Sidechain homo-vitamin D compounds with preferential anti-cancer activity

• US 4,717,721 A
• Filed: 05/30/1985
• Issued: 01/05/1988
• Est. Priority Date: 05/30/1985
• Status: Expired due to Fees

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Howard W. Bremer
• Inventors: Ostrem, Voula, DeLuca, Hector F., Schnoes, Heinrich K., Ikekawa, Nobuo
• Primary Examiner(s): Schenkman, Leonard
• Assistant Examiner(s): NOT, DEFINED
• Application Number:
  US06/739,332
• Time in Patent Office: 950 Days
• Field of Search: 514/167, 260/397.2
• US Class Current: 514/167
• 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 relates to a method for enhancing cell differentiation in malignant cells by exposing the cells to a 1α-hydroxylated vitamin D derivative characterized by a 17-side chain greater in length than the cholesterol or ergosterol side chains.

The method finds application in the treatment of neoplastic diseases including leukemoid diseases and, specifically, leukemia.

Claims

1. A method for inducing and enhancing cell differentiation in malignant cells which comprises exposing said cells to at least one 1 alpha-hydroxylated vitamin D derivative having the structure ##STR5## where R is a homo-steroid sidechain selected from the group consisting of ##STR6## in a molar concentration no greater than about 1×

10^-8 moles/liter but in an amount sufficient to induce and enhance cell differentiation.

2. The method of claim 1 where the 1α

-hydroxyvitamin D compound is 1α

,25-dihydroxyvitamin-24-homovitamin D₃.

3. The method of claim 1 where the 1α

-hydroxyvitamin D compound is 1α

,25-dihydroxy-22E-dehydro-24-homovitamin D₃.

4. The method of claim 1 where the 1α

-hydroxyvitamin D compound is 1α

,25-dihydroxy-26-homovitamin D₃.

5. The method of claim 1 where the 1α

-hydroxyvitamin D compound is 1α

,25-dihydroxy-22E-dehydro-26-homovitamin D₃.

6. A method for treating neoplastic diseases which comprises administering to a patient having a neoplastic disease a compound characterized by a high antineoplastic to calcemic activity ratio having the structure ##STR7## where R is a homo-steroid sidechain selected from the group consisting of ##STR8## in an amount that results in a blood serum concentration no greater that about 1×

10^-8 moles/liter but in an amount sufficient to induce the differentiation of malignant cells to macrophages.

7. A method according to claim 6 where the vitamin D derivative is 1α

,25-dihydroxy-24-homovitamin D₃.

8. A method according to claim 6 where the vitamin D derivative is 1α

,25-dihydroxy-22E-dehydro-24-homovitamin D₃.

9. A method according to claim 6 where the vitamin D derivative is 1α

,25-dihydroxy-26-homovitamin D₃.

10. A method according to claim 6 where the vitamin D derivative is 1α

,25-dihydroxy-22E-dehydro-26-homovitamin D₃.