Galectin-3 inhibiting c-glycosides
Inventors
Magnani, John L. • Peterson, John M. • Sarkar, Arun K. • VOHRA, Yusufbhai U. • Ghosh, Indranath • NOGUEIRA, Jason
Assignees
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Publication Number
US-11873317-B2
Publication Date
2024-01-16
Expiration Date
Abstract
Compounds, compositions, and methods for treatment and/or prevention of at least one disease, disorder, and/or condition by inhibiting binding of galectin-3 to ligands are disclosed. For example, inhibitors of galectin-3 are described and pharmaceutical compositions comprising at least one such agent is described.
Core Innovation
The invention relates to compounds chosen from compounds of Formula (I), including pharmaceutically acceptable salts and prodrugs of Formula (I). The compounds are characterized by variable substituents R1, R2, R3, X, and Y, with further optional substitution patterns and ring-closure options, defining a broad chemical scope for galectin-related antagonist candidates and Gal-3 inhibitory agents.
The invention positions the compounds and pharmaceutical compositions for inhibiting galectin-3 binding to ligands, including by acting at the CRD of galectin-3 and interfering with galectin-3/ligand interactions. It further describes use in treating and preventing diseases associated with galectin-3 activity, with related contexts including inflammatory disease, fibrosis, cancer, metastasis, cell infiltration into marrow/bone, thrombosis, cardiovascular/atherosclerosis, pathological angiogenesis, neurodegeneration including alpha-synucleinopathies, mobilization/retention of immune cells, and checkpoint inhibition of T-cells.
The partial content also identifies exemplified galectin-3 antagonist candidates within the Formula (I) framework and states an evaluation context for galectin-3 through an ELISA assay with IC50 values tabulated for selected compound numbers. The document thereby connects the defined Formula (I) variability to specific compound instances and measured Galectin-3 activity.
Claims Coverage
The provided independent claims center on Formula (I) compounds with broad substituent definitions and pharmaceutically acceptable salts and prodrugs. The claim set also extends to therapeutic use contexts, including cancer treatment and inhibition of cancer cell infiltration, and to galectin-3-related compound embodiments.
Formula (I) compound scaffold with variable substituents
At least one compound chosen from compounds of Formula (I) and pharmaceutically acceptable salts and prodrugs thereof, wherein R1, R2, R3, X, and Y are defined by extensive substituent selections and optional substitutions, including ring-closure options.
Cancer treatment with chemotherapy and/or radiotherapy
A method of treating cancer by administering to a subject an effective amount of at least one compound of the Formula (I) claim framework together with at least one of chemotherapy or radiotherapy.
Inhibition of cancer cell infiltration into specified body sites
A method of inhibiting cancer cell infiltration into liver, lymph nodes, lung, bone, or bone marrow by administering an effective amount of at least one compound.
Specific galectin-3 inhibitor claim framework
A Formula (I) galectin-3 inhibitor compound selection with variable substituents R1, R2, R3, X, and Y, including prodrugs of Formula (I) and pharmaceutically acceptable salts.
Overall claim coverage is centered on Formula (I) compounds defined by variable substituents R1, R2, R3, X, and Y, with dependent claim contexts for cancer treatment, inhibition of cancer cell infiltration, and galectin-3 inhibitor compound selections.
Stated Advantages
The compounds are presented as an approach to overcome low activity and/or specificity and stability and absorption issues associated with natural galectin-3 ligands.
Documented Applications
Inflammatory disease use via galectin-3 inhibition.
Fibrosis use via galectin-3 inhibition.
Cancer use via galectin-3 inhibition, including metastasis and cell infiltration into marrow/bone.
Mobilization/retention of immune cells via galectin-3 inhibition.
Checkpoint inhibition of T-cells via galectin-3 inhibition.
Thrombosis use via galectin-3 inhibition.
Cardiovascular/atherosclerosis use via galectin-3 inhibition.
Pathological angiogenesis use via galectin-3 inhibition.
Neurodegenerative disease use via galectin-3 inhibition, including alpha-synucleinopathies.
Pharmaceutical compositions comprising Formula (I).
Methods for treating cancer by administering an effective amount of at least one compound together with chemotherapy and/or radiotherapy.
Methods for inhibiting cancer cell infiltration into liver, lymph nodes, lung, bone, or bone marrow by administering an effective amount of at least one compound.
Galectin-3 activity assessment in an ELISA assay with IC50 values tabulated for selected compound numbers.
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