Vitamin D analog—RAK, methods and uses thereof

• US 7,803,789 B2
• Filed: 01/30/2007
• Issued: 09/28/2010
• Est. Priority Date: 02/02/2006
• 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: Plum, Lori A., Clagett-Dame, Margaret, Grzywacz, Pawel, Deluca, Hector F., Chiellini, Grazia
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US11/669,053
• Publication Number:
  US 20070191317A1
• Time in Patent Office: 1,337 Days
• Field of Search: 514/167, 552/653
• US Class Current: 514/167
• CPC Class Codes: A61K 8/67 Vitamins
• 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 13/12 of the kidneys
• 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 17/16 Emollients or protectives, e.g. against radiation
• 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 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations
• 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

Compounds of formula IA or IB are provided where X₁, X₂ and X₃ are independently selected from H or hydroxy protecting groups and R₁ is selected from straight or branched chain alkyl groups having from 1 to 8 carbon atoms; straight or branched chain alkenyl groups having from 2 to 8 carbon atoms; straight or branched chain hydroxy-substituted alkyl groups having from 1 to 8 carbon atoms; straight and branched chain hydroxy-substituted alkenyl groups having from 2 to 8 carbon atoms. 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 IA or IB

2. The compound of claim 1, wherein X1, X2 and X3 are hydroxy protecting groups.

3. The compound of claim 2, wherein X1, X2 and X3 are t-butyldimethylsilyl groups.

4. The compound of claim 1, wherein X1, X2 and X3 are H and R1 is CH3 and the compound has the formula IIA or IIB

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 psoriasis;

leukemia;

colon cancer;

breast cancer;

prostate 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;

or osteoporosis;

Vitimin D resistant rickets;

or psoriatic arthritis.

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, 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 compound is administered orally, parenterally, transdermally or topically to the subject.

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

16. 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.

17. The compound having the formula IIA

18. A pharmaceutical composition, comprising an effective amount of the compound of claim 17 and a pharmaceutically acceptable carrier.

19. The compound having the formula IIB

20. A pharmaceutical compostion, comprising an effective amount of the compound of claim 19 and a pharmaceutically acceptble carrier.