2-methylene-19,26,27-trinor-(20S)-1α-hydroxyvitamin D3 and its uses

• US 7,713,952 B2
• Filed: 07/09/2007
• Issued: 05/11/2010
• Est. Priority Date: 11/22/2004
• Status: Expired due to Fees

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Grzywacz, Pawel K., Plum, Lori A., DeLuca, Hector F., Clagett-Dame, Margaret
• Primary Examiner(s): Qazi; Sabiha
• Application Number:
  US11/775,087
• Publication Number:
  US 20070249567A1
• Time in Patent Office: 1,037 Days
• Field of Search: 514/167, 552/653
• US Class Current: 514/167
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2602/24 the ring system containing nine carbon atoms, e.g. perhydroindane
• CPC Class Codes: C07C 401/00 Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

This invention discloses 2-methylene-19,26,27-trinor-(20S)-vitamin D analogs, and specifically 2-methylene-19,26,27-trinor-(20S)-1α-hydroxyvitamin D₃ and pharmaceutical uses therefor. This compound exhibits pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also has little, if any, calcemic activity and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as renal osteodystrophy. This compound may also be used for the treatment or prevention of obesity.

Claims

1. A method of treating obesity of an animal, inhibiting adipoctye differentiation, inhibiting SCD-1 gene transcription, and/or reducing body fat in an animal comprising administering to an animal in need thereof an effective amount of a compound having the formula:

2. The method of claim 1 wherein the compound is administered orally.

3. The method of claim 1 wherein the compound is administered parenterally.

4. The method of claim 1 wherein the compound is administered transdermally.

5. The method of claim 1 wherein the compound is administered rectally.

6. The method of claim 1 wherein the compound is administered nasally.

7. The method of claim 1 wherein the compound is administered sublingually.

8. The method of claim 1 wherein the compound is administered in a dosage of from about 0.01 μ

g/day to about 1000 μ

g/day.

9. The method of claim 1 wherein the compound is 2-methylene-19,26,27-trinor-(20S)-1α

-hydroxyvitamin D₃ having the formula;

10. The method of claim 1 wherein the animal is a human.

11. The method of claim 1 wherein the animal is a domestic animal.

12. The method of claim 1 wherein the animal is an agricultural animal.

13. A method of treating acne in an animal, the method comprising administering to an animal in need thereof an effective amount of a compound having the formula:

14. The method of claim 13 wherein the compound is administered orally.

15. The method of claim 13 wherein the compound is administered parenterally.

16. The method of claim 13 wherein the compound is administered transdermally.

17. The method of claim 13 wherein the compound is administered rectally.

18. The method of claim 13 wherein the compound is administered nasally.

19. The method of claim 13 wherein the compound is administered sublingually.

20. The method of claim 13 wherein the compound is administered in a dosage of from about 0.01 μ

g/day to about 1000 μ

g/day.

21. The method of claim 13 wherein the compound is 2-methylene-19,26,27-trinor-(20S)-1α

-hydroxyvitamin D₃ having the formula;

22. A method of treating hypertension in an animal, the method comprising administering to an animal in need thereof an effective amount of a compound having the formula:

23. The method of claim 22 wherein the compound is administered orally.

24. The method of claim 22 wherein the compound is administered parenterally.

25. The method of claim 22 wherein the compound is administered transdermally.

26. The method of claim 22 wherein the compound is administered rectally.

27. The method of claim 22 wherein the compound is administered nasally.

28. The method of claim 22 wherein the compound is administered sublingually.

29. The method of claim 22 wherein the compound is administered in a dosage of from about 0.01 μ

g/day to about 1000 μ

g/day.

30. The method of claim 22 wherein the compound is 2-methylene-19,26,27-trinor-(20S)-1α

-hydroxyvitamin D₃ having the formula;