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

• US 5,403,834 A
• Filed: 12/07/1992
• Issued: 04/04/1995
• Est. Priority Date: 12/07/1992
• Status: Expired due to Term

• Current Assignee: Eukarion, Inc.
• Original Assignee: Eukarion, Inc.
• Inventors: Baudry, Michel, Malfroy-Camine, Bernard
• Primary Examiner(s): Henley, III, Raymond
• Assistant Examiner(s): CRIARES, THEODORE J
• Application Number:
  US07/987,474
• Time in Patent Office: 848 Days
• Field of Search: 514/185
• US Class Current: 514/185
• CPC Class Codes: A61K 31/28 Compounds containing heavy metals
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07F 13/005 Compounds without a metal-carbon linkage

Abstract

The invention provides antioxidant 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.

Claims

1. A pharmaceutical composition comprising a therapeutically effective dose of an antioxidant salen-metal complex in a pharmaceutically acceptable form, wherein the antioxidant salen-metal complex has the structural formula ##STR15## wherein M is manganese;

A is H or halogen;

n is 0, 4, 5, or 6, wherein Cn is absent if n=0 and is a saturated hydrocarbon chain if n=4, 5, or 6;

R₁ and R₄ are independently selected from the group consisting of H, phenyl, lower alkoxy, and lower fatty acid esters;

X₁ and X₃ are independently selected from the group consisting of H, lower alkyl, amine, lower alkylamino, and halogen;

X₂ and X₄ are H;

Y₁ and Y₄ are independently selected from the group consisting of H, lower alkyl, halogen, and lower alkoxy;

Y₂, Y₃, Y₅ and Y₆ are H; and

all remaining substituent positions are H.

2. A pharmaceutical composition according to claim 1 wherein the antioxidant salen-metal complex is selected from the group consisting of:

##STR16##

3. A pharmaceutical composition comprising a therapeutically effective dose of an antioxidant salen-metal complex in a pharmaceutically acceptable form, wherein the antioxidant salen-metal complex is selected from the group consisting of:

##STR17##

5. A pharmaceutical composition according to claim 3, wherein the antioxidant salen-metal complex is the SOD-mimetic ##STR19##

6. A pharmaceutical composition according to claim 5, wherein the pharmaceutical composition comprises at least 10 mg of ##STR20## in a form suitable for parenteral administration.

4. A pharmaceutical composition comprising a therapeutically effective dose of an antioxidant salen-metal complex in a pharmaceutically acceptable form, wherein the antioxidant salen-metal complex is selected from the group consisting of:

##STR18##