An object of the present invention is to provide a compound that has a specific chemical structure having an activation effect on SIRT6 and is useful as an active component for preventing and treating inflammatory diseases, and the present invention relates to a compound represented by Formula (1) or a pharmaceutically acceptable salt thereof,

##STR00001## where each symbol in Formula (1) has the same definition as that described in the specification.

Disclosed is a use of recombinant human neuregulin derivatives in preparing a medicine for preventing, treating, or reducing the progression of cardiovascular diseases in mammals. In particular, the present invention relates to a novel recombinant human NRG-FC protein and a use thereof in the treatment of cardiovascular diseases. The protein has a prolonged half-life and enhanced biological activity.

The disclosure relates to methods for treating acute respiratory distress syndrome (ARDS), acute lung inflammation (ALI), acute lung injury and/or cardiac injury (e.g., acute cardiac injury), treating an infection, reducing pathogen burden and/or inhibiting pathogen replication by administering to a subject in need thereof a therapeutically effective amount of an aldose reductase inhibitor. In some aspects, the subject is infected with a respiratory pathogen and has influenza, SARS, MERS or COVID-19.

The disclosure relates to methods for treating acute respiratory distress syndrome (ARDS), acute lung inflammation (ALI), acute lung injury and/or cardiac injury (e.g., acute cardiac injury), treating an infection, reducing pathogen burden and/or inhibiting pathogen replication by administering to a subject in need thereof a therapeutically effective amount of an aldose reductase inhibitor. In some aspects, the subject is infected with a respiratory pathogen and has influenza, SARS, MERS or COVID-19.

Described herein are compounds of Formula I,

##STR00001##

wherein R.sup.1, R.sup.2, and R.sup.3 are defined herein, their use as branched-chain alpha keto acid dehydrogenase kinase inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, diabetes, NASH and heart failure.

Described herein are compounds of Formula I,

##STR00001##

wherein R.sup.1, R.sup.2, and R.sup.3 are defined herein, their use as branched-chain alpha keto acid dehydrogenase kinase inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, diabetes, NASH and heart failure.

Compositions for intravenous infusion of istaroxime, or a metabolite of istaroxime, in human patients suffering from heart failure are disclosed. Likewise, methods for extended infusion of istaroxime or its metabolites in individuals with heart failure are disclosed. In particular, some methods disclosed herein include the infusion of istaroxime, or a metabolite thereof, for a period of time that is greater than six hours in order to improve cardiac relaxation without triggering arrhythmogenic events in an individual suffering from heart failure. Other methods include administration of istaroxime until certain plasma concentration thresholds of istaroxime metabolites are achieved. Also disclosed are istaroxime metabolites with selective SERCA2a activation.

Compositions for intravenous infusion of istaroxime, or a metabolite of istaroxime, in human patients suffering from heart failure are disclosed. Likewise, methods for extended infusion of istaroxime or its metabolites in individuals with heart failure are disclosed. In particular, some methods disclosed herein include the infusion of istaroxime, or a metabolite thereof, for a period of time that is greater than six hours in order to improve cardiac relaxation without triggering arrhythmogenic events in an individual suffering from heart failure. Other methods include administration of istaroxime until certain plasma concentration thresholds of istaroxime metabolites are achieved. Also disclosed are istaroxime metabolites with selective SERCA2a activation.

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification. The compounds are apelin and APJ agonists for treating cardiovascular diseases. Preferred compounds are 2-(1,1′-biphe-1H-benzo[d]imidazole derivatives. The invention further provides compositions comprising the compounds and the compounds for use in methods of medical treatment. ##STR00001##

A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a disintegrant, a surfactant, a binder, and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Processes of preparing pharmaceutical compositions comprising Compound 1 are also disclosed.