2-ethyl and 2-ethylidene-19-nor-vitamin D compounds

• US 6,806,262 B2
• Filed: 05/31/2001
• Issued: 10/19/2004
• Est. Priority Date: 05/31/2000
• Status: Expired due to Term

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: DeLuca, Hector F., Sicinski, Rafal R.
• Primary Examiner(s): Badio, Barbara P.
• Application Number:
  US09/871,227
• Publication Number:
  US 20030013691A1
• Time in Patent Office: 1,237 Days
• Field of Search: 552/653, 514/167
• US Class Current: 514/167
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• 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 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• 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 19/10 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 3/10 for hyperglycaemia, e.g. antidiabetics
• 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 5/18 of the parathyroid hormones
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• 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

Biologically active 19-nor vitamin D analogs substituted at C-2 in the A-ring with an ethylidene or an ethyl group. These compounds have preferential activity on mobilizing calcium from bone and either high or normal intestinal calcium transport activity which allows their in vivo administration for the treatment of metabolic bone diseases where bone loss is a major concern. These compounds are also characterized by high cell differentiation activity.

Claims

1. 19-nor-2α

-ethyl-1α

,25-dihydroxyvitamin D₃.

2. 19-nor-2β

-ethyl-1α

,25-dihydroxyvitamin D₃.

3. 19-nor-20(S)-2α

-ethyl-1α

,25-dihydroxyvitamin D₃.

4. 19-nor-20(S)-2β

-ethyl-1α

,25-dihydroxyvitamin D₃.

5. 19-nor-2(E)-ethylidene-1α

,25-dihydroxyvitamin D₃.

6. 19-nor-2(Z)-ethylidene-1α

,25-dihydroxyvitamin D₃.

7. 19-nor-2(E)-ethylidene-20(S)-1α

,25-dihydroxyvitamin D₃.

8. 19-nor-2(Z)-ethylidene-20(S)-1α

,25-dihydroxyvitamin D₃.

9. A pharmaceutical composition containing 19-nor-2α

-ethyl-1α

,25-dihydroxyvitamin D₃ together with a pharmaceutically acceptable excipient.

10. The pharmaceutical composition of claim 9 containing 19-nor-2α

-ethyl-1α

,25-dihydroxyvitamin D₃ in an amount of from about 0.01 μ

g to about 100 μ

g per gram of the composition.

11. The pharmaceutical composition of claim 9 containing 19-nor-2α

-ethyl-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.1 μ

g to about 50 μ

g per gram of the composition.

12. The pharmaceutical composition of claim 9 suitable for oral administration.

13. The pharmaceutical composition of claim 9 suitable for topical administration.

14. The pharmaceutical composition of claim 9 suitable for parenteral administration.

15. A pharmaceutical composition containing 19-nor-2β

-ethyl-1α

,25-dihydroxyvitamin D₃ together with a pharmaceutically acceptable excipient.

16. The pharmaceutical composition of claim 15 containing 19-nor-2β

-ethyl-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.01 μ

g to about 100 μ

g per gram of the composition.

17. The pharmaceutical composition of claim 15 containing 19-nor-2β

-ethyl-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.1 μ

g to about 50 μ

g per gram of the composition.

18. The pharmaceutical composition of claim 15 suitable for oral administration.

19. The pharmaceutical composition of claim 15 suitable for topical administration.

20. The pharmaceutical composition of claim 15 suitable for parenteral administration.

21. A pharmaceutical composition containing 19-nor-20(S)-2α

-ethyl-1α

,25-dihydroxyvitamin D₃ together with a pharmaceutically acceptable excipient.

22. The pharmaceutical composition of claim 21 containing 19-nor-20(S)-2α

-ethyl-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.01 μ

g to about 100 μ

g per gram of the composition.

23. The pharmaceutical composition of claim 21 containing 19-nor-20(S)-2α

-ethyl-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.1 μ

g to about 50 μ

g per gram of the composition.

24. The pharmaceutical composition of claim 21 suitable for oral administration.

25. The pharmaceutical composition of claim 21 suitable for topical administration.

26. The pharmaceutical composition of claim 21 suitable for parenteral administration.

27. A pharmaceutical composition containing 19-nor-20(S)-2β

-ethyl-1α

,25-dihydroxyvitamin D₃ together with a pharmaceutically acceptable excipient.

28. The pharmaceutical composition of claim 27 containing 19-nor-20(S)-2β

-ethyl-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.01 μ

g to about 100 μ

g per gram of the composition.

29. The pharmaceutical composition of claim 27 containing 19-nor-20(S)-2β

-ethyl-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.01 μ

g to about 50 μ

g per gram of the composition.

30. The pharmaceutical composition of claim 27 suitable for oral administration.

31. The pharmaceutical composition of claim 27 suitable for topical administration.

32. The pharmaceutical composition of claim 27 suitable for parenteral administration.

33. A pharmaceutical composition containing 19-nor-2(E)-ethylidene-1α

,25-dihydroxyvitamin D₃ together with a pharmaceutically acceptable excipient.

34. The pharmaceutical composition of claim 33 containing 19-nor-2(E)-ethylidene-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.01 μ

g to about 100 μ

g per gram of the composition.

35. The pharmaceutical composition of claim 33 containing 19-nor-2(E)-ethylidene-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.1 μ

g to about 50 μ

g per gram of the composition.

36. The pharmaceutical composition of claim 33 suitable for oral administration.

37. The pharmaceutical composition of claim 33 suitable for topical administration.

38. The pharmaceutical composition of claim 33 suitable for parenteral administration.

39. A pharmaceutical composition containing 19-nor-2(Z) -ethylidene-1α

,25-dihydroxyvitamin D₃ together with a pharmaceutically acceptable excipient.

40. The pharmaceutical composition of claim 39 containing 19-nor-2(Z)-ethylidene-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.01 μ

g to about 100 μ

g per gram of the composition.

41. The pharmaceutical composition of claim 39 containing 19-nor-2(Z)-ethylidene-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.1 μ

g to about 50 μ

g per gram of the composition.

42. The pharmaceutical composition of claim 39 suitable for oral administration.

43. The pharmaceutical composition of claim 39 suitable for topical administration.

44. The pharmaceutical composition of claim 39 suitable for parenteral administration.

45. A pharmaceutical composition containing 19-nor-2(E) -ethylidene-20(S)-1α

,25-dihydroxyvitamin D₃ together with a pharmaceutically acceptable excipient.

46. The pharmaceutical composition of claim 45 containing 19-nor-2(E)-ethylidene-20(S)-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.01 μ

g to about 100 μ

g per gram of the composition.

47. The pharmaceutical composition of claim 45 containing 19-nor-2(E)-ethylidene-20(S)-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.1 μ

g to about 50 μ

g per gram of the composition.

48. The pharmaceutical composition of claim 45 suitable for oral administration.

49. The pharmaceutical composition of claim 45 suitable for topical administration.

50. The pharmaceutical composition of claim 45 suitable for parenteral administration.

51. A pharmaceutical composition containing 19-nor-2(Z) -ethylidene-20(S)-1α

,25-dihydroxyvitamin D₃ together with a pharmaceutically acceptable excipient.

52. The pharmaceutical composition of claim 51 containing 19-nor-2(Z)-ethylidene-20(S)-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.01 μ

g to about 100 μ

g per gram of the composition.

53. The pharmaceutical composition of claim 51 containing 19-nor-2(Z)-ethylidene-20(S)-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.1 μ

g to about 50 μ

g per gram of the composition.

54. The pharmaceutical composition of claim 51 suitable for oral administration.

55. The pharmaceutical composition of claim 51 suitable for topical administration.

56. The pharmaceutical composition of claim 51 suitable for parenteral administration.