Glycosylated histone deacetylase inhibitors and methods of making and using the same
Inventors
Oyelere, Adegboyega • Tapadar, Subhasish • Wu, Bocheng
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12617813-B2
Publication Date
2026-05-05
Expiration Date
Abstract
Provided herein are glycosylated compounds as histone deacetylase (HDACi) inhibitors or a diastereomer, solvate, or a pharmaceutically acceptable salt thereof. Also provided are pharmaceutical compositions and medicaments that include the compounds described herein as well as methods of treating inflammatory disease and cancer.
Core Innovation
The invention describes compounds of Formula I, including glycosylated and mannosylated triazole hydroxamate histone deacetylase inhibitors, or diastereomers, solvates, and pharmaceutically acceptable salts thereof. These compounds incorporate sugar moieties linked through aryl or 1,2,3-triazole-containing scaffolds to zinc-binding groups, such as hydroxamates or N-(2-aminophenyl)acylamides. The disclosure also provides pharmaceutical compositions comprising these compounds for histone deacetylase inhibition and the treatment of inflammatory diseases and various cancers.
The reported findings demonstrate cell-growth inhibition, histone deacetylase target engagement, apoptosis, and cell-cycle effects in Hep-G2 cells, alongside limited apoptosis in Vero cells. Evaluated compounds induce increased acetylated tubulin, elevated histone H4, and caspase-3 activation, with cytotoxicity showing attenuation via GLUT2 blockade. The specific problem addressed in the background section is not explicitly described in the patent text.
Claims Coverage
The claims identify one independent claim directed to compounds of Formula I, encompassing one core inventive feature alongside dependent claims covering structural refinements, pharmaceutical compositions, histone deacetylase inhibition, and treatment methods.
Compound of formula I
Claim 1 recites a compound of Formula I with specified alternatives for X, R1–R5, A, B, C, D, and ZBG, wherein X is O or NCH3; R1, R2, R3, and R4 have specified alternatives; Y is O; A is substituted or unsubstituted aryl; B is absent or 1,2,3-triazolyl; C is C2-8 alkyl, optionally substituted with one or more double bonds; D has specified alternatives; and ZBG is selected as recited in the claim, or a diastereomer, solvate, or pharmaceutically acceptable salt thereof.
The independent claim centers on the defined Formula I compounds, diastereomers, solvates, or pharmaceutically acceptable salts thereof, which serve as histone deacetylase inhibitors for compositions and therapeutic treatments.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Inhibition of histone deacetylases, including contacting histone deacetylase cells with the compound or a pharmaceutical composition thereof.
Treatment of cancers, including hepatocellular cancer, liver cancer, cholangiocarcinoma, non-small cell lung cancer, lung adenocarcinoma, squamous cell lung cancer, small-cell lung cancer, and breast cancer.
Treatment of inflammatory diseases, including inflammatory bowel disease.
Interested in licensing this patent?