The present invention includes pharmaceutical composition comprising (2R,2R)-3,3-disulfanediyl bis(2-acetamidopropanamide)(diNACA) or D.sub.3-N-acetyl cysteine amide, or a physiologically acceptable salt thereof, having a deuterium enrichment above the natural abundance of deuterium, and derivatives or solids thereof, and methods of using diNACA to treat eye diseases and other diseases associated with oxidative damage including, e.g., antivenom, beta-thallassemia, cataract, chronic obstructive pulmonary disease, macular degeneration, contrast-induced nephropathy, asthma, lung contusion, methamphetamine-induced oxidative stress, multiple sclerosis, Parkinson's disease, platelet apoptosis, Tardive dyskinesia, Alzheimer disease, HIV-1-associated dementia, mitochondrial diseases, myocardial myopathy, neurodegenerative diseases, pulmonary fibrosis, skin pigmentation, skin in need of rejuventation, antimicrobial infection, Friedreich's ataxia.

The present invention includes pharmaceutical composition comprising (2R,2R)-3,3-disulfanediyl bis(2-acetamidopropanamide)(diNACA) or D.sub.3-N-acetyl cysteine amide, or a physiologically acceptable salt thereof, having a deuterium enrichment above the natural abundance of deuterium, and derivatives or solids thereof, and methods of using diNACA to treat eye diseases and other diseases associated with oxidative damage including, e.g., antivenom, beta-thallassemia, cataract, chronic obstructive pulmonary disease, macular degeneration, contrast-induced nephropathy, asthma, lung contusion, methamphetamine-induced oxidative stress, multiple sclerosis, Parkinson's disease, platelet apoptosis, Tardive dyskinesia, Alzheimer disease, HIV-1-associated dementia, mitochondrial diseases, myocardial myopathy, neurodegenerative diseases, pulmonary fibrosis, skin pigmentation, skin in need of rejuventation, antimicrobial infection, Friedreich's ataxia.

Compounds represented by structural formulas described herein, such as Structural Formula (I):

##STR00001##

or a pharmaceutically acceptable salt thereof are useful in treating conditions such as metal overload, oxidative stress, and neoplastic and preneoplastic conditions.

Compounds represented by structural formulas described herein, such as Structural Formula (I):

##STR00001##

or a pharmaceutically acceptable salt thereof are useful in treating conditions such as metal overload, oxidative stress, and neoplastic and preneoplastic conditions.

Iron overload is associated with pathological conditions such as oxidative stress, transfusional iron overload, thalassemia, primary hemochromatosis, secondary hemochromatosis, diabetes, liver disease, heart disease, cancer, radiation injury, neurological or neurodegenerative disorder, Friedreich's ataxia (FRDA), macular degeneration, closed head injury, irritable bowel disease, and reperfusion injury. The present invention provides methods and pharmaceutical compositions using desferrithiocin analogs of Formulae (A) and (J) for treating and/or preventing these pathological conditions, metal (e.g., iron, aluminum, a lanthanide, or an actinide (e.g., uranium)) overload conditions, and infectious diseases (e.g., malaria).

Iron overload is associated with pathological conditions such as oxidative stress, transfusional iron overload, thalassemia, primary hemochromatosis, secondary hemochromatosis, diabetes, liver disease, heart disease, cancer, radiation injury, neurological or neurodegenerative disorder, Friedreich's ataxia (FRDA), macular degeneration, closed head injury, irritable bowel disease, and reperfusion injury. The present invention provides methods and pharmaceutical compositions using desferrithiocin analogs of Formulae (A) and (J) for treating and/or preventing these pathological conditions, metal (e.g., iron, aluminum, a lanthanide, or an actinide (e.g., uranium)) overload conditions, and infectious diseases (e.g., malaria).

Compounds represented by structural formulas described herein, such as Structural Formula (I): ##STR00001##
or a pharmaceutically acceptable salt thereof are useful in treating conditions such as metal overload, oxidative stress, and neoplastic and preneoplastic conditions.

Compounds represented by structural formulas described herein, such as Structural Formula (I): ##STR00001##
or a pharmaceutically acceptable salt thereof are useful in treating conditions such as metal overload, oxidative stress, and neoplastic and preneoplastic conditions.

The present invention provides compounds of Formula (I), which are metabolically programmed metal chelators, e.g., lipophilic, absorbable (e.g., orally absorbable), and effective metal chelators that are converted in vivo to their hydrophilic, nontoxic metabolites. The present invention also provides compounds of Formula (II), which are also metabolically programmed metal chelators. The invention also provides pharmaceutical compositions, kits, methods, and uses that include a compound described herein. The compounds, pharmaceutical compositions, kits, and methods may be useful in treating or preventing a disease (e.g., metal overload, oxidative stress, diabetes, liver disease, heart disease, cancer, radiation injury, neurological or neurodegenerative disorder, Friedreich's ataxia (FRDA), macular degeneration, closed head injury, irritable bowel disease, reperfusion injury, metal poisoning, or infectious disease).

The present invention provides compounds of Formula (I), which are metabolically programmed metal chelators, e.g., lipophilic, absorbable (e.g., orally absorbable), and effective metal chelators that are converted in vivo to their hydrophilic, nontoxic metabolites. The present invention also provides compounds of Formula (II), which are also metabolically programmed metal chelators. The invention also provides pharmaceutical compositions, kits, methods, and uses that include a compound described herein. The compounds, pharmaceutical compositions, kits, and methods may be useful in treating or preventing a disease (e.g., metal overload, oxidative stress, diabetes, liver disease, heart disease, cancer, radiation injury, neurological or neurodegenerative disorder, Friedreich's ataxia (FRDA), macular degeneration, closed head injury, irritable bowel disease, reperfusion injury, metal poisoning, or infectious disease).