Synthetic catalytic free radical scavengers useful as antioxidants for prevention and therapy of disease

• US 7,582,786 B2
• Filed: 02/23/2006
• Issued: 09/01/2009
• Est. Priority Date: 12/07/1992
• Status: Expired due to Fees

• Current Assignee: Eukarion, Inc.
• Original Assignee: Eukarion, Inc.
• Inventors: Doctrow, Susan Robin, Malfroy-Camine, Bernard
• Primary Examiner(s): Nazario Gonzalez; Porfirio
• Application Number:
  US11/362,454
• Publication Number:
  US 20060149089A1
• Time in patent office: 1,286 Days
• Field of Search: 556/34, 556/35, 514/492, 514/499, 514/501, 514/502, 514/505
• US Class Current: 556/34
• CPC Class Codes: C07F 13/005 Compounds without a metal-carbon linkage

Abstract

The invention provides antioxidant salen-metal complexes, compositions of such antioxidant salen-metal complexes having superoxide activity, catalase activity, and/or peroxidase activity, compositions of salen-metal complexes in a form suitable for pharmaceutical administration to treat or prevent a disease associated with cell or tissue damage produced by free radicals such as superoxide, and cosmetic and free radical quenching formulations of salen metal compounds.

Claims

1. A salen-metal compound having antioxidant activity and having a structural formula of Structure XXIII or Structure XXIV as shown in FIG. 26E, wherein:

M is selected from the group consisting of Mn, Co, Fe, V, and Cr;

A is an axial ligand selected from the group consisting of Cl, F, O, Br and acetyl;

X₂, X₃ and X₄ are independently selected from the group consisting of hydrogen, lower alkoxy, halide and aryloxy;

Y₂, Y₃ and Y₄ are independently selected from the group consisting of hydrogen, lower alkoxy, halide and aryloxy; and

R₁, R₂, R₃ and R₄ are independently selected from the group consisting of hydrogen, aryl, substituted aryl, heteroatom-bearing aromatic, arylalkyl, lower alkoxy and halide and wherein one of R₁ and R₂ is optionally covalently linked to one of R₃ and R₄ thereby forming a cyclic structure.

2. The salen-metal compound of claim 1 having a structural formula of Structure XXIII as shown in FIG. 26E.

3. The salen-metal compound of claim 1 having a structural formula of Structure XXIV as shown in FIG. 26E.

4. The salen-metal compound of claim 1 wherein M is Mn.

5. The salen-metal compound of claim 1 wherein the axial ligand is selected from the group consisting of Cl and acetyl.

6. The salen-metal compound of claim 5 wherein the axial ligand is an acetyl group.

7. The salen-metal compound of claim 5 wherein the axial ligand is chloride.

8. The salen-metal compound of claim 1 wherein X₂, X₃, X₄, Y₂, Y₃ and Y₄ are each hydrogen.

9. The salen-metal compound of claim 1 wherein R₁, R₂, R₃ and R₄ are independently hydrogen.

10. The salen-metal compound of claim 1 wherein one of R₁ and R₂ is covalently linked to one of R₃ and R₄ thereby forming a cyclic structure.

11. The salen-metal compound of claim 10 wherein the cyclic structure is a six-membered ring.

12. The salen-metal compound of claim 11 wherein said compound has the structure of compound C82 shown in FIG. 24G.

13. The salen-metal compound of claim 1 wherein said compound has superoxide dismutase activity.

14. The salen-metal compound of claim 1 wherein said compound has catalase activity.

15. The salen-metal compound of claim 1 wherein said compound has peroxidase activity.

16. The salen-metal compound of claim 1 wherein said compound has superoxide dismutase activity and catalase activity and peroxidase activity.

17. A pharmaceutically acceptable composition comprising a salen-metal compound of claim 1 and an excipient or carrier.

18. The pharmaceutically acceptable composition of claim 17 in the form of a tablet, capsule, ampule, inhalable composition, suppository, or injectable composition.

19. A method of inhibiting damage to cells induced by reactive oxygen species comprising contacting cells having oxidative stress with a salen-metal compound of claim 1.

20. A method of treating free radical-associated disease comprising administering to a subject a therapeutically-effective dose of the pharmaceutically acceptable composition of claim 17.