The present invention provides novel liver-targeted prodrugs of mitochondrial proton ionophores. These compounds have utility in medicine including their use in treatment of diseases such as NASH and NAFLD.
A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
3.
PROTECTED CARBOXYLIC ACID-BASED METABOLITES FOR THE TREATMENT OF MITOCHONDRIA-RELATED DISEASES
The present invention provides novel cell-permeable carboxylic acid-based metabolites and cell permeable precursors thereof aimed at increasing ATP-production in mitochondria and thus, for use in medicine. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane, one of them being malonate. The provision of the novel cell permeable carboxylic acid- based metabolites is envisaged to allow passage over the cellular membrane and thus the cell permeable metabolite can be used to enhance mitochondrial ATP-output.
C07C 235/80 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms having carbon atoms of carboxamide groups and keto groups bound to the same carbon atom, e.g. acetoacetamides
The present invention provides novel cell-permeable fumarate acyl mercaptoethylamines (FAMs) which have cellular effects including induction of Nrf2 and inhibition of the NFkB pathway. These compounds have utility in medicine including their use in treatment of diseases such as Multiple sclerosis, Non-alcoholic Steatohepatitis, Psoriasis, Inflammatory Arthritis, Inflammatory Bowel Disease, Asthma, Chronic Obstructive Pulmonary Disease, Cancer, Parkinson's Disease, Alzheimer's Disease, Huntington's Disease and Amyotrophic Lateral Sclerosis.
C07C 327/06 - Monothiocarboxylic acids having carbon atoms of thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of an acyclic saturated carbon skeleton
C07C 327/34 - Esters of monothiocarboxylic acids having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by carboxyl groups with amino groups bound to the same hydrocarbon radicals
C07D 211/76 - Oxygen atoms attached in position 2 or 6
C07C 327/08 - Monothiocarboxylic acids having carbon atoms of thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a saturated carbon skeleton containing rings
The present invention provides novel cell-permeable carboxylic acid-based metabolites and cell permeable precursors thereof aimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane, one of them being malonate. The provision of the novel cell permeable carboxylic acid-based metabolites is envisaged to allow passage over the cellular membrane and thus the cell permeable metabolite can be used to enhance mitochondrial ATP-output.
C07D 207/452 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom
C07C 327/06 - Monothiocarboxylic acids having carbon atoms of thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of an acyclic saturated carbon skeleton
C07D 209/48 - Iso-indolesHydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
The present invention provides novel cell-permeable carboxylic acid- based metabolites and cell permeable precursors thereof aimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high- energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane. The provision of the novel cell permeable carboxylic acid-based metabolites is envisaged to allow passage over the cellular membrane and thus the cell permeable carboxylic acid-based metabolites can be used to enhance mitochondrial ATP-output.
C07C 327/06 - Monothiocarboxylic acids having carbon atoms of thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of an acyclic saturated carbon skeleton
C07C 327/34 - Esters of monothiocarboxylic acids having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by carboxyl groups with amino groups bound to the same hydrocarbon radicals
C07C 327/08 - Monothiocarboxylic acids having carbon atoms of thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a saturated carbon skeleton containing rings
The present invention provides novel cell-permeable succinates and cell permeable precursors of succinate aimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane, one of them being succinate. The provision of the novel cell permeable succinates is envisaged to allow passage over the cellular membrane and thus the cell permeable succinates can be used to enhance mitochondrial ATP-output.
C07D 323/00 - Heterocyclic compounds containing more than two oxygen atoms as the only ring hetero atoms
C07D 273/02 - Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups having two nitrogen atoms and only one oxygen atom
The present invention provides novel cell-permeable succinates and cell permeable precursors of succinate aimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane, one of them being succinate. The provision of the novel cell permeable succinates is envisaged to allow passage over the cellular membrane and thus the cell permeable succinates can be used to enhance mitochondrial ATP-output.
C07C 323/25 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
9.
SUCCINATE PRODRUGS FOR USE IN THE TREATMENT OF LACTIC ACIDOSIS OR DRUG-INDUCED SIDE-EFFECTS DUE TO COMPLEX I-RELATED IMPAIRMENT OF MITOCHONDRIAL OXIDATIVE PHOSPHORYLATION
A novel method useful in drug screening. The method is useful for testing effects of substances on the mitochondria, notably toxic or beneficial effects of drug substances or candidate drug substances. The method is based on measurement in live human mitochondria ex vivo, but in a setting as near the in vivo situation as possible. The method is also useful for testing substances impact on the mitochondrial respiration. The method can be used to i) screening and selection of early or late stage drug candidates in cells derived from blood from healthy individuals or in so-called buffy coat, which is a concentrated solution of platelets and white blood cells, ii) testing a patient's sensitivity to a known mitochondrial toxicant, iii) analysing mitochondrial drug toxicity in clinical trials, and/or iv) analysing beneficial effects of drugs intended to improve mitochondrial function
There is provided inter alia apharmaceutical dosage form fororal administration comprising a sanglifehrin as active ingredient in which the sanglifehrin active ingredient is protected from acid degradation in the stomach environment following oral administration.
The present invention relates to a cyclosporine emulsion containing: i) a cyclosporine ii) a natural oil (long chain triglyceride) iii) a phosphatidylcholine, iv) glycerol, v) a pharmaceutically tolerable alkali salt of a free fatty acid, vi) a medium chain triglyceride-oil vii) optionally, hydrochloric acid or sodium hydroxide for pH adjustment viii) water.
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