24-hydroxyvitamin D, analogs and uses thereof

• US 7,122,530 B2
• Filed: 01/03/2001
• Issued: 10/17/2006
• Est. Priority Date: 05/29/1998
• Status: Expired due to Fees

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Bishop, Charles W., Knutson, Joyce C., Strugnell, Stephen
• Primary Examiner(s): Wang, Shengjun
• Assistant Examiner(s): CHONG, YONG SOO
• Application Number:
  US09/753,697
• Publication Number:
  US 20010002397A1
• Time in Patent Office: 2,113 Days
• Field of Search: 514/167
• US Class Current: 514/168
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/592 9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
• CPC Class Codes: A61P 13/08 of the prostate
• 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 19/10 for osteoporosis
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: A61P 5/20 for decreasing, blocking or antagonising the activity of PTH
• 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

The invention provides 24-hydroxyvitamin D compounds and methods for their use in the treatment and prophylaxis of hyperparathyroidism and hyperproliferative diseases, and in the modulation of the immune and inflammatory responses as well as the treatment of bone depletive disorders.

Claims

1. A method of achieving an effect in a patient in need thereof comprising administering an effective amount of a vitamin D compound which is a 24-hydroxyvitamin D compound wherein the effect is treating hyperparathyroidism, and wherein said 24-hydroxyvitamin D is a compound of formula (I):

6. The method of claim 1, wherein said 24-hydroxyvitamin D compound is administered in a dosage of about 3.5 μ

g to about 1000 μ

g/week.

11. The method of claim 1, wherein the effect is treating hyperparathyroidism.

12. The method of claim 1, wherein the vitamin D compound is 24-hydroxy-19-nor-vitamin D.

13. The method of claim 1, wherein the vitamin D compound is 24-hydroxyvitamin D₂.

2. A method of achieving an effect in a patient in need thereof comprising administering an effective amount of a vitamin D compound which is a 24-hydroxyprevitamin D, wherein the effect is treating hyperparathyroidism, wherein said 24-hydroxyprevitamin D is a compound of formula (III):

7. The method of claim 2 wherein Z is a side chain of formula (IIB).

8. The method of claim 7, wherein said 24-hydroxyprevitamin D is 24-hydroxyprevitamin D₂;

24(S)-hydroxyprevitamin D₂;

24-hydroxyprevitamin D₄;

or 24(R)-hydroxyprevitamin D₄.

9. The method of claim 2 wherein Z is a side chain of formula (IID).

10. The method of claim 9 wherein said 24-hydroxyprevitamin D compound is 24-OH-25-ene-preD₂.

14. The method of claim 2, wherein the effect is treating hyperparathyroidism.

15. The method of claim 2, wherein the vitamin D compound is 24-hydroxyprevitamin D₂.

3. A method of achieving an effect in a patient in need thereof comprising administering an effective amount of a vitamin D compound which is a 24-hydroxyvitamin D, wherein the effect is lowering or maintaining lowered parathyroid hormone levels, and wherein the 24-hydroxyvitamin D is a compound of formula (I):

16. The method of claim 3, wherein the effect is lowering or maintaining lowered parathyroid hormone level.

17. The method of claim 3, wherein the vitamin D compound is 24-hydroxy-19-nor-vitamin D.

18. The method of claim 3, wherein the vitamin D compound is 24-hydroxyvitamin D₂.

4. A method of achieving an effect in a patient in need thereof comprising administering an effective amount of a vitamin D compound which is a 24-hydroxyprevitamin D wherein the effect is lowering or maintaining lowered parathyroid hormone levels, wherein said 24-hydroxyprevitamin D is a compound of formula (III):

19. The method of claim 4 wherein the effect is lowering or maintaining lowered parathyroid hormone level.

20. The method of claim 4, wherein the vitamin D compound is 24-hydroxyprevitamin D₂.

5. A method of treating a human in need thereof to alleviate the pathological effects of hyperparathyroidism, wherein the method comprises administering to the human in need thereof a vitamin D compound which is a 24-hydroxyvitamin D of formula (I), wherein said compound is administered to the human in need thereof in an amount sufficient to lower or maintain lowered parathyroid hormone level in the human in need thereof;

wherein formula (I) is;

21. The method of claim 5 wherein the method of treatment alleviates the pathological effects of hyperparathyroidism.

22. The method of claim 5 wherein the vitamin D compound is administered to the human in an amount sufficient to lower or maintain lowered parathyroid hormone level.

23. The method of claim 5, wherein the vitamin D compound is 24-hydroxy-19-nor-vitamin D.

24. The method of claim 5, wherein the vitamin D compound is 24-hydroxyvitamin D₂.

25. The method of claim 5 wherein the Z side chain is formula IIB.

26. The method of claim 25, wherein said 24-hydroxyvitamin D is 24-hydroxyvitamin D₂;

24(S)-hydroxyvitamin D₂;

24-hydroxyvitamin D₄;

24(R)-hydroxyvitamin D₄.

27. The method of claim 5 wherein the Z side chain is formula IID.

28. The method of claim 5 wherein the Z side chain is formula IIF.

29. A method of treating a human in need thereof to alleviate the pathological effects of hyperparathyroidism, wherein the method comprises administering to the human in need thereof a vitamin D compound which is a 24-hydroxyprevitamin D of formula (III), wherein said compound is administered to the human in need thereof in an amount sufficient to lower elevated or maintain lowered parathyroid hormone level in the human in need thereof;

wherein formula (III) is;

30. The method of claim 29 wherein the method of treatment alleviates the pathological effects of hyperparathyroidism.

31. The method of claim 29 wherein the Z side chain is formula IIB.

32. The method of claim 29, wherein said 24-hydroxyprevitamin D is 24-hydroxyprevitamin D₂;

24(S)-hydroxyprevitamin D₂;

24-hydroxyprevitamin D₄;

24(R)-hydroxyprevitamin D₄.

33. The method of claim 32, wherein the vitamin D compound is 24-hydroxyprevitamin D₂.

34. The method of claim 29 wherein the Z side chain is formula IID.

35. The method of claim 29 wherein the Z side chain is formula IIF.