Oxidant scavengers

• US 6,583,132 B1
• Filed: 11/30/1998
• Issued: 06/24/2003
• Est. Priority Date: 10/15/1993
• Status: Expired due to Term

• Current Assignee: Goodnow Capital, L.L.C.
• Original Assignee: Aeolus Pharmaceuticals, Inc., Duke University, The University Of Alabama At Birmingham Research Foundation
• Inventors: Day, Brian J., Crapo, James D., Freeman, Bruce A., Folz, Rodney J., Oury, Tim, Fridovich, Irwin, Trova, Michael P., Batinic-Haberle, Ines
• Primary Examiner(s): Weddington, Kevin E.
• Application Number:
  US09/201,722
• Time in Patent Office: 1,667 Days
• Field of Search: 514/185
• US Class Current: 514/185
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol

Abstract

The present invention relates, in general, to a method of modulating physiological and pathological processes and, in particular, to a method of modulating intra- and extracellular levels of oxidants and thereby processes in which such oxidants are a participant. The invention also relates to compounds and compositions suitable for use in such methods.

Claims

1. A method of treating a pathological condition of a patient resulting from degradation of NO·

or a biologically active form thereof comprising administering to said patient an effective amount of a compound having the activity of a catalytic antioxidant under conditions such that said treatment is effected.

2. The method according to claim 1 wherein said biologically active form of NO·

is a nitroso, thiol, nitrosyl, NO⁺ or NO<sup>−

group.</sup>

4. The method according to claim 1 or 3 wherein said compound is a porphyrin ring-containing compound.

3. A method of treating a pathological condition of a patient resulting from peroxynitrite accumulation comprising administering to said patient an effective amount of a compound having the activity of a catalytic antioxidant under conditions such that said treatment is effected.

5. A method of modulating NO·

function as a neurotransmitter in a mammal comprising contacting said mammal with an amount of an oxidant scavenger of the formula,

or a pharmaceutically acceptable salt thereof wherein;

R₁ is a bond,

wherein X is a halogen and Y is an alkyl group and wherein

indicates bonding to R₂ at any position and

indicates bonding to R₂ and the substituent at any position; and

R₂ is a bond, —

(CY′

₂)_n⁻

, —

(CY′

₂—

CY′

=CY′

)_n⁻

, —

(CY′

₂—

Y′

₂—

CH=CH)_n⁻

, —

(CY′

=CY′

)_n⁻

, or

wherein Y′

is hydrogen or an alkyl group and wherein n is 1 to 8; and

R₃ is —

Y″

, —

OH, —

NH₂, —

N⁻

(Y″

)₃, —

COOH, —

COO⁻

, —

SO₃H, —

SO₃⁻

, —

C—

PO₃H₂ or —

C—

POO₃H⁻

, where Y″

is an alkyl group, optionally complexed with a metal selected from the group consisting of manganese, copper and iron, sufficient to effect said modulation.

6. A method of modulating NO·

function as a neurotransmitter in a mammal comprising contacting said mammal with an amount of an oxidant scavenger of the formula,

or a pharmaceutically acceptable salt thereof, or metal complex thereof wherein said metal is selected from the group consisting of manganese, copper and iron, wherein;

each R₁′

is independently a bond,

wherein Y″

is an alkyl group, and wherein

indicates bonding to R₃′

at any position and

indicates bonding to R₂′ and

the R₁′

phenyl substituent at any position;

each R₂′

is independently a bond, or —

(CH₂ )_n—

wherein n is 1-4,

each R₃′

is independently —

Y″

, —

Y′

″

, —

H, —

OH, —

OY″

, —

NO₂, —

CN, —

NH₂, —

COOH, —

COY″

, —

COO⁻

, or a heterocyclic group wherein Y″

is as defined above and Y′

″

is a primary, secondary, tertiary or quaternary amine,

wherein when R₁′

is

R₃′

is not COOH, COY″

or COO⁻

,

wherein when R₁′

is

R₃′

is not —

NO₂, and

wherein —

R₁′

—

R₂′

—

R₃′

, collectively, are not —

H, sufficient to effect said modulation.