.

Claims

1. A compound comprising the formula

wherein R₁ is selected from the group consisting of peroxy, hydroxy, halogen, ester, glucuronide, sulfate, phosphate, pyrophosphate and thiol, or a pharmaceutically acceptable salt thereof;

R₂ is selected from the group of glucuronide, sulfate, phosphate and pyrophosphate;

and R₃ is selected from the group consisting of hydroxy, ester, glucoronide, sulfate, phosphate and ketone.

2. The compound of claim 1, wherein said compound is:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1, wherein said compound is:

or a pharmaceutically acceptable salt thereof.

4. A method of treating a subject for estrogen deprivation comprising administering a compound comprising the formula:

wherein R₁ is selected from the group consisting of peroxy, hydroxy, halogen, and thiol, or a pharmaceutically acceptable salt thereof; and

R₂ is selected from the group consisting of hydroxy, ester, glucoronide, sulfate, phosphate and ketone.

5. The method according to claim 4, wherein said compound is 14-hydroxy-Δ

^8,9-Dehydroestrone Sodium Sulfate.

6. The method according to claim 4, wherein said compound is 14-hydroperoxy-Δ

^8,9-Dehydroestrone Sodium Sulfate.

7. A method of synthesizing an estrogenic composition, said method comprising:

subjecting an estrogenic composition comprising at least one estrogenic compound to thermal energy and high humidity that promotes the generation of at least one additional estrogenic compound in a final estrogenic composition that was not present in the initial estrogenic composition.

8. The method according to claim 7, wherein the composition is maintained at a temperature between 30°

to 60°

C.

9. The method according to claim 7, wherein the composition is kept at 50% to 90% relative humidity.

10. The method according to claim 7, wherein said subjecting step is carried out from about 3 to about 72 hours.

11. The method according to claim 7, wherein the estrogenic composition comprises a conjugated estrogen selected from the group consisting of a sulfate of an estrogen, a glucuronide of an estrogen, and mixtures thereof.

12. The method according to claim 7, wherein the estrogen is selected from the group consisting of estrone, 17α

-estradiol, 17β

-estradiol, equilin, 17α

-dihydroequilin, 17β

-dihydroequilin, equilenin, 17α

-dihydroequilenin, 17β

-dihydroequilenin, Δ

^8,9-dehydroestrone, 17α

-Δ

^8,9-dehydroestradiol, 17β

-Δ

^8,9-dehydroestradiol, ethinyl estradiol, estradiol valerate, 6-OH equilenin, 6-OH 17α

-dihydroequilenin, 6-OH 17β

-dihydroequilenin, 17-β

hydroxy derivatives thereof, salts thereof, ketones thereof, and mixtures thereof.

13. The method according to claim 7, wherein the estrogenic composition comprises Δ

^8,9-dehydroestrone sulfate.