Method for the treatment of ischemic disease and reperfusion injury and the prevention of the adverse effects of reactive oxygen species
AssigneeBoard of Regents of the University of Colorado
InventorLawrence D. Horwitz
Life of this patent
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Abstract
Bucillamine and N-2,2-dimethyl-3-mercaptopropionyl)-L-cysteine or related compounds can be used to prevent damage to living tissue from the formation or presence of reactive oxygen species. These reactive oxygen species are formed when tissue is first rendered hypoxic due to interruption of blood flow and then reoxygenated by restoration of blood flow. In particular, the invention is directed to the administration of bucillamine and N-2,2-dimethyl-3-mercaptopropionyl)-L-cysteine prior to or coincidental with reperfusion to prevent damage to myocardium from formation of reactive oxygen species. Also presented are application of these compounds to similar ischemia-related cell injury in other organs.
Claims20
A method for the treatment of ischemic diseases or other conditions involving injury to mammalian tissue by reactive oxygen species which comprises administering an effective amount of a compound of the following general formula or a pharmaceutically acceptable salt thereof together with pharmaceutically acceptable carriers:
- ##STR5## wherein:
- R.sup.1 and R.sup.2, independently of one another, are lower alkyl groups;
- R.sup.3 is a carboxyl group which can be converted into an ester or amide;
- R.sup.4 is selected from the group consisting of a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a phenyl-lower alkyl group or a phenylcarbonyl group, and the phenyl ring in the phenyl-lower alkyl and phenylcarbonyl groups can be substituted by at least one selected from halogen atoms, and lower alkyl, hydroxy, lower alkoxy, lower alkylenedioxy, nitro, amino and lower alkylamino groups;
- R.sup.5 represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a phenyl-lower alkyl group or a phenylcarbonyl group, and the phenyl ring in the phenyl-lower alkyl and phenylcarbonyl groups can be substituted by at least one selected from halogen atoms, and lower alkyl, hydroxy, lower alkoxy, lower alkylenedioxy, nitro, amino and lower alkylamino groups;
- "n" is an integer that is 0 or 1;
- and
- "A" is a lower alkylene group.
A method of protecting live mammalian tissue from injury resulting from exposure to reactive oxygen species comprising administration of a pharmaceutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof along with pharmaceutically acceptable carriers ##STR6## wherein:
- R.sup.1 and R.sup.2, independently of one another, are lower alkyl groups;
- R.sup.3 is a carboxyl group which can be converted into an ester or amide;
- R.sup.4 is selected from the group consisting of a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a phenyl-lower alkyl group or a phenylcarbonyl group, and the phenyl ring in the phenyl-lower alkyl and phenylcarbonyl groups can be substituted by at least one selected from halogen atoms, and lower alkyl, hydroxy, lower alkoxy, lower alkylenedioxy, nitro, amino and lower alkylamino groups;
- R.sup.5 represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a phenyl-lower alkyl group or a phenylcarbonyl group, and the phenyl ring in the phenyl-lower alkyl and phenylcarbonyl groups can be substituted by at least one selected from halogen atoms, and lower alkyl, hydroxy, lower alkoxy, lower alkylenedioxy, nitro, amino and lower alkylamino groups;
- "n" is an integer that is 0 or 1;
- and
- "A" is a lower alkylene group.
Dependencies are inferred from the claim text.