Compounds for treatment of cancer
Inventors
Li, Wei • Xiao, Min • Dalton, James • Ahn, Sunjoo • MILLER, Duane D • Wang, Jin
Assignees
University of Tennessee Research Foundation • Oncternal Therapeutics Inc
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Publication Number
US-11084811-B2
Publication Date
2021-08-10
Expiration Date
Abstract
The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.
Core Innovation
The invention relates to treating cervical cancer in a subject in need thereof by administering a therapeutically effective amount of a compound having the structure of formula XI. In formula XI, X is a bond or NH, Q is NH or S in one embodiment, and A is a substituted or unsubstituted single-, fused- or multiple-ring (hetero)cyclic ring system, including saturated or unsaturated N-heterocycles, S-heterocycles, O-heterocycles, cyclic hydrocarbons, and mixed heterocycles.
The A ring is optionally substituted by 1-5 substituents selected from O-alkyl, O-haloalkyl, halogens, CN, —CH2CN, NH2, hydroxyl, —OC(O)CF3, C1-C5 linear or branched alkyl, haloalkyl, alkylamino, aminoalkyl, —OCH2Ph, —NHCO-alkyl, COOH, —C(O)Ph, C(O)O-alkyl, C(O)H, —C(O)NH2, or NO2, including groups of the forms —(CH2)iNHCH3, —(CH2)iNH2, and —(CH2)iN(CH3)2 where i is an integer between 0-5. The compounds further include isomers, pharmaceutically acceptable salts, pharmaceutical products, tautomers, hydrates, N-oxides, or combinations thereof.
The document also provides embodiments tied to specific formula variants such as XI(e), XI(b), and XI(c), and mentions named compounds including compound 17ya and compound 55. In addition, the disclosed method includes embodiments in which the compound is administered as part of a pharmaceutical composition with a pharmaceutically acceptable carrier and embodiments in which another cancer therapy is further administered.
Claims Coverage
The independent claims comprise two cervical-cancer treatment methods. The inventive features center on formula XI compounds with defined X and Q variables, a substituted or unsubstituted ring system A with enumerated substituents, and permitted pharmaceutically acceptable forms; the second independent claim also includes the integer parameter i.
Treating cervical cancer with formula XI compounds where X is a bond and Q is NH
A method of treating cervical cancer in a subject in need thereof comprising administering a therapeutically effective amount of a compound having the structure of formula XI, wherein X is a bond, Q is NH, and A is a substituted or unsubstituted single-, fused- or multiple-ring (hetero)cyclic ring system optionally substituted by 1-5 substituents selected from an enumerated list, together with an isomer, pharmaceutically acceptable salt, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof.
Treating cervical cancer with formula XI compounds where X is NH and Q is NH or S
A method of treating cervical cancer in a subject in need thereof comprising administering a therapeutically effective amount of a compound having the structure of formula XI, wherein X is NH, Q is NH or S, and A is a substituted or unsubstituted single-, fused- or multiple-ring (hetero)cyclic ring system optionally substituted by 1-5 substituents selected from an enumerated list, including groups of the forms —(CH2)iNHCH3, —(CH2)iNH2, and —(CH2)iN(CH3)2, where i is an integer between 0-5, together with an isomer, pharmaceutically acceptable salt, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof.
The claims are directed to administering therapeutically effective amounts of formula XI compounds for treating cervical cancer, with coverage defined by the X and Q assignments, the A-ring substituent scope, and the inclusion of pharmaceutically acceptable forms. Dependent claims further narrow to specific formula variants and named compounds, and may add pharmaceutical composition context or further administration of another cancer therapy.
Stated Advantages
The disclosure frames a need to improve properties such as solubility in the context of anti-cancer activity.
Documented Applications
Treating cervical cancer in a subject in need thereof by administering a therapeutically effective amount of a compound having the structure of formula XI.
Anticancer applications, including cervical cancer.
Administration as part of a pharmaceutical composition with a pharmaceutically acceptable carrier.
Further administration of another cancer therapy in combination with the compound treatment.
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