2-Propylidene-19-nor-vitamin d compounds

• US 20060293291A1
• Filed: 04/09/2004
• Published: 12/28/2006
• Est. Priority Date: 04/10/2003
• Status: Abandoned Application

• Current Assignee: Agnieszka Glebocka, Hector F. Deluca, Lori A. Plum, Rafal R. Sicinski
• Original Assignee: Agnieszka Glebocka, Hector F. Deluca, Lori A. Plum, Rafal R. Sicinski
• Inventors: DeLuca, Hector F, Plum, Lori A., Sicinski, Rafal R., Glebocka, Agnieszka
• Application Number:
  US10/544,163
• Publication Number:
  US 20060293291A1
• Time in Patent Office: Days
• 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 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• 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 19/08 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 3/10 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 37/06 Immunosuppressants, e.g. drugs for graft rejection
• 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
• CPC Class Codes: C07F 7/1804 : Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: Y02P 20/55 : Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

2-propylidene-19-nor-vitamin D compounds are disclosed as well as pharmaceutical uses for these compounds and methods of synthesizing these compounds. These compounds are characterized by high bone calcium mobilization activity and high intestinal calcium transport activity. This results in novel therapeutic agents for the treatment and prophylaxis of diseases where bone formation is desired, particularly osteoporosis, as well as autoimmune diseases such as multiple sclerosis, diabetes mellitus and lupus. These compounds also exhibit 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. These compounds also increase both breaking strength and crushing strength of bones evidencing use in conjunction with bone replacement surgery such as hip and knee replacements.

Claims

1. A compound having the formula:

2. The compound of claim 1 where R is a side chain of the formula

3. The compound of claim 1 where R is a side chain of the formula

4. The compound of claim 1 where R is a side chain of the formula

5. The compound of claim 1 where R is a side chain of the formula

6. The compound of claim 1 where R is a side chain of the formula

7. The compound of claim 1 where R is a side chain of the formula

8. The compound of claim 1 where R is a side chain of the formula

9. The compound of claim 1 where R is a side chain of the formula

10. The compound of claim 1 where R is a side chain of the formula

11. The compound of claim 1 where R is a side chain of the formula

17. A pharmaceutical composition containing an effective amount of at least one compound as claimed in claim 1 together with a pharmaceutically acceptable excipient.

18. The pharmaceutical composition of claim 17 wherein said effective amount comprises from about 0.01 μ

g to about 100 μ

g per gram of composition.

20. The pharmaceutical composition of claim 17 containing 2-[(3′

-methoxymethoxy)propylidene]-19-nor-1α

,25-(OH)₂,D₃ in an amount from about 0.01 μ

g to about 100 μ

g.

22. The pharmaceutical composition of claim 17 containing 2-(3′

-hydroxypropylidene)-19-nor-1α

,25-(OH)₂D₃ (E-isomer) in an amount from about 0.01 μ

g to about 100 μ

g.

24. The pharmaceutical composition of claim 17 containing 2-(3′

-hydroxypropylidene)-19-nor-1α

,25-(OH)₂D₃ (Z-isomer) in an amount from about 0.01 μ

g to about 100 μ

g.

26. The pharmaceutical composition of claim 17 containing 2-(3′

-hydroxypropylidene)-19-nor-(20S)-1α

,25-(OH)₂D₃ (E-isomer) in an amount from about 0.01 μ

g to about 100 μ

g.

28. The pharmaceutical composition of claim 17 containing 2-(3′

-hydroxypropylidene)-19-nor-(20S)-1α

,25-(OH)₂D₃ (Z-isomer) in an amount from about 0.01 μ

g to about 100 μ

g.

12-16. -16. (canceled)

19. (canceled)

21. (canceled)

23. (canceled)

25. (canceled)

27. (canceled)

29-109. -109. (canceled)