This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit (e.g., antagonize) Stimulator of Interferon Genes (STING). Said chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) STING activation (e.g., STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions containing the same as well as methods of using and making the same.

This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit (e.g., antagonize) Stimulator of Interferon Genes (STING). Said chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) STING activation (e.g., STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions containing the same as well as methods of using and making the same.

The invention relates to a prodrug compound of levosimendan as shown by the formula below, and solvates, hydrates, N-oxides, stereoisomers, and pharmaceutically acceptable salts thereof, wherein each of Ra and Rb is selected from hydrogen or C1-C6 alkyl; Rp is selected from a basic group containing N atom or an acidic group containing carboxyl group, phosphate group, sulfate group, and sulfonate group. The prodrug compound overcomes the defects of levosimendan such as poor water solubility, and has an ideal pharmacokinetic profile and excellent prospects for medicament development. ##STR00001##

The invention relates to a prodrug compound of levosimendan as shown by the formula below, and solvates, hydrates, N-oxides, stereoisomers, and pharmaceutically acceptable salts thereof, wherein each of Ra and Rb is selected from hydrogen or C1-C6 alkyl; Rp is selected from a basic group containing N atom or an acidic group containing carboxyl group, phosphate group, sulfate group, and sulfonate group. The prodrug compound overcomes the defects of levosimendan such as poor water solubility, and has an ideal pharmacokinetic profile and excellent prospects for medicament development. ##STR00001##

Disclosed are small molecules against cereblon to enhance effector T cell function. Methodos of making thes molecules and methods of using them to treat various disease states are also disclosed.

A P2Y12 receptor antagonist containing a guanidyl, and a preparation method and the use thereof. In particular, the present disclosure provides a pyridazinone-guanidine compound that is a compound of structural formula (I), or a stereoisomer of the above-mentioned compound, a pro-drug thereof, a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof. Such a compound has multiple pharmacological activities, especially has an inhibitory effect on platelet aggregation, and can be used for preparing an anti-platelet aggregation pharmaceutical composition.

A P2Y12 receptor antagonist containing a guanidyl, and a preparation method and the use thereof. In particular, the present disclosure provides a pyridazinone-guanidine compound that is a compound of structural formula (I), or a stereoisomer of the above-mentioned compound, a pro-drug thereof, a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof. Such a compound has multiple pharmacological activities, especially has an inhibitory effect on platelet aggregation, and can be used for preparing an anti-platelet aggregation pharmaceutical composition.

A method for producing 6-oxo-1,4,5,6-tetrahydropyridazine-3 -carboxylic acid is disclosed that includes steps of adding hydrazine sulfate with 2-ketoglutaric acid in a container as a solid, adding water to the solid creating a heterogenous mixture of the hydrazine sulfate, 2-ketoglutaric acid and water, blending the heterogenous mixture for at least one hour, and measuring the heterogenous mixture to confirm that it has converted into 6-oxo-1,4,5,6-tetrahydropyridazine-3-carboxylic acid. Hydrazine sulfate can be added to the 2-ketoglutaric acid in the container at a ratio of greater than 1.1. The compound 6-oxo-1,4,5,6-tetrahydropyridazine-3-carboxylic acid (PCA) has many uses. It has been used for medical applications and as a building block and for medical applications. The compound is also a product of the remediation of hydrazine using 2-ketogluraric acid.

A method for producing 6-oxo-1,4,5,6-tetrahydropyridazine-3 -carboxylic acid is disclosed that includes steps of adding hydrazine sulfate with 2-ketoglutaric acid in a container as a solid, adding water to the solid creating a heterogenous mixture of the hydrazine sulfate, 2-ketoglutaric acid and water, blending the heterogenous mixture for at least one hour, and measuring the heterogenous mixture to confirm that it has converted into 6-oxo-1,4,5,6-tetrahydropyridazine-3-carboxylic acid. Hydrazine sulfate can be added to the 2-ketoglutaric acid in the container at a ratio of greater than 1.1. The compound 6-oxo-1,4,5,6-tetrahydropyridazine-3-carboxylic acid (PCA) has many uses. It has been used for medical applications and as a building block and for medical applications. The compound is also a product of the remediation of hydrazine using 2-ketogluraric acid.

Substituted pyridazinone compounds, conjugates, and pharmaceutical compositions for use in the treatment of neuromuscular diseases, such as Duchenne Muscular Dystrophy (DMD), are disclosed herein. The disclosed compounds are useful, among other things, in the treating of DMD and modulating inflammatory inhibitors IL-1, IL-6 or TNF-α.