Oxindole compounds and pharmaceutical compositions thereof
Inventors
Beeson, Craig C. • LINDSEY, Christopher C. • Rohrer, Baerbel • Peterson, Yuri Karl
Assignees
MUSC Foundation for Research and Development • US Department of Veterans Affairs
Publication Number
US-10370328-B2
Publication Date
2019-08-06
Expiration Date
2036-04-28
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Abstract
Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of degenerative diseases and disorders.
Core Innovation
The invention provides compounds of formula (I) and their pharmaceutically acceptable salts, along with pharmaceutical compositions containing these compounds. These compounds protect against calcium- and oxidative-stress mediated damage to mitochondrial functions and are useful for treating degenerative diseases and disorders. The invention also includes methods of using these compounds for such treatments.
The problem addressed is the damage and dysfunction of mitochondria, organelles responsible for cellular energy production, due to reactive oxygen species (ROS) and calcium overload. Such mitochondrial impairment contributes to a range of degenerative diseases, including retinal degenerative diseases, neurodegenerative disorders, and other conditions associated with oxidative stress and mitochondrial DNA mutations. Current treatments using vitamins and metabolic cofactors have limited general utility, highlighting a need for new drugs with improved safety, efficacy, or physical properties to treat these mitochondrial-related degenerative diseases.
Claims Coverage
The patent contains one independent claim defining a set of specific oxindole compounds and a pharmaceutical composition containing them. The main inventive features cross chemical structure definitions and formulation claims.
Specific oxindole compounds
The invention covers a plurality of specifically enumerated oxindole compounds or their pharmaceutically acceptable salts, each represented by detailed chemical names.
Pharmaceutical compositions
Compositions comprising a therapeutically effective amount of at least one compound according to the invention or a pharmaceutically acceptable salt thereof, combined with a pharmaceutically acceptable carrier.
The independent claims define the invention as specific oxindole compounds with particular substituents and their use in pharmaceutical compositions for treatment purposes.
Stated Advantages
The compounds protect against calcium- and oxidative-stress mediated damage to mitochondrial functions.
The compounds are useful for the treatment of degenerative diseases and disorders.
The compounds mitigate oxidative- and calcium-mediated loss of mitochondrial capacity in cell lines.
They protect photoreceptors from cell death in several models of retinal degeneration.
Documented Applications
Treatment of degenerative diseases including retinal degenerative diseases such as retinitis pigmentosa.
Treatment of neurodegenerative disorders, such as Parkinson's, Alzheimer's, and Huntington's Diseases.
Prevention of calcium-induced or oxidant-induced mitochondrial damage and loss of mitochondrial respiratory capacity in susceptible cells.
Therapeutic use in models of retinal degeneration including mouse models (rd1, rd10) and light-induced retinal damage models resembling age-related macular degeneration.
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