The present disclosure relates to prodrugs, double prodrugs, derivatives and analogues of 3-(methylamino)-2-((methylamino)methyl)propane-1-thiol. The compounds of this disclosure also relate to ##STR00001##
The use of these compounds as radio— and chemo—protectors is also described.

The present invention is directed to a compound of Formula (I) or a pharmaceutically acceptable salt thereof. Compounds of Formula (I) are CD38 inhibitors, which can be used to treat a disease or condition in a subject that benefits from an increase in NAD.sup.+ or to treat a mitochondrial disorder in a subject. Such disease or condition is a muscle structure disorder, a neuronal activation disorder, a muscle fatigue disorder, a muscle mass disorder, a metabolic disease, a cancer, a vascular disease, an ocular vascular disease, a muscular eye disease, or a renal disease. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 30 to 135; examples 1 to 61; table). Such an exemplary compound is e.g. N-((1r,4r)-4-(2-methoxyethoxy) cyclohexyl)-5-(thiazol-5-yl)-1H-indole-7-carboxamide (II).

##STR00001##

The present disclosure is drawn to a method of treating a patient in need of treatment, comprising identifying a patient in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia; administering a bolus of glyburide to the patient; and administering a continuous infusion of glyburide to the patient at from about 15 μg/hr and about 300 μg/hr, wherein the continuous infusion glyburide is administered for a period of time more than about 20 hours.

The present invention relates, inter alia, to a method comprising administering to a subject having high output shock and undergoing treatment with a catecholamine at a dose equivalent to at least about 0.2 mcg/kg/min of norepinephrine a dose of angiotensin II which is effective to raise the blood pressure of the subject to a mean arterial pressure (MAP) of about 65 mm Hg or above, and which is effective to reduce the dose of the catecholamine required to maintain a MAP of about 65 mm Hg to the equivalent of about 0.05-0.2 mcg/kg/min norepinephrine or less, or to the equivalent of about 0.05 mcg/kg/min norepinephrine or less.

The present invention relates, inter alia, to a method comprising administering to a subject having high output shock and undergoing treatment with a catecholamine at a dose equivalent to at least about 0.2 mcg/kg/min of norepinephrine a dose of angiotensin II which is effective to raise the blood pressure of the subject to a mean arterial pressure (MAP) of about 65 mm Hg or above, and which is effective to reduce the dose of the catecholamine required to maintain a MAP of about 65 mm Hg to the equivalent of about 0.05-0.2 mcg/kg/min norepinephrine or less, or to the equivalent of about 0.05 mcg/kg/min norepinephrine or less.

Disclosed herein are new therapeutic methods comprising administering compounds that can stabilize HIF and inhibit HIF prolyl hydroxylase (HIF-PH). In particular, methods described herein can be useful for treating/preventing a disease or condition in patients in need thereof, such as a patient having a viral infection such as a respiratory and/or pulmonary viral infection (e.g., an infection such as COVID-19 or a coronavirus infection). Methods described herein can also be useful for treating/preventing organ injury (e.g. organ injury that occurs concurrently or as a result of an infection). For example, methods described herein can be useful for treating or preventing acute lung injury, acute respiratory distress syndrome (ARDS), cardiovascular injury, injury to the liver, kidney diseases, and/or multi-organ failure.

Disclosed herein are new therapeutic methods comprising administering compounds that can stabilize HIF and inhibit HIF prolyl hydroxylase (HIF-PH). In particular, methods described herein can be useful for treating/preventing a disease or condition in patients in need thereof, such as a patient having a viral infection such as a respiratory and/or pulmonary viral infection (e.g., an infection such as COVID-19 or a coronavirus infection). Methods described herein can also be useful for treating/preventing organ injury (e.g. organ injury that occurs concurrently or as a result of an infection). For example, methods described herein can be useful for treating or preventing acute lung injury, acute respiratory distress syndrome (ARDS), cardiovascular injury, injury to the liver, kidney diseases, and/or multi-organ failure.

Methods of treating anti-inflammatory conditions through the use of boron-containing small molecules are disclosed.

Provided herein are ready-to-use premixed pharmaceutical compositions of nicardipine or a pharmaceutically acceptable salt and methods for use in treating cardiovascular and cerebrovascular conditions.

The present disclosure provides a method of treating cardiometabolic syndrome (CMS) with a GDF15 molecule. Also provided herein is a method of treating a cardiac or heart condition. In some embodiments, the GDF15 molecule is a GDF15-Fc fusion, in which a GDF15 region is fused to an Fc region, optionally via a linker.