2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-vitamin D analogs

• US 10,479,764 B2
• Filed: 06/26/2012
• Issued: 11/19/2019
• Est. Priority Date: 06/28/2011
• Status: Active Grant

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: DeLuca, Hector F., Clagett-Dame, Margaret, Plum, Lori A., Barycki, Rafal
• Primary Examiner(s): Badio, Barbara P
• Application Number:
  US13/533,018
• Publication Number:
  US 20130005686A1
• Time in Patent Office: 2,702 Days
• Field of Search: 552653
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• 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 19/04 for non-specific disorders of the connective tissue
• 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 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 5/20 for decreasing, blocking or antagonising the activity of PTH
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• 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

Abstract

This invention discloses 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-vitamin D analogs, and specifically 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-1α-hydroxyvitamin D₃, and pharmaceutical uses therefor. This compound exhibits relatively high transcription activity as well as 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 shows low activity in vivo on bone calcium mobilization, 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 psoriasis comprising administering to a subject with psoriasis an effective amount of 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-1α

-hydroxyvitamin D₃.

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 topically.

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

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

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

9. 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.

10. A method of treating a disease selected from the group consisting of leukemia, colon cancer, breast cancer, skin cancer or prostate cancer comprising administering to a subject with said disease an effective amount of 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-1α

-hydroxyvitamin D₃.

11. The method of claim 10 wherein the compound is administered orally.

12. The method of claim 10 wherein the compound is administered parenterally.

13. The method of claim 10 wherein the compound is administered transdermally.

14. The method of claim 10 wherein the compound is administered rectally.

15. The method of claim 10 wherein the compound is administered nasally.

16. The method of claim 10 wherein the compound is administered sublingually.

17. The method of claim 10 wherein the compound is administered in a dosage of from about 0.01 μ

g/day to about 1000 μ

g/day.

18. A method of treating an autoimmune disease selected from the group consisting of multiple sclerosis, lupus, diabetes mellitus, host versus graft rejection, and rejection of organ transplants, comprising administering to a subject with said disease an effective amount of 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-1α

-hydroxyvitamin D₃.

19. The method of claim 18 wherein the compound is administered orally.

20. The method of claim 18 wherein the compound is administered parenterally.

21. The method of claim 18 wherein the compound is administered transdermally.

22. The method of claim 18 wherein the compound is administered rectally.

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

24. The method of claim 18 wherein the compound is administered sublingually.

25. The method of claim 18 wherein the 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 a skin condition selected from the group consisting of wrinkles, lack of adequate skin firmness, lack of adequate dermal hydration and insufficient sebum secretion which comprises administering to a subject with said skin condition an effective amount of a 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-1α

-hydroxyvitamin D₃.

27. The method of claim 26 wherein the compound is administered orally.

28. The method of claim 26 wherein the compound is administered parenterally.

29. The method of claim 26 wherein the compound is administered transdermally.

30. The method of claim 26 wherein the compound is administered topically.

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

32. The method of claim 26 wherein the compound is administered nasally.

33. The method of claim 26 wherein the compound is administered sublingually.

34. The method of claim 26 wherein the compound is administered in a dosage of from about 0.01 μ

g/day to about 1000 μ

g/day.

35. A method of treating renal osteodystrophy comprising administering to a subject with renal osteodystrophy an effective amount of 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-1α

-hydroxyvitamin D₃.

36. The method of claim 35 wherein the compound is administered orally.

37. The method of claim 35 wherein the compound is administered parenterally.

38. The method of claim 35 wherein the compound is administered transdermally.

39. The method of claim 35 wherein the compound is administered rectally.

40. The method of claim 35 wherein the compound is administered nasally.

41. The method of claim 35 wherein the compound is administered sublingually.

42. The method of claim 35 wherein the compound is administered in a dosage of from about 0.01 μ

g/day to about 1000 μ

g/day.

43. A method of treating obesity of an animal, inhibiting adipocyte 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 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-1α

-hydroxyvitamin D₃.

44. The method of claim 43 wherein the compound is administered orally.

45. The method of claim 43 wherein the compound is administered parenterally.

46. The method of claim 43 wherein the compound is administered transdermally.

47. The method of claim 43 wherein the compound is administered rectally.

48. The method of claim 43 wherein the compound is administered nasally.

49. The method of claim 43 wherein the compound is administered sublingually.

50. The method of claim 43 wherein the compound is administered in a dosage of from about 0.01 μ

g/day to about 1000 μ

g/day.

51. The method of claim 43 wherein the animal is a human.

52. The method of claim 43 wherein the animal is a domestic animal.

53. The method of claim 43 wherein the animal is an agricultural animal.