(3) and (6) substituted estrogenic compounds

• US 7,179,799 B2
• Filed: 07/23/2003
• Issued: 02/20/2007
• Est. Priority Date: 03/10/2000
• Status: Expired due to Fees

• Current Assignee: Duramed Pharmaceuticals Incorporated (Teva Pharmaceutical Industries Limited)
• Original Assignee: Barr Laboratories Incorporated (Teva Pharmaceutical Industries Limited)
• Inventors: Hill, Edward N., Whittle, Robert R., Sancilio, Frederick D.
• Primary Examiner(s): Badio; Barbara P.
• Application Number:
  US10/628,057
• Publication Number:
  US 20040147496A1
• Time in Patent Office: 1,308 Days
• Field of Search: 552/615, 514/170, 514/171, 514/178, 514/182
• US Class Current: 514/178
• CPC Class Codes: C07J 1/00 Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane

Abstract

Novel estrogenic compounds of Formula I are provided.

wherein the bond represented by the wavy line may be a single or double bond such that when the wavy line is a single bond, R₁ is selected from the group consisting of hydrogen, sulfate and glucoronate or other esters, and when the wavy line is a double bond, R₁ does not exist; R₂ is lower alkyl; R₃ may be selected from the group consisting of hydrogen, sulfate, or glucuronide or other esters; and R₄ through R₁₃ may independently be selected from the group consisting of hydrogen, hydroxy, ketone, lower allyl, lower alkoxy, halogen, and carbonyl groups and R₁₄ is selected from the group consisting of hydrogen, sulfate and glucoronide and other esters. When R₁ is hydroxy, the hydroxy or ester substituent may have either an α or a β orientation. Compositions of matter including compounds of the present invention are also provided as are methods of treating mammals in need of treatment using compounds of the present invention.

Claims

1. A compound represented by Formula I:

2. The compound according to claim 1, wherein said compound is greater than about 95% pure.

3. The compound according to claim 1, wherein R₂ is C₁ to C₄ alkyl, R₄–

R₁₂ are hydrogen and R₁₃ is hydrogen or ethynyl.

4. The compound according to claim 1, wherein when R₁ is hydrogen, the compound has a β

orientation at the C17 position.

5. A pharmaceutical composition incorporating a compound represented by Formula I:

6. The pharmaceutical composition according to claim 5, wherein said compound is greater than about 95% pure.

7. The pharmaceutical composition according to claim 5, wherein R₂ is C₁ to C₄ alkyl, R₄–

R₁₂ are hydrogen and R₁₃ is hydrogen or ethynyl.

8. The pharmaceutical composition according to claim 5, wherein when R₁ is hydrogen, the compound has a β

orientation at the C17 position.

9. The pharmaceutical composition according to claim 5, wherein the composition further comprises at least one additional pharmaceutically active ingredient.

10. The pharmaceutical composition according to claim 9, wherein the at least one additional pharmaceutically active ingredient is selected from the group consisting of estrogenic compounds, androgenic compounds, progestin compounds, vasodilation agents, calcium salts, and vitamin D, and mixtures and combinations thereof.

11. A method of treating a subject in need of estrogen therapy, said method comprising administering an effective amount of a compound represented by Formula I:

12. The method according to claim 11, wherein said compound is greater than about 95% pure.

13. The method according to claim 11, wherein R₂ is C₁ to C₄ alkyl, R₄–

R₁₂ are hydrogen and R₁₃ is hydrogen or ethynyl.

14. The method according to claim 11, wherein when R₁ is hydrogen, the compound has a β

orientation at the C17 position.

15. The method according to claim 11, wherein said compound or pharmaceutically acceptable salt thereof is administered as part of a pharmaceutical composition, said composition further comprising at least one additional pharmaceutically active ingredient.

16. The method according to claim 15, wherein the at least one additional pharmaceutically active ingredient is selected from the group consisting of estrogenic compounds, androgenic compounds, progestin compounds, vasodilation agents, calcium salts, and vitamin D, and mixtures and combinations thereof.

17. The method according to claim 11, wherein the condition treatable by estrogen therapy is selected from the group consisting of vasomotor symptoms, atrophic vaginitis, osteoporosis, hypoestrogenism due to hypogonadism, hypoestrogenism due to castration, hypoestrogenism due to primary ovarian failure, breast cancer in selected persons with metastatic disease, advanced androgen-dependent carcinoma of the prostate, abnormal uterine bleeding, and kraurosis vulvae.