Desferrithiocin polyether analogues
Inventors
Assignees
University of Florida • National Institutes of Health NIH • University of Florida Research Foundation Inc • US Department of Health and Human Services
Publication Number
US-8278458-B2
Publication Date
2012-10-02
Expiration Date
2026-03-22
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Compounds represented by structural formulas described herein, such as Structural Formula (I): or a pharmaceutically acceptable salt thereof are useful in treating conditions such as metal overload, oxidative stress, and neoplastic and preneoplastic conditions.
Core Innovation
The invention relates to compounds represented by specific structural formulas, including Structural Formulas (I), (II), and (III), and their pharmaceutically acceptable salts, solvates, or hydrates. These compounds are useful in treating conditions such as metal overload, oxidative stress, and neoplastic or preneoplastic conditions. The invention also includes pharmaceutical compositions containing these compounds for use in therapy and methods of treating subjects by administering effective amounts of these compounds or compositions.
The background explains that primates have an efficient iron recycling process without a specific mechanism for eliminating excess iron, which can lead to chronic overload and biological damage. Iron overload, introduced via diet, acute ingestion, or transfusions, is typically treated by phlebotomy, but this is not feasible in cases like chronic transfusion therapy for aplastic anemia and thalassemia. Current iron chelators, such as desferrioxamine B, have limitations including poor oral activity and inefficiency, and many synthetic chelators and siderophores have unacceptable toxicity or lack oral activity. Therefore, there remains a need for novel iron chelators that offer efficient chelation, suitable oral bioavailability, and minimal toxicity.
The summary emphasizes that the invention provides compounds characterized by defined structural formulas that can effectively chelate trivalent metals, including iron. These compounds exhibit desirable iron clearing efficiency, potentially different biodistribution allowing penetration into organs such as the heart, brain, and pancreas, and favor clearance through the liver, reducing kidney toxicity. The compounds can be administered via various routes, preferably orally, and may be used to treat metal overload conditions, reduce oxidative stress, and treat neoplastic or preneoplastic diseases.
Claims Coverage
The patent includes independent claims covering compounds represented by Structural Formula (I), pharmaceutical compositions containing these compounds, and methods of treating trivalent metal overload using these compounds. The main inventive features focus on the chemical structures and their therapeutic applications.
Compound represented by Structural Formula (I)
A compound characterized by Structural Formula (I) with specific substituents and defined parameters such as R9 being —OR12, R8 being —H or —CH3, and R3, R4, R5, R6, and R7 each being —H, along with additional structural details reflecting polyether substitution and related features.
Pharmaceutical composition comprising the compound
A pharmaceutical composition that includes the compound of Structural Formula (I) together with a pharmaceutically acceptable carrier or diluent, where the compound has specific substituents as outlined in the compound claims.
Method of treating trivalent metal overload
A method of treatment involving administering a therapeutically effective amount of a compound represented by Structural Formula (I) for the treatment of trivalent metal overload conditions including iron and aluminum overload, with the compound having specified structural features and dosing parameters.
The independent claims encompass the chemical compounds with specified structural formulas and substitutions, pharmaceutical compositions containing these compounds, and therapeutic methods using these compounds to treat trivalent metal overload conditions, particularly iron overload, including association with hemochromatosis.
Stated Advantages
The metal chelators of the invention have a desirable iron clearing efficiency.
These chelators possess a different volume of distribution resulting in distinct organ distribution, including penetration into the heart, brain, and pancreas.
The compounds show predominant clearance through the liver, reducing the risk of kidney toxicity.
Compounds exhibit low concentration in the kidneys following administration, enhancing safety.
Documented Applications
Treatment of pathological conditions responsive to chelation or sequestration of trivalent metals, including iron overload and aluminum overload.
Reducing oxidative stress in subjects, including those suffering from ischemic episodes or inflammatory disorders.
Treating neoplastic diseases and preneoplastic conditions encompassing a wide variety of tumors and cancers.
Use as contrast agents for medical imaging or examining organs and tissues.
Interested in licensing this patent?