Disclosed in the present invention are a substituted nitrogen heterocyclic compound and anesthetic action thereof. Specifically provided a chemical compound as shown in formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, a prodrug thereof, a metabolite thereof or a deuterated derivative thereof. The substituted nitrogen heterocyclic compound provided in the present application has good central nervous system inhibition effects, capable of generating sedative, hypnotic and/or general anesthetic effects, and capable of controlling status epilepticus; said substituted nitrogen heterocyclic compound is also characterized by rapid onset of action and rapid recovery, while maintaining positive anesthetic activity; in addition, said substituted nitrogen heterocyclic compound has almost no inhibitory effect on adrenocortical function, low side effects, and resolves technical difficulties in the art. The present invention provides a new selection for clinical screening and/or preparation of sedative, hypnotic and/or general anesthetic drugs and drugs controlling status epilepticus.

Disclosed in the present invention are a substituted nitrogen heterocyclic compound and anesthetic action thereof. Specifically provided a chemical compound as shown in formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, a prodrug thereof, a metabolite thereof or a deuterated derivative thereof. The substituted nitrogen heterocyclic compound provided in the present application has good central nervous system inhibition effects, capable of generating sedative, hypnotic and/or general anesthetic effects, and capable of controlling status epilepticus; said substituted nitrogen heterocyclic compound is also characterized by rapid onset of action and rapid recovery, while maintaining positive anesthetic activity; in addition, said substituted nitrogen heterocyclic compound has almost no inhibitory effect on adrenocortical function, low side effects, and resolves technical difficulties in the art. The present invention provides a new selection for clinical screening and/or preparation of sedative, hypnotic and/or general anesthetic drugs and drugs controlling status epilepticus.

Compounds of formula (1) comprising a pleuromutilin backbone with a triazole based side-group at C22 are provided. The compounds can be used for treatment of bacterial infections and fungal infections. Importantly, infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) may be treated effectively.

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Compounds of formula (1) comprising a pleuromutilin backbone with a triazole based side-group at C22 are provided. The compounds can be used for treatment of bacterial infections and fungal infections. Importantly, infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) may be treated effectively.

##STR00001##

The present invention provides compounds useful as inhibitors of ATP citrate lyase (ACLY), compositions thereof, and methods of using the same.

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain embodiments, modulators are derivatives of hexahydropentalene. In certain embodiments, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein.

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain embodiments, modulators are derivatives of hexahydropentalene. In certain embodiments, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein.

A self-assembled therapeutic dendron-micelle includes a first amphiphilic dendron-coil, a second amphiphilic dendron-coil, and optionally a third amphiphilic dendron-coil, and an encapsulated BRD4 ligand or BRD4 proteolysis targeting chimera. The first and optional third amphiphilic dendron-coils have a therapeutic peptide conjugated thereto. Also included are pharmaceutical compositions containing the dendron-micelles, methods of making the dendron-micelles, and therapeutic methods including administering the dendron-micelles to a subject in need thereof.

The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.