Heterocyclic derivatives, pharmaceutical compositions and their use in the treatment or amelioration of cancer
Inventors
FLÜCKIGER-MANGUAL, Stefanie • Gruber, Dorothea • FOLMER, Rutger • Hekking, Koen F. W. • Veerman, Johan J. N. • Eerland, Martijn • Fabritius, Charles-Henry
Assignees
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Publication Number
US-12478624-B2
Publication Date
2025-11-25
Expiration Date
Abstract
The present invention relates to a compound of formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, cocrystal, tautomer, racemate, enantiomer, or diastereomer or mixture thereof: formula (I) and to pharmaceutical compositions comprising a compound of formula (I), as well as to the use of a compound of formula (I), or a pharmaceutically acceptable salt, solvate, cocrystal, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, in the treatment of cancer. Further aspects of the present invention include combination therapies in which a compound of formula (I), as well as to the use of a compound of formula (I), or a pharmaceutically acceptable salt, solvate, cocrystal, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, is used in combination with a known anti-cancer agent.
Core Innovation
The invention relates to compounds of formula (I), or pharmaceutically acceptable salts, solvates, cocrystals, tautomers, racemates, enantiomers, diastereomers, or mixtures thereof. The compounds are defined by extensive structural selections for R1, R21, R3, X1, X2, X3, R31, E, and R6x within the formula (I) scaffold, including heterocyclyl, carbocyclyl, alkylene-linked heterocyclyl or carbocyclyl, and heteroatom-containing hydrocarbon groups.
R1 is selected from halogen and unsubstituted or substituted hydrocarbon groups with specified carbon and heteroatom limits. R21 is selected from hydrogen, unsubstituted or substituted C1-6 alkyl, unsubstituted or substituted C1-6 alkyl containing one to three oxygen atoms between carbon atoms, and unsubstituted or substituted C3-6 cycloalkyl. R3 is selected from unsubstituted or substituted heterocyclyl, unsubstituted or substituted carbocyclyl, and alkylene-linked heterocyclyl or carbocyclyl options.
At least one of X1, X2 and X3 is N, where each of X1, X2 and X3 is independently selected from N, CH and CRx. E is either absent or selected from CH2-, CHRx-, CRx2-, NH-, NRx-, O-, and L1-L2 or L2-L1 combinations with L1 and L2 selected from the listed linkers. R31 is selected from hydrogen, C1-6 alkyl, and C1-6 alkyl substituted with one or more F, and R3 and any R31 are separate substituents or linked with each other.
Claims Coverage
The consolidated claim coverage is centered on one compound of Formula (I) and extends to pharmaceutical composition and cancer-treatment method coverage. In total, three independent claim groups are identified: a Formula (I) compound, a pharmaceutical composition, and a method of treating or ameliorating cancer.
Compound of formula (I) with defined substituent framework
A compound of formula (I), or a pharmaceutically acceptable salt, solvate, cocrystal, tautomer, racemate, enantiomer, diastereomer, or mixture thereof, wherein R1, R21, R3, X1, X2, X3, R31, E, and R6x are selected according to the specified structural constraints.
Pharmaceutical composition with excipients or carriers
A pharmaceutical composition comprising a compound of formula (I) together with one or more pharmaceutically acceptable excipients or carriers.
Cancer treatment by administering a therapeutically effective amount
A method for treating or ameliorating cancer by administering to a patient a therapeutically effective amount of a compound of formula (I).
Combination therapy with a second anti-cancer agent
The cancer-treatment method includes administering the compound together with a second therapeutic agent that is an anti-cancer agent.
Treatment directed to enumerated cancer types
The method is directed to cancer types selected from the listed cancers, including melanoma and non-small cell lung cancer, and other enumerated cancers.
The claim coverage is grounded in a Formula (I) compound with detailed structural definitions for R1, R21, R3, X1/X2/X3, R31, E, and R6x, and is extended to pharmaceutical compositions and cancer-treatment methods, including combination therapy and treatment of enumerated cancer types.
Stated Advantages
The enantiomers corresponding to formula (Va) and (Vb) are significantly more active than other enantiomers or diastereomers.
The compounds are stated to address durable anti-tumor effect and overcoming resistance to kinase inhibitors, including EGFR inhibitors.
Documented Applications
Treating or ameliorating cancer by administering a therapeutically effective amount of a compound of formula (I).
Combination therapy for cancer by administering the compound together with a second therapeutic agent that is an anti-cancer agent.
Treating cancer types selected from the listed cancers, including melanoma, non-small cell lung cancer, prostate cancer, bile duct cancer, bladder cancer, pancreatic cancer, thyroid cancer, ovarian cancer, colorectal tumor, hairy cell leukemia, acute myeloid leukemia, multiple myeloma, liver cancer, breast cancer, esophageal cancer, head and neck cancer, and glioma.
Pharmaceutical composition use in cancer treatment, including formulation with pharmaceutically acceptable excipient(s) and carrier(s).
Preventing or delaying drug resistance.
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