2-methylene-1α-hydroxy-19,21-dinorvitamin D3 analogs and uses thereof

• US 7,648,972 B2
• Filed: 04/06/2007
• Issued: 01/19/2010
• Est. Priority Date: 04/06/2006
• Status: Expired due to Fees

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Barycki, Rafal, Plum, Lori A., DeLuca, Hector F., Clagett-Dame, Margaret
• Primary Examiner(s): Qazi; Sabiha
• Application Number:
  US11/697,418
• Publication Number:
  US 20070238702A1
• Time in Patent Office: 1,019 Days
• Field of Search: 552/653, 514/167
• US Class Current: 514/167
• 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 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• 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 3/04 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• 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

Compounds of formula I are provided where X₁ and X₂ are independently selected from H or hydroxy protecting groups. Such compounds are used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions.

Claims

1. A compound having the formula I

2. The compound of claim 1, wherein X₁ and X₂ are hydroxy protecting groups.

3. The compound of claim 2, wherein X₁ and X₂ are triethylsilyl or t-butyldimethylsilyl groups.

4. The compound of claim 1, wherein X₁ and X₂ is H and the compound has the formula II

5. A pharmaceutical composition, comprising an effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.

6. The pharmaceutical composition of claim 5 wherein the effective amount comprises from about 0.01 μ

g to about 1 mg of the compound per gram of the composition.

7. The pharmaceutical composition of claim 5 wherein the effective amount comprises from about 0.1 μ

g to about 500 μ

g of the compound per gram of the composition.

8. A method of treating a subject suffering from a biological condition, comprising administering an effective amount of the compound of claim 1 to the subject, wherein the biological condition is selected from a metabolic bone disease;

psoriasis;

leukemia;

colon cancer;

breast cancer;

prostate cancer;

skin cancer;

lung cancer;

multiple sclerosis;

lupus;

diabetes mellitus;

host versus graft reaction;

rejection of organ transplants;

an inflammatory disease selected from rheumatoid arthritis, asthma, or inflammatory bowel diseases;

a skin condition selected from wrinkles, lack of adequate skin firmness, lack of adequate dermal hydration, or insufficient sebum secretion;

renal osteodystrophy;

osteopenia;

or osteoporosis.

9. The method of claim 8, wherein the biological condition is renal osteodystrophy, vitamin D-resistant rickets, osteoporosis or psoriatic arthritis.

10. The method of claim 8, wherein the biological condition is selected from leukemia, colon cancer, breast cancer, skin cancer, lung cancer or prostate cancer.

11. The method of claim 8, wherein the biological condition is selected from multiple sclerosis, lupus, diabetes mellitus, host versus graft reaction, or rejection of organ transplants.

12. The method of claim 8, wherein the biological condition is selected from rheumatoid arthritis, asthma, or inflammatory bowel diseases selected from celiac disease, ulcerative colitis and Crohn'"'"'s disease.

13. The method of claim 8, wherein the biological condition is selected from wrinkles, lack of adequate skin firmness, lack of adequate dermal hydration, or insufficient sebum secretion.

14. The method of claim 8 wherein the biological condition is metabolic bone disease.

15. The method of claim 8, wherein the compound is administered orally, parenterally, nasally, rectally, sublingually, transdermally or topically to the subject.

16. The method of claim 8, wherein the compound is administered intraperitoneally.

17. The method of claim 8, wherein the compound is administered in a dosage of from 0.01 μ

g per day to 1 mg per day.

18. A compound having the formula II

19. A pharmaceutical composition, comprising an effective amount of the compound of claim 18 and a pharmaceutically acceptable carrier.

20. The pharmaceutical composition of claim 19 wherein the effective amount comprises from about 0.01 μ

g to about 1 mg of the compound per gram of the composition.

21. The pharmaceutical composition of claim 19 wherein the effective amount comprises from about 0.1 μ

g to about 500 μ

g of the compound per gram of the composition.

22. 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 a compound having the formula:

23. The method of claim 22, wherein the compound is administered orally, parenterally, nasally, rectally, sublingually, transdermally or topically to the animal.

24. The method of claim 22, wherein the compound is administered in a dosage of from 0.01 μ

g per day to 1 mg per day.

25. The method of claim 22, wherein the compound is 2-methylene-1α

-hydroxy-19,21-dinorvitamin D₃ having the formula;

26. The method of claim 22, wherein the animal is a human.

27. The method of claim 22, wherein the animal is a domestic animal.

28. The method of claim 22, wherein the animal is an agricultural animal.