Oxidant scavengers
AssigneesDuke University, University of Alabama at Birmingham Research Foundation, Aeolus Pharmaceuticals, Inc.
InventorsJames D. Crapo, Irwin Fridovich, Tim Oury, Brian J. Day, Rodney J. Folz, Bruce A. Freeman, Michael P. Trova, Ines Batinic-Haberle
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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.
Claims6
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.
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.
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.
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.
Dependencies are inferred from the claim text.