17,20(E)-dehydro vitamin D analogs and their uses

• US 7,741,313 B2
• Filed: 07/09/2007
• Issued: 06/22/2010
• 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: Plum, Lori A., DeLuca, Hector F., Clagett-Dame, Margaret, Tadi, Bulli Padmaja
• Primary Examiner(s): Qazi; Sabiha
• Application Number:
  US11/775,108
• Publication Number:
  US 20070249568A1
• Time in Patent Office: 1,079 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 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• 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 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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: Y02P 20/55 : Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

This invention discloses 17,20(E)-dehydro vitamin D analogs, and specifically 17(E)-1α,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin 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 and inflammatory diseases in humans as well as renal osteodystrophy and 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 17(20)-dehydro vitamin D compound having the formula:

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

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

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

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

g/date to about 1000 μ

g/day.

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

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

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

9. 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 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ having the formula;

10. The method of claim 9 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered orally.

11. The method of claim 9 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered parenterally.

12. The method of claim 9 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered transdermally.

13. The method of claim 9 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered in a dosage of from about 0.01 μ

g/day to about 1000 μ

g/day.

14. The method of claim 9 wherein the animal is a human.

15. The method of claim 9 wherein the animal is a domestic animal.

16. The method of claim 9 wherein the animal is an agricultural animal.

17. A method of treating acne comprising administering to a subject with acne an effective amount of a 17(20)-dehydro vitamin D compound having the formula:

18. The method of claim 17 wherein the vitamin D compound is administered orally.

19. The method of claim 17 wherein the vitamin D compound is administered parenterally.

20. The method of claim 17 wherein the vitamin D compound is administered rectally.

21. The method of claim 17 wherein the vitamin D compound is administered nasally.

22. The method of claim 17 wherein the vitamin D compound is administered orally.

23. The method of claim 17 wherein the vitamin D compound is administered sublingually.

24. The method of claim 17 wherein the vitamin D compound is administered transdermally.

25. The method of claim 17 wherein the vitamin D compound is administered in a dosage of from about 0.01 μ

g/day to about 1000 μ

g/day.

26. A method of treating acne comprising administering to a subject with acne an effective amount of 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ having the formula;

27. The method of claim 26 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered orally.

28. The method of claim 26 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered parenterally.

29. The method of claim 26 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered transdermally.

30. The method of claim 26 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered rectally.

31. The method of claim 26 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered nasally.

32. The method of claim 26 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered sublingually.

33. The method of claim 26 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered in a dosage of from about 0.01 μ

g/day to about 1000 μ

g/day.

34. A method of treating hypertension comprising administering to a subject with hypertension an effective amount of a 17(20)-dehydro vitamin D compound having the formula:

35. The method of claim 34 wherein the vitamin D compound is administered orally.

36. The method of claim 34 wherein the vitamin D compound is administered parenterally.

37. The method of claim 34 wherein the vitamin D compound is administered rectally.

38. The method of claim 34 wherein the vitamin D compound is administered nasally.

39. The method of claim 34 wherein the vitamin D compound is administered sublingually.

40. The method of claim 34 wherein the vitamin D compound is administered transdermally.

41. The method of claim 34 wherein the vitamin D compound is administered in a dosage of from about 0.01 μ

g/day to about 1000 μ

g/day.

42. A method of treating hypertension comprising administering to a subject with hypertension an effective amount of 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ having the formula;

43. The method of claim 42 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered orally.

44. The method of claim 42 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered parenterally.

45. The method of claim 42 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered transdermally.

46. The method of claim 42 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered rectally.

47. The method of claim 42 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered nasally.

48. The method of claim 42 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered sublingually.

49. The method of claim 42 wherein 17(E)-1α

,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D₃ is administered in a dosage of from about 0.01 μ

g/day to about 1000 μ

g/day.