19,26,27-trinor-1alpha,25-dihydroxyvitamin D3 compounds

• US 20060264410A1
• Filed: 05/02/2006
• Published: 11/23/2006
• Est. Priority Date: 05/03/2005
• Status: Active Grant

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Plum, Lori A., DeLuca, Hector F., Clagett-Dame, Margaret, Grzywacz, Pawel
• Granted Patent: US 7,241,909 B2
• Time in Patent Office: Days
• US Class Current: 514/167
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• 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 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 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• 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 1 are provided where X¹, X², and X³ are independently selected from H or hydroxy protecting groups, and R¹ and R² have the definitions provided herein. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions.

Claims

1. A compound having the formula 1,

2. The compound of claim 1, wherein X³ is H, and the compound of formula 1 has the formula 1A

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

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

5. The compound of claim 2, wherein X¹ and X² are both H and the compound has the formula 3A

6. The compound of claim 2, wherein X¹ and X² are both H and the compound has the formula 3B

7. The compound of claim 2, wherein X¹ and X² are both H and the compound has the formula 3C

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

9. The pharmaceutical composition of claim 8, wherein the effective amount comprises from about 0.01 μ

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

10. The pharmaceutical composition of claim 9, wherein the effective amount comprises from about 0.1 μ

g to about 500 μ

g of the compound per gram of the composition.

11. The pharmaceutical composition of claim 8, wherein X³ is H.

12. The pharmaceutical composition of claim 11, wherein X¹ and X² are both H.

13. A method of treating a subject suffering from a biological disorder, comprising administering an effective amount of the compound of claim 1 to the subject.

14. The method of claim 13, wherein the biological disorder is a condition where a rise in serum calcium is undesirable, and the disorder is selected from renal osteodystrophy, secondary hyperparathyroidism, psoriasis, type I diabetes, lupus, rheumatoid arthritis, or a cancer selected from leukemia, colon cancer, breast cancer, or prostate cancer.

15. The method of claim 13, wherein the biological disorder is hypercalcemia, asthma, or eczema.

16. The method of claim 13, wherein the compound or composition is administered orally, parenterally, rectally, transdermally, or topically to the subject.

17. The method of claim 13, wherein the compound or composition is administered by delivering the compound, mixture of compounds or pharmaceutical formulation in an aerosol.

18. The method of claim 13, wherein the compound, or the mixture of compounds is administered in a dosage of from 0.01 μ

g per day to 1 mg per day.

19. The method of claim 13, wherein X¹, X², and X³ are all H.

20. The method of claim 19, wherein the compound has the formula