(22E)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin D3 analogs

Patent metadata

Field	Value
Publication number	US-9416102-B2
Application number	US-201314084281-A
Country	US
Kind code	B2
Filing date	Nov 19, 2013
Priority date	Jan 23, 2013
Publication date	Aug 16, 2016
Grant date	Aug 16, 2016

Abstract

Disclosed are (22E)-2-methylene-22-dehydro-1,24,25-trihydroxy-19-nor-vitamin D 3 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 D 3 and (22E)-(24S)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin D 3 , their biological activities, and various pharmaceutical uses for these compounds.

First claim

We claim:

1. A compound of the formula:

where X 1 , X 2 , X 3 , and X 4 , which are the same or different, are each selected from hydrogen or a hydroxy-protecting group.

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

3. The compound of claim 1 , wherein X 1 and X 2 are hydrogen.

4. The compound of claim 1 , wherein X 3 and X 4 are triethylsilyl.

5. The compound of claim 1 , wherein X 3 and X 4 are hydrogen.

6. The compound of claim 1 , wherein X 1 , X 2 , X 3 , and X 4 are hydrogen.

7. A compound of the formula:

and named (22E)-(24R)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin D 3 .

8. A compound of the formula:

and named (22E)-(24S)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin D 3 .

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

10. A pharmaceutical composition containing an effective amount of the compound of claim 8 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 .

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 .

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 .

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 .

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 .

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 .

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 .

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 .

Assignees

• Wisconsin Alumni Res Found

Inventors

• Deluca Hector F
• Plum Lori A
• Barycki Rafal
• Clagett-Dame Margaret

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P5/18

  of the parathyroid hormones · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61P3/02

  Nutrients, e.g. vitamins, minerals · CPC title

• C07C2601/14

  The ring being saturated · CPC title