Rhenium complexes

• US 5,496,533 A
• Filed: 07/26/1993
• Issued: 03/05/1996
• Est. Priority Date: 07/31/1992
• Status: Expired due to Fees

• Current Assignee: Australian Nuclear Science & Technology Organisation (Government of Australia)
• Original Assignee: Australian Nuclear Science & Technology Organisation (Government of Australia)
• Inventors: Kojima, Masaharu, Jackson, Timothy W., Lambrecht, Richard M.
• Primary Examiner(s): Wu, Shean
• Assistant Examiner(s): KELLEY, LARA CHAPMAN
• Application Number:
  US08/097,403
• Time in Patent Office: 953 Days
• Field of Search: 534/10, 424/1.65, 424/1.69, 424/1.29
• US Class Current: 424/1.65
• CPC Class Codes: C07C 323/25 the carbon skeleton being acyclic and saturated
• CPC Class Codes: C07F 13/005 Compounds without a metal-carbon linkage

Abstract

Rhenium complexes of formula (I), radiolabelled complexes thereof or pharmaceutically acceptable salts thereof: ##STR1## wherein R is straight or branched chain C_1-10 alkyl, C_1-10 alkenyl, C_1-10 alkynyl optionally substituted by cycloalkyl or aryl; C_1-10 cycloalkyl optionally substituted by straight or branched chain alkyl, alkenyl, alkynyl or aryl; or aryl optionally substituted by straight or branched chain alkyl, alkenyl, alkynyl or cycloalkyl for use in liver cancer therapy and metastasis of cancer.

Claims

1. A product comprising a rhenium complex of formula (I):

##STR5## wherein the rhenium atom is radioactive, or a pharmaceutically acceptable salt

wherein R is straight or branched chain C_1-10 alkyl, C_1-10 alkenyl, C_1-10 alkynyl optionally substituted by C_5-6 cycloalkyl or phenyl;

C_5-6 cycloalkyl optionally substituted by straight or branched chain alkyl, alkenyl, alkynyl or phenyl;

or phenyl optionally substituted by straight or branched chain alkyl, alkenyl, alkynyl or C_5-6 cycloalkyl; and

a lipid soluble oil selected from the group consisting of iodized poppyseed oil.

2. A product according to claim 1 further comprising the anti-cancer agent SMANCS.

5. The product of claim 1, wherein R is straight or branched chain C₅, C₇, or C₉ alkyl.

11. The product of claim 1, wherein R is straight or branched chain C₅ alkyl.

12. The product of claim 2, wherein R is straight or branched chain C₅, C₇, or C₉ alkyl.

13. The product of claim 2, wherein R is straight or branched chain C₅ alkyl.

3. A product comprising a rhenium complex of formula (I):

##STR6## wherein the rhenium atom is radioactive, or a pharmaceutically acceptable salt thereof;

wherein R is straight or branched chain C_1-10 alkyl, C_1-10 alkenyl, C_1-10 alkynyl optionally substituted by C_5-6 cycloalkyl or phenyl;

C_5-6 cycloalkyl optionally substituted by straight or branched chain alkyl, alkenyl, alkynyl or phenyl;

or phenyl optionally substituted by straight or branched chain alkyl, alkenyl, alkynyl or C_5-6 cycloalkyl; and

LIPIODOL (iodized poppyseed oil, 38% w/w iodine).

4. The product of claim 3, further comprising the anti-cancer agent SMANCS.

14. The product of claim 3, wherein R is straight or branched chain C₅, C₇, or C₉ alkyl.

15. The product of claim 3, wherein R is straight or branched chain C₅ alkyl.

16. The product of claim 4, wherein R is straight or branched chain C₅, C₇, or C₉ alkyl.

17. The product of claim 4, wherein R is straight or branched chain C₅ alkyl.

6. A method of enhancing the efficacy of iodized poppy seed oil in the treatment of liver cancer in a subject which comprises administering to said subject a formulation containing a rhenium complex of formula (I):

##STR7## wherein the rhenium atom is radioactive, or a pharmaceutically acceptable salt thereof;

wherein R is straight or branched chain C_1-10 alkyl, C_1-10 alkenyl, C_1-10 alkynyl optionally substituted by C_5-6 cycloalkyl or phenyl;

C_5-6 cycloalkyl optionally substituted by straight or branched chain alkyl, alkenyl, alkynyl or phenyl;

or phenyl optionally substituted by straight or branched chain alkyl, alkenyl, alkynyl or C_5-6 cycloalkyl; and

iodized poppyseed oil.

9. The method of claim 6, wherein R is straight or branched chain, C₅, C₇, or C₉ alkyl.

18. The method of claim 6, wherein R is straight or branched chain C₅ alkyl.

7. A method of treatment or prophylaxis of liver cancer and metastasis of cancer is a subject comprising administering to the subject a formulation containing a rhenium complex of formula (I):

##STR8## wherein the rhenium atom is radioactive, or a pharmaceutically acceptable salt thereof;

wherein R is straight or branched chain C_1-10 alkyl, C_1-10 alkenyl, C_1-10 alkynyl optionally substituted by C_5-6 cycloalkyl or phenyl;

C_5-6 cycloalkyl optionally substituted by straight or branched chain alkyl, alkenyl, alkynyl or phenyl;

or phenyl optionally substituted by straight or branched chain alkyl, alkenyl, alkynyl or C_5-6 cycloalkyl; and

wherein the radioactive rhenium complex of formula (I) is administered in combination with iodized poppyseed oil.

8. A method according to claim 7 wherein the rhenium complex of formula (I) and iodized poppyseed oil are administered in combination with the anti-cancer agent SMANCS.

10. The method of claim 7, wherein R is straight or branched chain C₅, C₇, or C₉ alkyl.

19. The method of claim 7, wherein R is straight or branched chain C₅ alkyl.

20. The method of claim 8, wherein R is straight or branched chain C₅, C₇, or C₉ alkyl.

21. The method of claim 8, wherein R is straight or branched chain C₅ alkyl.