Desferrithiocin polyether analogues

• US 9,567,309 B2
• Filed: 07/28/2015
• Issued: 02/14/2017
• Est. Priority Date: 04/04/2005
• Status: Active Grant

• Current Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Original Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Inventors: Bergeron, Raymond J. Jr.
• Primary Examiner(s): Stockton, Laura L.
• Application Number:
  US14/811,598
• Publication Number:
  US 20150336911A1
• Time in Patent Office: 567 Days
• Field of Search: 548/201
• US Class Current: 1/1
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• 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 39/04 Chelating agents
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07D 277/10 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 277/12 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms

Abstract

Compounds represented by structural formulas described herein, such as Structural Formula (I):

or a pharmaceutically acceptable salt thereof are useful in treating conditions such as metal overload, oxidative stress, and neoplastic and preneoplastic conditions.

Claims

1. A method of treating transfusional iron overload in a subject, comprising administering to the subject a therapeutically or prophylactically effective amount of a compound of the formula:

2. The method of claim 1, wherein the compound is of Formula (I):

3. The method of claim 2, wherein R₉ is —

OR₁₂;

R₈ is —

H or —

CH₃;

R₆ and R₇ are independently —

H or —

CH₃; and

R₃, R₄, and R₅ are each —

H.

4. The method of claim 3, wherein R₂ is —

[(CH₂)_n—

O]_x—

R′

;

n is 1 to 4; and

x is 1 to 4.

5. The method of claim 1, wherein the compound is of the formula:

7. The method of claim 2, wherein carbon atom labeled with “

*”

is of the S-configuration.

8. The method of claim 2, wherein carbon atom labeled with “

*”

is of the R-configuration.

9. The method of claim 1, wherein R₉ is —

OR₁₂.

10. The method of claim 9, wherein R₈ is —

H.

11. The method of claim 9, wherein R₈ is —

CH₃.

12. The method of claim 9, wherein R₆ and R₇ are —

H.

13. The method of claim 9, wherein R₆ and R₇ are —

CH₃.

14. The method of claim 9, wherein R₃, R₄, and R₅ are —

H.

15. The method of claim 9, wherein R₂ is —

[(CH₂)_n—

O]_x—

R′

;

n is independently 1 to 4; and

x is 1 to 4.

16. The method of claim 9, wherein R₁ is —

H.

17. The method of claim 1, wherein the pharmaceutically acceptable salt is an alkali metal salt or alkaline earth metal salt.

18. The method of claim 1, wherein the pharmaceutically acceptable salt is a sodium salt, potassium salt, magnesium salt, or calcium salt.

21. The method of claim 9, wherein R₁₂ is —

H.

22. The method of claim 9, wherein R₁₂ is an alkyl group.

23. The method of claim 9, wherein R₁₂ is a C_1-6 alkyl group.

24. The method of claim 1, wherein each n is 2.

25. The method of claim 1 comprising administering to the subject a therapeutically effective amount of the compound.

6. A method of treating transfusional iron overload in a subject, comprising administering to the subject a therapeutically or prophylactically effective amount of a compound of Formula (VI):

19. The method of claim 6, wherein the pharmaceutically acceptable salt is an alkali metal salt or alkaline earth metal salt.

20. The method of claim 6, wherein the pharmaceutically acceptable salt is a sodium salt, potassium salt, magnesium salt, or calcium salt.

26. The method of claim 6 comprising administering to the subject a therapeutically effective amount of the compound.