Abstract

The present invention relates to the use of selective aquaporin inhibitors, e.g., of aquaporin-4 or aquaporin-2, e.g., certain phenylbenzamide compounds, for the prophylaxis, treatment and control of aquaporin-mediated conditions, e.g., diseases ofwater imbalance, for example edema (particularly edema of the brain and spinal cord, e.g., following trauma or ischemic stroke, as well as the edema associated with glioma, meningitis, acute mountain sickness, epileptic seizures, infections, metabolic disorders, hypoxia, water intoxication, hepatic failure, hepatic encephalopathy, diabetic ketoacidosis, abscess, eclampsia, Creutzfeldt-Jakob disease, and lupus cerebritis, as well as edema consequent to microgravity and/or radiation exposure, as well as edema consequent to invasive central nervous system procedures, e.g., neurosurgery, endovascular clot removal, spinal tap, aneurysm repair, or deep brain stimulation, as well as retinal edema), as well as hyponatremia and excess fluid retention, and diseases such as epilepsy, retinal ischemia and other diseases of the eye associated with abnormalities in intraocular pressure and/or tissue hydration, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines, as well as to novel assays for identifying aquaporin inhibitors.

IPC Classes  ?

• C07C 235/64 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho- position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• 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
• A61K 31/24 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine
• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• A61K 31/6615 - Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
• C07D 295/185 - Radicals derived from carboxylic acids from aliphatic carboxylic acids
• C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds

Abstract

Provided are novel formulations of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate as described below and uses thereof.

IPC Classes  ?

• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• A61K 9/00 - Medicinal preparations characterised by special physical form
• 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
• A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• C07F 9/09 - Esters of phosphoric acids

Abstract

Provided are crystals of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate, compositions comprising the same, and methods of making and using such crystals.

IPC Classes  ?

• C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds
• 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

Abstract

Provided are a pharmaceutical composition of an aquaporin inhibitor and a preparation method thereof. The pharmaceutical composition comprises 2-((3,5-bis (trifluoromethyl) phenyl)carbamoyl)-4-chlorophenyl dihydrogen phosphate or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and meglumine. The pharmaceutical composition of the aquaporin inhibitor and the preparation method thereof have the following advantages: the process is simple, has strong operability, and is conducive to industrial production, and the product has good stability, and obviously less content of degradable impurities, which ensures the effectiveness of the medicine.

IPC Classes  ?

• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• A61K 31/133 - Amines, e.g. amantadine having hydroxy groups, e.g. sphingosine
• A61K 9/19 - Particulate form, e.g. powders lyophilised
• A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• A61K 47/02 - Inorganic compounds
• A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
• A61K 9/00 - Medicinal preparations characterised by special physical form

Abstract

Provided are crystals of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate, compositions comprising the same, and methods of making and using such crystals.

IPC Classes  ?

• C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds
• 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

Abstract

Provided are novel prodrug salts of selective aquaporin inhibitors, their use as pharmaceuticals, and pharmaceutical compositions comprising them, and novel processes for their synthesis and novel intermediates for use in their synthesis. Also provided is use of a compound for the prophylaxis, treatment, and control of aquaporin-mediated conditions. Aquaporin inhibitors, e.g., inhibitors of AQP4 and/or AQP2, may be of utility in the treatment or control of diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord), hyponatremia, and excess fluid retention, as well as diseases such as epilepsy, retinal ischemia and other diseases of the eye, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines.

IPC Classes  ?

• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• A61K 9/00 - Medicinal preparations characterised by special physical form
• 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
• A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• C07F 9/09 - Esters of phosphoric acids

Abstract

The present invention relates to the use of selective aquaporin inhibitors, e.g., of aquaporin-4 or aquaporin-2, e.g., certain phenylbenzamide compounds, for the prophylaxis, treatment and control of aquaporin-mediated conditions, e.g., diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord, e.g., following trauma or ischemic stroke, as well as the edema associated with glioma, meningitis, acute mountain sickness, epileptic seizures, infections, metabolic disorders, hypoxia, water intoxication, hepatic failure, hepatic encephalopathy, diabetic ketoacidosis, abscess, eclampsia, Creutzfeldt-Jakob disease, and lupus cerebritis, as well as edema consequent to microgravity and/or radiation exposure, as well as edema consequent to invasive central nervous system procedures, e.g., neurosurgery, endovascular clot removal, spinal tap, aneurysm repair, or deep brain stimulation, as well as retinal edema), as well as hyponatremia and excess fluid retention, and diseases such as epilepsy, retinal ischemia and other diseases of the eye associated with abnormalities in intraocular pressure and/or tissue hydration, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines, as well as to novel assays for identifying aquaporin inhibitors.

IPC Classes  ?

• A61K 31/24 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• A61K 31/6615 - Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
• 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
• C07C 235/64 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho- position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• C07D 295/185 - Radicals derived from carboxylic acids from aliphatic carboxylic acids
• C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine

Abstract

Provided are a pharmaceutical composition of an aquaporin inhibitor and a preparation method thereof. The pharmaceutical composition comprises 2-((3,5-bis (trifluoromethyl) phenyl)carbamoyl)-4-chlorophenyl dihydrogen phosphate or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and meglumine. The pharmaceutical composition of the aquaporin inhibitor and the preparation method thereof have the following advantages: the process is simple, has strong operability, and is conducive to industrial production, and the product has good stability, and obviously less content of degradable impurities, which ensures the effectiveness of the medicine.

IPC Classes  ?

• 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
• A61K 31/24 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
• A61K 31/6615 - Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 25/14 - Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia

Abstract

Provided are a pharmaceutical composition of an aquaporin inhibitor and a preparation method thereof. The pharmaceutical composition comprises 2-((3,5-bis (trifluoromethyl) phenyl)carbamoyl)-4-chlorophenyl dihydrogen phosphate or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and meglumine. The pharmaceutical composition of the aquaporin inhibitor and the preparation method thereof have the following advantages: the process is simple, has strong operability, and is conducive to industrial production, and the product has good stability, and obviously less content of degradable impurities, which ensures the effectiveness of the medicine.

IPC Classes  ?

• 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
• A61K 31/6615 - Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
• A61K 31/24 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 25/14 - Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia

Abstract

Provided are novel formulations of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate as described below and uses thereof.

IPC Classes  ?

• 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
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine
• C07F 9/09 - Esters of phosphoric acids
• A61K 9/00 - Medicinal preparations characterised by special physical form

Abstract

Provided are novel prodrug salts of selective aquaporin inhibitors, their use as pharmaceuticals, and pharmaceutical compositions comprising them, and novel processes for their synthesis and novel intermediates for use in their synthesis. Also provided is use of a compound for the prophylaxis, treatment, and control of aquaporin-mediated conditions. Aquaporin inhibitors, e.g., inhibitors of AQP4 and/or AQP2, may be of utility in the treatment or control of diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord), hyponatremia, and excess fluid retention, as well as diseases such as epilepsy, retinal ischemia and other diseases of the eye, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines.

IPC Classes  ?

• 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
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine
• C07F 9/09 - Esters of phosphoric acids
• A61K 9/00 - Medicinal preparations characterised by special physical form

Abstract

Provided are novel formulations of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate as described below and uses thereof.

IPC Classes  ?

• 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
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine
• C07F 9/09 - Esters of phosphoric acids
• A61K 9/00 - Medicinal preparations characterised by special physical form

Abstract

Provided are crystals of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate, compositions comprising the same, and methods of making and using such crystals.

IPC Classes  ?

• C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds
• 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

Abstract

The present invention relates to the use of selective aquaporin inhibitors, e.g., of aquaporin-4 or aquaporin-2, e.g., certain phenylbenzamide compounds, for the prophylaxis, treatment and control of aquaporin-mediated conditions, e.g., diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord, e.g., following trauma or ischemic stroke, as well as the edema associated with glioma, meningitis, acute mountain sickness, epileptic seizures, infections, metabolic disorders, hypoxia, water intoxication, hepatic failure, hepatic encephalopathy, diabetic ketoacidosis, abscess, eclampsia, Creutzfeldt-Jakob disease, and lupus cerebritis, as well as edema consequent to microgravity and/or radiation exposure, as well as edema consequent to invasive central nervous system procedures, e.g., neurosurgery, endovascular clot removal, spinal tap, aneurysm repair, or deep brain stimulation, as well as retinal edema), as well as hyponatremia and excess fluid retention, and diseases such as epilepsy, retinal ischemia and other diseases of the eye associated with abnormalities in intraocular pressure and/or tissue hydration, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines, as well as to novel assays for identifying aquaporin inhibitors.

IPC Classes  ?

• C07C 235/64 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho- position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• A61K 31/24 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• A61K 31/6615 - Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine
• 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
• C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds
• C07D 295/185 - Radicals derived from carboxylic acids from aliphatic carboxylic acids

Abstract

Provided are novel prodrug salts of selective aquaporin inhibitors, their use as pharmaceuticals, and pharmaceutical compositions comprising them, and novel processes for their synthesis and novel intermediates for use in their synthesis. Also provided is use of a compound for the prophylaxis, treatment, and control of aquaporin-mediated conditions. Aquaporin inhibitors, e.g., inhibitors of AQP4 and/or AQP2, may be of utility in the treatment or control of diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord), hyponatremia, and excess fluid retention, as well as diseases such as epilepsy, retinal ischemia and other diseases of the eye, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines.

IPC Classes  ?

• C07F 9/09 - Esters of phosphoric acids
• 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
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine

Abstract

Provided are crystals of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate, compositions comprising the same, and methods of making and using such crystals.

IPC Classes  ?

• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds

Abstract

Provided are crystals of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate, compositions comprising the same, and methods of making and using such crystals.

IPC Classes  ?

• 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

Abstract

The present invention relates to the use of selective aquaporin inhibitors, e.g., of aquaporin-4 or aquaporin-2, e.g., certain phenylbenzamide compounds, for the prophylaxis, treatment and control of aquaporin-mediated conditions, e.g., glioblastoma and ovarian hyperstimulation syndrome. The invention provides, inter alia, methods of treating or controlling a disease condition mediated by an aquaporin, e.g., diseases or conditions of water imbalance and other diseases.

IPC Classes  ?

• 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
• C07F 9/09 - Esters of phosphoric acids
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine

Abstract

Provided are novel prodrug salts of selective aquaporin inhibitors, their use as pharmaceuticals, and pharmaceutical compositions comprising them, and novel processes for their synthesis and novel intermediates for use in their synthesis. Also provided is use of a compound for the prophylaxis, treatment, and control of aquaporin-mediated conditions. Aquaporin inhibitors, e.g., inhibitors of AQP4 and/or AQP2, may be of utility in the treatment or control of diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord), hyponatremia, and excess fluid retention, as well as diseases such as epilepsy, retinal ischemia and other diseases of the eye, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines.

IPC Classes  ?

• C07F 9/02 - Phosphorus compounds
• 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
• C07F 9/09 - Esters of phosphoric acids
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine

Abstract

Provided are uses of selective aquaporin inhibitors, e.g., of aquaporin-4 or aquaporin-2, e.g., certain phenylbenzamide compounds, for the treatment or prophylaxis of transplant rejection and the protection of the heart during heart surgery. Provided is the use of selective aquaporin inhibitors, e.g., of aquaporin-4 (AQP4) or aquaporin-2 (AQP2) for the treatment or prophylaxis of transplant rejection and for the protection of the heart during heart surgery.

IPC Classes  ?

• C07C 235/64 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho- position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring

Abstract

The present invention relates to the use of selective aquaporin inhibitors, e.g., of aquaporin-4 or aquaporin-2, e.g., certain phenylbenzamide compounds, for the prophylaxis, treatment and control of aquaporin-mediated conditions, e.g., diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord, e.g., following trauma or ischemic stroke, as well as the edema associated with glioma, meningitis, acute mountain sickness, epileptic seizures, infections, metabolic disorders, hypoxia, water intoxication, hepatic failure, hepatic encephalopathy, diabetic ketoacidosis, abscess, eclampsia, Creutzfeldt-Jakob disease, and lupus cerebritis, as well as edema consequent to microgravity and/or radiation exposure, as well as edema consequent to invasive central nervous system procedures, e.g., neurosurgery, endovascular clot removal, spinal tap, aneurysm repair, or deep brain stimulation, as well as retinal edema), as well as hyponatremia and excess fluid retention, and diseases such as epilepsy, retinal ischemia and other diseases of the eye associated with abnormalities in intraocular pressure and/or tissue hydration, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines, as well as to novel assays for identifying aquaporin inhibitors.

IPC Classes  ?

• C07C 235/64 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho- position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• 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
• A61K 31/24 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• A61K 31/6615 - Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine
• C07D 295/185 - Radicals derived from carboxylic acids from aliphatic carboxylic acids
• C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds

Abstract

Provided are novel formulations of 2-{ [3,5-bis( trifluoromethyl)phenyl ]carbamoyl} -4-chlorophenyl dihydrogen phosphate as described below and uses thereof. Also provided are kits comprising 2-{[3,5-bis(trifIuoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate. Also provided is a method of treating or controlling a disease or condition mediated by an aquaporin, e.g., diseases or conditions of water imbalance and other diseases.

IPC Classes  ?

• 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

Abstract

Provided are novel formulations of 2-{ [3,5-bis( trifluoromethyl)phenyl ]carbamoyl} -4-chlorophenyl dihydrogen phosphate as described below and uses thereof. Also provided are kits comprising 2-{[3,5-bis(trifIuoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate. Also provided is a method of treating or controlling a disease or condition mediated by an aquaporin, e.g., diseases or conditions of water imbalance and other diseases.

IPC Classes  ?

• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds

Abstract

The present invention relates to the use of selective aquaporin inhibitors, e.g., of aquaporin-4 or aquaporin-2, e.g., certain phenylbenzamide compounds, for the prophylaxis, treatment and control of aquaporin-mediated conditions, e.g., diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord, e.g., following trauma or ischemic stroke, as well as the edema associated with glioma, meningitis, acute mountain sickness, epileptic seizures, infections, metabolic disorders, hypoxia, water intoxication, hepatic failure, hepatic encephalopathy, diabetic ketoacidosis, abscess, eclampsia, Creutzfeldt-Jakob disease, and lupus cerebritis, as well as edema consequent to microgravity and/or radiation exposure, as well as edema consequent to invasive central nervous system procedures, e.g., neurosurgery, endovascular clot removal, spinal tap, aneurysm repair, or deep brain stimulation, as well as retinal edema), as well as hyponatremia and excess fluid retention, and diseases such as epilepsy, retinal ischemia and other diseases of the eye associated with abnormalities in intraocular pressure and/or tissue hydration, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines, as well as to novel assays for identifying aquaporin inhibitors.

IPC Classes  ?

• 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
• A61K 31/24 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• A61K 31/6615 - Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine
• C07C 235/64 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho- position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• C07D 295/185 - Radicals derived from carboxylic acids from aliphatic carboxylic acids
• C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds

Abstract

The present invention relates to the use of selective aquaporin inhibitors, e.g., of aquaporin-4 or aquaporin-2, e.g., certain phenylbenzamide compounds, for the prophylaxis, treatment and control of aquaporin-mediated conditions, e.g., glioblastoma and ovarian hyperstimulation syndrome. The invention provides, inter alia, methods of treating or controlling a disease condition mediated by an aquaporin, e.g., diseases or conditions of water imbalance and other diseases.

IPC Classes  ?

• 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

Abstract

Provided are novel prodrug salts of selective aquaporin inhibitors, their use as pharmaceuticals, and pharmaceutical compositions comprising them, and novel processes for their synthesis and novel intermediates for use in their synthesis. Also provided is use of a compound for the prophylaxis, treatment, and control of aquaporin-mediated conditions. Aquaporin inhibitors, e.g., inhibitors of AQP4 and/or AQP2, may be of utility in the treatment or control of diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord), hyponatremia, and excess fluid retention, as well as diseases such as epilepsy, retinal ischemia and other diseases of the eye, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines.

IPC Classes  ?

• 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

Abstract

The present invention relates to the use of selective aquaporin inhibitors, e.g., of aquaporin-4 or aquaporin-2, e.g., certain phenylbenzamide compounds, for the prophylaxis, treatment and control of aquaporin-mediated conditions, e.g., diseases of water imbalance, for example edema, as well as hyponatremia and excess fluid retention, and diseases such as epilepsy, retinal ischemia and other diseases of the eye associated with abnormalities in intraocular pressure and/or tissue hydration, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines, as well as to novel assays for identifying aquaporin inhibitors.

IPC Classes  ?

• 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
• A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds