A61K31/665

Gold (I)-Phosphine Compounds as Anti-Bacterial Agents

A compound of formula (I): for use in the prevention or treatment of a bacterial infection wherein: A is either S or Se; RA is selected from: wherein: each of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.9 is independently selected from CH or N, wherein at least three of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.9 is CH; V is selected from O, CH—OR.sup.01, N—CO.sub.2—R.sup.C2 or N—R.sup.N2; one of Y.sup.5, Y.sup.6, Y.sup.7 and Y.sup.8 is selected from CH and N, and the others are CH; X is selected from NH, S or O; R.sup.C1 is selected from O—R.sup.O2 or NHR.sup.N1; R.sup.O1 is selected from H and C.sub.1-3 unbranched alkyl; R.sup.O2 is C.sub.1-3 unbranched alkyl; R.sup.N1 is selected from H and C.sub.1-3 unbranched alkyl; R.sup.N2 is C.sub.1-3 unbranched alkyl; R.sup.C2 is either C.sub.1-3 unbranched alkyl or C.sub.3-4 branched alkyl; R.sup.C3 is selected from C.sub.1-3 unbranched alkyl and C.sub.2H.sub.4CO.sub.2H; R.sup.C4 is either H or Me; R.sup.C5 is either H or Me; R.sup.C6 represents one or two optional methyl substituents; and n is an integer from 2 to 8.

##STR00001##

Gold (I)-Phosphine Compounds as Anti-Bacterial Agents

A compound of formula (I): for use in the prevention or treatment of a bacterial infection wherein: A is either S or Se; RA is selected from: wherein: each of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.9 is independently selected from CH or N, wherein at least three of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.9 is CH; V is selected from O, CH—OR.sup.01, N—CO.sub.2—R.sup.C2 or N—R.sup.N2; one of Y.sup.5, Y.sup.6, Y.sup.7 and Y.sup.8 is selected from CH and N, and the others are CH; X is selected from NH, S or O; R.sup.C1 is selected from O—R.sup.O2 or NHR.sup.N1; R.sup.O1 is selected from H and C.sub.1-3 unbranched alkyl; R.sup.O2 is C.sub.1-3 unbranched alkyl; R.sup.N1 is selected from H and C.sub.1-3 unbranched alkyl; R.sup.N2 is C.sub.1-3 unbranched alkyl; R.sup.C2 is either C.sub.1-3 unbranched alkyl or C.sub.3-4 branched alkyl; R.sup.C3 is selected from C.sub.1-3 unbranched alkyl and C.sub.2H.sub.4CO.sub.2H; R.sup.C4 is either H or Me; R.sup.C5 is either H or Me; R.sup.C6 represents one or two optional methyl substituents; and n is an integer from 2 to 8.

##STR00001##

Methods for treating Filoviridae virus infections

Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: ##STR00001##
The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

KILLING SENESCENT CELLS AND TREATING SENESCENCE-ASSOCIATED CONDITIONS USING A SRC INHIBITOR AND A FLAVONOID

Provided herein are methods and uses for treatment or prophylaxis of a senescent cell associated disease or disorder by administering a senolytic combination comprising dasatinib and quercetin or an analog thereof to a subject in need thereof. In certain embodiments, the senescent cell associated disease or disorder is a cardiovascular disease or disorder, inflammatory disease or disorder, a pulmonary disease or disorder, a neurological disease or disorder, or a metabolic disease or disorder.

KILLING SENESCENT CELLS AND TREATING SENESCENCE-ASSOCIATED CONDITIONS USING A SRC INHIBITOR AND A FLAVONOID

Provided herein are methods and uses for treatment or prophylaxis of a senescent cell associated disease or disorder by administering a senolytic combination comprising dasatinib and quercetin or an analog thereof to a subject in need thereof. In certain embodiments, the senescent cell associated disease or disorder is a cardiovascular disease or disorder, inflammatory disease or disorder, a pulmonary disease or disorder, a neurological disease or disorder, or a metabolic disease or disorder.

Combination Therapy Effective Against Microorganisms, Including Drug Resistant Microorganisms

Novel antimicrobial compositions comprise at least a form of a fosfomycin (or suitable analogs, or derivatives thereof), and at least one sulfonamide (or suitable analogs, or derivatives thereof), and/or at least one diaminopyridine (or suitable analogs, or derivatives thereof). Said antimicrobial compositions generally include two or more of said components as a novel combination, provided in a single combination or formulation, or provided independently with overlapping exposures of the two or more components. These novel compositions, when provided as the two or more components, are effective against susceptible microorganisms, and are effective against susceptible drug-resistant microorganisms (e.g., bacteria, parasites), including multi-drug resistant bacteria. These novel compositions are also effective against microorganisms or strains thereof now susceptible to the combination even though said microorganisms or strains thereof were previously found or were considered resistant or intolerant to at least one of the components of the novel composition, when the at least one component was used alone at what was considered an effective dosing amount or concentration.

Combination Therapy Effective Against Microorganisms, Including Drug Resistant Microorganisms

Novel antimicrobial compositions comprise at least a form of a fosfomycin (or suitable analogs, or derivatives thereof), and at least one sulfonamide (or suitable analogs, or derivatives thereof), and/or at least one diaminopyridine (or suitable analogs, or derivatives thereof). Said antimicrobial compositions generally include two or more of said components as a novel combination, provided in a single combination or formulation, or provided independently with overlapping exposures of the two or more components. These novel compositions, when provided as the two or more components, are effective against susceptible microorganisms, and are effective against susceptible drug-resistant microorganisms (e.g., bacteria, parasites), including multi-drug resistant bacteria. These novel compositions are also effective against microorganisms or strains thereof now susceptible to the combination even though said microorganisms or strains thereof were previously found or were considered resistant or intolerant to at least one of the components of the novel composition, when the at least one component was used alone at what was considered an effective dosing amount or concentration.

Combination Therapy Effective Against Microorganisms, Including Drug Resistant Microorganisms

Novel antimicrobial compositions comprise at least a form of a fosfomycin (or suitable analogs, or derivatives thereof), and at least one sulfonamide (or suitable analogs, or derivatives thereof), and/or at least one diaminopyridine (or suitable analogs, or derivatives thereof). Said antimicrobial compositions generally include two or more of said components as a novel combination, provided in a single combination or formulation, or provided independently with overlapping exposures of the two or more components. These novel compositions, when provided as the two or more components, are effective against susceptible microorganisms, and are effective against susceptible drug-resistant microorganisms (e.g., bacteria, parasites), including multi-drug resistant bacteria. These novel compositions are also effective against microorganisms or strains thereof now susceptible to the combination even though said microorganisms or strains thereof were previously found or were considered resistant or intolerant to at least one of the components of the novel composition, when the at least one component was used alone at what was considered an effective dosing amount or concentration.

Method of treating glycogen storage disease
11202789 · 2021-12-21 · ·

The present disclosure provides methods and compositions for the treatment of hepatic symptoms of glycogen storage diseases through the administration of thyroid hormone receptor agonists. The methods and compositions provided herein are useful in the treatment of hyperlipidemia, hypercholesterolemia, hepatic steatosis, cardiomegaly, hepatomegaly, hepatic fibrosis, and cirrhosis associated with glycogen storage diseases (GSD) and defects of glycogen metabolism. Said compounds may also be useful in the prevention of GSD-related hepatocellular adenoma and hepatocellular carcinoma.

Method of treating glycogen storage disease
11202789 · 2021-12-21 · ·

The present disclosure provides methods and compositions for the treatment of hepatic symptoms of glycogen storage diseases through the administration of thyroid hormone receptor agonists. The methods and compositions provided herein are useful in the treatment of hyperlipidemia, hypercholesterolemia, hepatic steatosis, cardiomegaly, hepatomegaly, hepatic fibrosis, and cirrhosis associated with glycogen storage diseases (GSD) and defects of glycogen metabolism. Said compounds may also be useful in the prevention of GSD-related hepatocellular adenoma and hepatocellular carcinoma.