2-Methylene-19-nor-20(S)-25-methyl-1alpha-hydroxycalciferol and its uses

• US 20050004085A1
• Filed: 09/08/2003
• Published: 01/06/2005
• Est. Priority Date: 07/03/2003
• 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., Grzywacz, Pawel K.
• Granted Patent: US 6,894,037 B2
• Time in Patent Office: Days
• US Class Current: 514/167
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/10 for osteoporosis
• 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 35/02 specific for leukemia
• 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 provides a novel vitamin D analog, namely, 2-methylene-19-nor-20(S)-25-methyl-1α-hydroxycalciferol. The compound has the formula: This 2-substituted compound is characterized by relatively high intestinal calcium transport activity and relatively low bone calcium mobilization activity resulting in novel therapeutic agents for the treatment of diseases where bone formation is desired, particularly osteoporosis. These compounds also exhibit pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as anti-cancer agents and for the treatment of diseases such as psoriasis.

Claims

1. A compound having the formula:

3. A pharmaceutical composition containing at least one compound as claimed in claim 1 together with a pharmaceutically acceptable excipient.

4. The pharmaceutical composition of claim 3 containing 2-methylene-19-nor-20(S)-25-methyl-1 α

-hydroxycalciferol in an amount from about 0.01 μ

g to about 100 μ

g.

5. The pharmaceutical composition of claim 3 containing 2-methylene-19-nor-20(S)-25-methyl-1α

-hydroxycalciferol in an amount from about 0.1 μ

g to about 50 μ

g.

2. 2-methylene-19-nor-20(S)-25-methyl-1α

-hydroxycalciferol.

6. A method of treating metabolic bone disease where it is desired to maintain or increase bone mass comprising administering to a patient with said disease an effective amount of a compound having the formula:

7. The method of claim 6 where the disease is senile osteoporosis.

8. The method of claim 6 where the disease is postmenopausal osteoporosis.

9. The method of claim 6 where the disease is steroid-induced osteoporosis.

10. The method of claim 6 where the disease is low bone turnover osteoporosis.

11. The method of claim 6 where the disease is osteomalacia.

12. The method of claim 6 where the disease is renal osteodystrophy.

13. The method of claim 6 wherein the compound is administered orally.

14. The method of claim 6 wherein the compound is administered parenterally.

15. The method of claim 6 wherein the compound is administered transdermally.

16. The method of claim 6 wherein the compound is administered in a dosage of from 0.01 g to 100 μ

g per day.

17. The method of claim 6 wherein the compound is 2-methylene-19-nor-20(S)-25-methyl-1α

-hydroxycalciferol.

18. A method of treating psoriasis comprising administering to a patient with said disease an effective amount of a compound having the formula:

19. The method of claim 18 wherein the compound is 2-methylene-19-nor-20(S)-25-methyl-1α

-hydroxycalciferol.

20. The method of claim 18 wherein said effective amount comprises about 0.01 μ

g/day to about 100 μ

g/day of said compound.

21. A method of treating a cancerous disease comprising administering to a patient with said disease an effective amount of a compound having the formula:

22. The method of claim 21 where the disease is leukemia.

23. The method of claim 21 where the disease is colon cancer.

24. The method of claim 21 where the disease is breast cancer.

25. The method of claim 21 where the disease is prostate cancer.

26. The method of claim 21 wherein the compound is administered orally.

27. The method of claim 21 wherein the compound is administered parenterally.

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

29. The method of claim 21 wherein the compound is 2-methylene-19-nor-20(S)-25-methyl-1α

-hydroxycalciferol.

30. The method of claim 21 wherein the compound is administered in a dosage of from 0.01 μ

g to 100 μ

g per day.

31. (Original) (20S)-de-A,B-25-methylcholestan-8-one having the formula: