(22E)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin D;analogs

• US 9,416,102 B2
• Filed: 11/19/2013
• Issued: 08/16/2016
• Est. Priority Date: 01/23/2013
• 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., Plum, Lori A., Barycki, Rafal, Clagett-Dame, Margaret
• Primary Examiner(s): Badio, Barbara P
• Application Number:
  US14/084,281
• Publication Number:
  US 20140206655A1
• Time in Patent Office: 1,001 Days
• Field of Search: 552/653, 514/167
• US Class Current: 1/1
• CPC Class Codes: A61K 31/592 9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2602/24 the ring system containing nine carbon atoms, e.g. perhydroindane
• 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

Disclosed are (22E)-2-methylene-22-dehydro-1,24,25-trihydroxy-19-nor-vitamin D₃ compounds, their biological activities, and various pharmaceutical uses for these compounds. Particularly disclosed are (22E)-(24R)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin D₃ and (22E)-(24S)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin D₃, their biological activities, and various pharmaceutical uses for these compounds.

Claims

1. A compound of the formula:

2. The compound of claim 1, wherein X₁ and X₂ are t-butyldimethylsilyl.

3. The compound of claim 1, wherein X₁ and X₂ are hydrogen.

4. The compound of claim 1, wherein X₃ and X₄ are triethylsilyl.

5. The compound of claim 1, wherein X₃ and X₄ are hydrogen.

6. The compound of claim 1, wherein X₁, X₂, X₃, and X₄ are hydrogen.

7. A compound of the formula:

9. A pharmaceutical composition containing an effective amount of the compound of claim 7 and a pharmaceutically acceptable excipient.

11. A method of treating osteoporosis in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound of claim 7.

13. A method for increasing bone strength in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound of claim 7.

15. A method of treating leukemia in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound of claim 7.

17. A method of treating secondary hyperparathyroidism of renal osteodystrophy in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound of claim 7.

8. A compound of the formula:

10. A pharmaceutical composition containing an effective amount of the compound of claim 8 and a pharmaceutically acceptable excipient.

12. A method of treating osteoporosis in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound of claim 8.

14. A method for increasing bone strength in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound of claim 8.

16. A method of treating leukemia in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound of claim 8.

18. A method of treating secondary hyperparathyroidism of renal osteodystrophy in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound of claim 8.