Hydroxylated 26-homo vitamin D derivatives and methods for preparing same

• US 4,851,400 A
• Filed: 03/03/1986
• Issued: 07/25/1989
• Est. Priority Date: 01/17/1985
• Status: Expired due to Fees

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: DeLuca, Hector F., Tanaka, Yoko, Ikekawa, Nobuo
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): Lipovsky, Joseph A.
• Application Number:
  US06/835,711
• Time in Patent Office: 1,240 Days
• Field of Search: 260/397.2, 514/167
• US Class Current: 514/167
• 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: A61P 35/00 Antineoplastic agents
• 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

Abstract

This invention is directed to new 26-homo-vitamin D compounds, to methods for preparing the same and novel intermediate compounds.

The compounds are characterized by vitamin D-like activity of the order of 1α,25-dihydroxyvitamin D₃, the recognized circulating hormonal form of vitamin D, or various of its derivatives and by greater antineoplastic activity than such compounds but without their attendant calcemic activity. The compounds are useful in the treatment of disease states characterized by calcium-phosphorous imbalances and where antineoplastic activity is indicated.

Claims

1. Compounds having the formula ##STR2## where R₁, R₂ and R₃ are selected from the group consisting of hydrogen, an acyl group having from 1 to about 4 carbon atoms and benzoyl, and R₄ and R₅ each represent hydrogen atoms or taken together form a carbon to carbon double bond.

2. A compound according to claim 1 wherein R₁, R₂ and R₃ are hydrogen and R₄ and R₅ are hydrogen atoms.

3. The compounds of claim 2 in crystalline form.

4. A composition comprising the compound of claim 2 and a pharmaceutically acceptable excipient.

5. A compound according to claim 2 wherein the Δ

²² bond is in the E configuration.

6. A compound according to claim 1 wherein R₁, R₂ and R₃ are hydrogen and R₄ and R₅ together represent a carbon to carbon double bond.

7. The compound of claim 6 in crystalline form.

8. Compounds having the formula ##STR3## wherein R₁, R₂ and R₃ are selected from the group consisting of hydrogen, an acyl group having from 1 to about 4 carbon atoms and benzoyl and R₄ and R₅ represent hydrogen atoms or taken together form a carbon to carbon double bond, with the proviso that when R₄ and R₅ represent a carbon to carbon double bond and R₃ is hydrogen, R₁ and R₂ may also be methoxymethyl.

9. Compounds having the formula ##STR4## wherein R₁, R₂ and R₃ are selected from the group consisting of hydrogen, an acyl group having from 1 to about 4 carbon atoms and benzoyl and R₄ and R₅ represent hydrogen atoms or taken together form a carbon to carbon double bond.