Estrogenic compounds, pharmaceutical compositions thereof, and methods of using same

• US 6,660,726 B2
• Filed: 03/08/2001
• Issued: 12/09/2003
• Est. Priority Date: 03/10/2000
• Status: Expired due to Term

• Current Assignee: Duramed Pharmaceuticals Incorporated (Teva Pharmaceutical Industries Limited)
• Original Assignee: Endeavor Pharmaceuticals, Inc. (Teva Pharmaceutical Industries Limited)
• Inventors: Hill, Edward N., Whittle, Robert R., Sancilio, Frederick D.
• Primary Examiner(s): Badio, Barbara P.
• Application Number:
  US09/800,614
• Publication Number:
  US 20020016316A1
• Time in Patent Office: 1,006 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 alkyl, 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 the following Formula:

or a pharmaceutically acceptable salt thereof;

said compound being present in chemically pure form; and

said compound has the following physicochemical properties;

having a peak located at about 1.2 ppm on a ¹H-NMR; and

having a peak located at about 45 ppm on a ¹³C-NMR.

2. The compound according to claim 1, wherein the compound is a sodium salt of a sulfate thereof.

3. A compound represented by the following Formula:

or a pharmaceutically acceptable salt thereof;

said compound being present in chemically pure form; and

said compound has the following physicochemical properties;

having a peak located at about 1.2 ppm on a ¹H-NMR; and

having a peak located at about 45 ppm on a ¹³C-NMR.

4. The compound according to claim 3, wherein the compound is a sodium salt of a sulfate thereof.

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

or a pharmaceutically acceptable salt thereof;

said compound being present in chemically pure form and said compound has the following physicochemical properties;

having a peak located at about 1.2 ppm on a ¹H-NMR; and

having a peak located at about 45 ppm on a ¹³C-NMR.

6. A pharmaceutical composition incorporating a compound represented by the following Formula:

or a pharmaceutically acceptable salt thereof;

said compound being present in chemically pure form and said compound has the following physicochemical properties;

having a peak located at about 1.2 ppm on a ¹H-NMR; and

having a peak located at about 45 ppm on a ¹³C-NMR.

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

or a pharmaceutically acceptable salt thereof;

said compound being present in chemically pure form and wherein said compound has the following physicochemical properties;

having a peak located at about 1.2 ppm on a ¹H-NMR; and

having a peak located at about 45 ppm on a ¹³C-NMR.

8. The method according to claim 7, wherein the compound is a sodium salt of a sulfate thereof.

9. The method according to claim 7, 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 vulvac.

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

or a pharmaceutically acceptable salt thereof;

said compound being present in chemically pure form and wherein said compound has the following physicochemical properties;

having a peak located at about 1.2 ppm on a ¹H-NMR; and

having a peak located at about 45 ppm on a ¹³C-NMR.

11. The method according to claim 10, wherein the compound is a sodium salt of a sulfate thereof.

12. The method according to claim 10, 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.