A composition and method of treatment of neuromuscular, neuromuscular degenerative, neurodegenerative, autoimmune, developmental, traumatic, hearing loss related, and/or metabolic diseases, including spinal muscular atrophy (SMA) syndrome (SMA1, SMA2, SMA3, and SMA4, also called Type I, II, III and IV), traumatic brain injury (TBI), concussion, keratoconjunctivitis sicca (Dry Eye Disease), glaucoma, Sjogren's syndrome, rheumatoid arthritis, post-LASIK surgery, anti-depressants use, Wolfram Syndrome, and Wolcott-Rallison syndrome. The composition is selected from the group consisting of 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP, bipartite 2,3-dinitrophenol, 2,4-dinitrophenol, 2,5-dinitrophenol, 2,6-dinitrophenol, 3,4-dinitrophenol, or 3,5-dinitrophenol (2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP) prodrugs; Gemini prodrugs, bioprecursor molecules, and combinations thereof. A dose of the composition for treatment of neurodegenerative diseases may be from about 0.01 mg/kg of body weight to about 50 mg/kg of body weight of the patient in need of treatment. A dose of the composition for treatment of metabolic diseases may be from about 1 mg/70 kg of body weight to about 100 mg/70 kg of body weight of the patient in need of treatment, and a maximum dose per day is about 200 mg/70 kg of body weight of the patient in need of treatment.

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

A preparation method for a halogen-substituted compound is provided, where a piperazine derivative shown in formula I reacts with a halogenated acetyl halide derivative shown in formula VI to generate a halogen-substituted compound shown in formula II. The present invention further relates to a preparation method for preparing a pyrazole derivative by using a halogen-substituted compound, where a halogen-substituted compound shown in formula II reacts with methylhydrazine to close a pyrazole ring, to generate a halogen-substituted alkyl-1-methylpyrazole derivative shown in formula IV, or reacts with methylhydrazine benzaldehyde hydrazone to generate a hydrazone compound shown in formula III, which closes, under the action of an acid, a pyrazole ring to generate a halogen-substituted alkyl-1-methylpyrazole derivative shown in formula IV. The present invention further relates to a structure of an intermediate compound. The preparation methods for a halogen-substituted compound and a pyrazole derivative are suitable for industrial production.

Aspects of the present invention are directed to structurally modified opioids (SMOs) that result in improved modulating activity at the NMDAR and improved PK and PD parameters over existing drugs with NMDAR modulating activity. The structural modifications of an opioid or opioid enantiomer that result in the SMOs can be obtained by starting the synthetic process de novo; by modifying the synthetic process for the opioid at any intermediate step during the synthesis of the racemate or of one enantiomer; or by modifying the structure of the opioid or opioid enantiomer after the synthesis. The nitric acid ester substitutions are of particular relevance, especially when associated to deuterated substitutions and/or halogen substitutions.

This application provides a lithium-ion battery and an apparatus. The lithium-ion battery includes an electrode assembly and an electrolyte. The electrode assembly includes a positive electrode plate, a negative electrode plate, and a separator. A positive active material of the positive electrode plate includes Li.sub.x1Co.sub.y1M.sub.1-y1O.sub.2-z1Q.sub.z1, where 0.5≤x1≤1.2, 0.8≤y1<1.0, 0≤z1≤0.1, M is selected from one or more of Al, Ti, Zr, Y, and Mg, and Q is selected from one or more of F, Cl, and S. The electrolyte contains an additive A that is a polynitrile six-membered nitrogen-heterocyclic compound with a relatively low oxidation potential. The lithium-ion battery has superb cycle performance and storage performance, especially under high-temperature and high-voltage conditions.

This application provides a lithium-ion battery and an apparatus. The lithium-ion battery includes an electrode assembly and an electrolyte. The electrode assembly includes a positive electrode plate, a negative electrode plate, and a separator. A positive active material of the positive electrode plate includes Li.sub.x1Co.sub.y1M.sub.1-y1O.sub.2-z1Q.sub.z1, where 0.5≤x1≤1.2, 0.8≤y1<1.0, 0≤z1≤0.1, M is selected from one or more of Al, Ti, Zr, Y, and Mg, and Q is selected from one or more of F, Cl, and S. The electrolyte contains an additive A that is a polynitrile six-membered nitrogen-heterocyclic compound with a relatively low oxidation potential. The lithium-ion battery has superb cycle performance and storage performance, especially under high-temperature and high-voltage conditions.

Provided herein are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders associated with HDAC1 and/or HDAC2 activity.

Provided herein are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders associated with HDAC1 and/or HDAC2 activity.

The present invention generally relates to the field of radiopharmaceuticals and their use in nuclear medicine as tracers, imaging agents and for the treatment of various disease states of prostate cancer. Thus, the present invention concerns compounds that are represented by the general Formulae (Ia) or (Ib).