This invention relates to inhibitors of mitotic kinesins, particularly KSP, and methods for producing these inhibitors.

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Provided are novel compounds containing a polymeric carbohydrate backbone, one or more mannose-binding C-type lectin receptor targeting moieties, and a nitrogenous bisphosphonate compound coupled to the backbone via a thiol-maleimide conjugation, in addition to pharmaceutical compositions, methods of synthesizing, and methods of use. The thiol-maleimide conjugation of a bisphosphonate to a polymeric carbohydrate backbone provides for methods of using the compounds and compositions thereof for releasing the therapeutic payload when internalized into a mannose-binding C-type lectin receptor-expressing cell, such as tumor associated macrophages (TAMs) for the treatment of various diseases, including, cancer, autoimmune diseases, and inflammatory disorders.

The present invention relates to phosphate derivatives of formula (I), and their therapeutic uses, preferably for treating a respiratory disease. The present invention further relates to pharmaceutical compositions and devices comprising such compounds.

The present invention relates to phosphate derivatives of formula (I), and their therapeutic uses, preferably for treating a respiratory disease. The present invention further relates to pharmaceutical compositions and devices comprising such compounds.

This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a 2-hydroxybenzoic acid structure which function as sirtuin (e.g., SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, SIRT7) inhibitors and/or degraders which function as effective therapeutic agents for treating, ameliorating, and preventing disorders associated with sirtuin activity (e.g., melanoma, Ewing sarcoma, malignant peripheral nerve sheath tumor, non-small cell lung cancer). In addition, this invention also relates to a new class of proteolysis-targeting chimeras (PROTACs) (as defined herein) which function as sirtuin inhibitors and/or degraders within cancer and/or immune cells. Pharmaceutical compositions comprising said compounds are also within the scope of the present invention.

This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a 2-hydroxybenzoic acid structure which function as sirtuin (e.g., SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, SIRT7) inhibitors and/or degraders which function as effective therapeutic agents for treating, ameliorating, and preventing disorders associated with sirtuin activity (e.g., melanoma, Ewing sarcoma, malignant peripheral nerve sheath tumor, non-small cell lung cancer). In addition, this invention also relates to a new class of proteolysis-targeting chimeras (PROTACs) (as defined herein) which function as sirtuin inhibitors and/or degraders within cancer and/or immune cells. Pharmaceutical compositions comprising said compounds are also within the scope of the present invention.

Disclosed herein are embodiments of compounds that can be used to target glutathione to various target sites, such as cells, mitochondria, and other organelles. Also disclosed herein are embodiments of methods for making and using the compounds. In particular disclosed embodiments, the compounds can be used to treat, ameliorate, and/or prevent diseases or conditions associated with low or reduced glutathione levels, as well as other types of diseases/conditions.

Disclosed herein are embodiments of compounds that can be used to target glutathione to various target sites, such as cells, mitochondria, and other organelles. Also disclosed herein are embodiments of methods for making and using the compounds. In particular disclosed embodiments, the compounds can be used to treat, ameliorate, and/or prevent diseases or conditions associated with low or reduced glutathione levels, as well as other types of diseases/conditions.

The present inventors have shown that specific benzene sulfonamide thiazole compounds (I) have the ability to induce an early endoplasmic reticulum stress. These compounds also lead to cancerous cells growth inhibition and death.

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The present inventors have shown that specific benzene sulfonamide thiazole compounds (I) have the ability to induce an early endoplasmic reticulum stress. These compounds also lead to cancerous cells growth inhibition and death.

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