24-cyclopropane vitamin D derivatives

• US 5,194,431 A
• Filed: 07/08/1992
• Issued: 03/16/1993
• Est. Priority Date: 07/08/1992
• Status: Expired due to Term

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: DeLuca, Hector F., Nakagawa, Naoshi
• Primary Examiner(s): Cintins, Marianne M.
• Assistant Examiner(s): PRIOR, KIMBERLY
• Application Number:
  US07/910,423
• Time in Patent Office: 251 Days
• Field of Search: 552/653, 552/508, 552/541, 514/167
• US Class Current: 514/167
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• 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: 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: C07J 9/00 Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane

Abstract

Vitamin D₂ analogs in which a cyclopropane ring is introduced onto the 24-carbon of the side chain of 1α,25-dihydroxyvitamin D₂ and 1α-hydroxyvitamin D₂. The compounds are characterized by a marked intestinal calcium transport activity while exhibiting much lower activity than 1α,25-dihydroxy-vitamin D₃ in their ability to mobilize calcium from bone. Because of their preferential calcemic activity, these compounds would be useful for the treatment of diseases where bone formation is desirbed, such as osteoporosis.

Claims

1. A compound having the formula

where R¹ is hydrogen or hydroxy.

14. A pharmaceutical composition containing at least one compound as claimed in claim 1 together with a pharmaceutically acceptable excipient.

15. The pharmaceutical composition of claim 14 containing 24,28-methylene-1α

,25-dihydroxyvitamin D₂ in an amount from about 0.5 μ

g to about 50 μ

g.

16. The pharmaceutical composition of claim 14 containing 24,28-dimethylene-1α

-dihydroxy-vitamin D₂ in amount from about 0.5 μ

g to about 50 μ

g.

2. 24,28-methylene-1α

,25-dihydroxyvitamin D₂.

3. 24,28-methylene-1α

-hydroxyvitamin D₂.

4. A method of treating metabolic bone disease where it is desired to maintain or increase bone mass comprising administering to a patient with said disease a compound having the formula ##STR4## where R¹ is hydrogen or hydroxy.

5. The method of claim 4 where the disease is osteoporosis.

6. The method of claim 4 where the disease is osteomalacia.

7. The method of claim 4 where the disease is renal osteodystrophy.

8. The method of claim 4 wherein the compound is administered orally.

9. The method of claim 4 wherein the compound is administered parenterally.

10. The method of claim 4 wherein the compound is administered transdermally.

11. The method of claim 4 wherein the compound is administered in a dosage of from 0.5 μ

g to 50 μ

g per day.

12. A compound having the formula ##STR5## where R² is hydrogen or hydroxy, R³ is a hydroxy-protecting group and R⁴ is hydrogen or a hydroxy-protecting group.

13. The compound of claim 12 where R² and R⁴ are both hydrogen and R³ is a hydroxy-protecting group.