Therapeutically active compounds and their methods of use
Inventors
Konteatis, Zenon D. • Popovici-Muller, Janeta • Travins, Jeremy M. • Zahler, Robert • Cai, Zhenwei • Zhou, Ding
Assignees
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Publication Number
US-12433895-B2
Publication Date
2025-10-07
Expiration Date
Abstract
Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.
Core Innovation
The disclosed subject matter provides substituted triazine and pyrimidine compounds, including di-aliphatic 1,3,5-triazine-2,4-diamines of Formula (Ia) and related subgenera, stereoisomers, pharmaceutically acceptable salts, and hydrates. These mutant-IDH inhibitor compounds encompass variations in ring A selected from phenyl, pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, thiazolyl, oxazolyl, and isoxazolyl groups, with fluorinated or cycloalkyl substituents subject to structural provisos. Representative compound synthesis and characterization provide experimental support for the disclosed chemical genus.
The disclosure describes methods for treating diseases associated with mutant IDH1 or IDH2, particularly cancers characterized by the presence of an isocitrate dehydrogenase 1 (IDH1) mutation. These methods comprise administering a therapeutically effective amount of a Formula (Ia) compound, a specified formula compound, or a pharmaceutical composition comprising the compound and pharmaceutically acceptable excipients. The background links mutant IDH activity to the production of the oncogenic metabolite 2-hydroxyglutarate.
Claims Coverage
The claims identify three independent claims directed to three inventive features for treating cancer characterized by an IDH1 mutation.
Treatment of cancer using a Formula (Ia) compound
Administering to a patient in need thereof a therapeutically effective amount of a compound having Formula (Ia), or a pharmaceutically acceptable salt or hydrate thereof, to treat cancer characterized by an IDH1 mutation, wherein ring A is selected from phenyl, pyrazolyl, oxazolyl, isoxazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and thiazolyl, subject to defined substituents and structural provisos.
Treatment of cancer using a specified formula compound
Administering to a patient in need thereof a therapeutically effective amount of a compound having the specified claimed Formula, or a pharmaceutically acceptable salt or hydrate thereof, to treat cancer characterized by an IDH1 mutation.
Treatment of cancer using a pharmaceutical composition
Administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a claimed compound, or a pharmaceutically acceptable salt or hydrate thereof, and one or more pharmaceutically acceptable excipients, to treat cancer characterized by an IDH1 mutation.
The independent claims cover methods for treating IDH1-mutation-characterized cancer through administration of a defined Formula (Ia) compound, a specified formula compound, or a pharmaceutical composition comprising a claimed compound and pharmaceutically acceptable excipients.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treatment of cancers driven by mutant IDH1 or IDH2, including mutation-specific applications such as mutant IDH1 R132X (including R132H and R132C), IDH2 R140X, and IDH2 R172X.
Treatment of 2-hydroxyglutaric aciduria, Maffucci syndrome, and Ollier disease.
Combination therapy for cancer, including administration of a second therapeutic agent useful for treating cancer, and monitoring treatment through 2-hydroxyglutarate (2HG) levels.
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