Novel cyclopentano-vitamin D analogs

• US 4,851,401 A
• Filed: 07/14/1988
• Issued: 07/25/1989
• Est. Priority Date: 07/14/1988
• 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., Kutner, Andrzej, Schnoes, Heinrich K., Perlman, Kato L.
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): Lipovsky, Joseph A.
• Application Number:
  US07/219,101
• Time in Patent Office: 376 Days
• Field of Search: 260/397.2, 514/167
• US Class Current: 514/167
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• 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: 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

This invention provides novel 1α-hydroxyvitamin D compounds, methods for their preparation, and pharmaceutical compositions of these compounds. The new compounds, which are characterized structurally by having a cyclopentane ring as part of their side chains, exhibit highly pronounced biological activity, both in terms of their effect on calcium metabolism and their effect on differentiating malignant cells to normal cells. By virtue of their biological properties, the new vitamin D analogs are effective as calcium-regulating, or differentiation-inducing agents, and thus find application as therapeutic agents in the treatment or prophylaxis of bone-related as well as neoplastic diseases.

Claims

1. Compounds having the structure:

##STR6## wherein R¹, R², and R³, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, X is selected from the group consisting of hydrogen and phenylsulfonyl, Y is selected from the group consisting of hydrogen, hydroxy and protected hydroxy, and where X and Y, taken together, form a carbon-carbon bond.

2. The compounds as claimed in claim 1, where the hydroxy-protecting group is an acyl group, or an alkoxyalkyl group.

3. The compounds as claimed in claim 1, where the hydroxy-protecting group is an alkylsilyl group.

4. A pharmaceutical composition containing at least one of the compounds as claimed in claim 1 together with a pharmaceutically-acceptable excipient.

5. A pharmaceutical composition as claimed in claim 4, in which the compounds, alone or in combination, are present in an amount from about 0.1 to about 10 μ

g.

6. The compound having the structure:

##STR7##

7. A pharmaceutical composition containing the compound of claim 6 together with a pharmaceutically-acceptable excipient.

8. A pharmaceutical composition as claimed in claim 7, in which the compound is present in an amount from about 0.1 to about 10 μ

g.

9. The compound having the structure:

##STR8##

10. A pharmaceutical composition containing the compound of claim 9, together with a pharmaceutically-acceptable excipient.

11. A pharmaceutical composition as claimed in claim 10, in which the compound is present in an amount from about 0.1 to about 10 μ

g.