RU2011110435A - Пролекарства метилгидрофумарата, фармацетические композиции с ними и способы применения - Google Patents

Пролекарства метилгидрофумарата, фармацетические композиции с ними и способы применения Download PDF

Info

Publication number
RU2011110435A
RU2011110435A RU2011110435/04A RU2011110435A RU2011110435A RU 2011110435 A RU2011110435 A RU 2011110435A RU 2011110435/04 A RU2011110435/04 A RU 2011110435/04A RU 2011110435 A RU2011110435 A RU 2011110435A RU 2011110435 A RU2011110435 A RU 2011110435A
Authority
RU
Russia
Prior art keywords
methyl
dioate
alkyl
substituted
ethyl
Prior art date
Application number
RU2011110435/04A
Other languages
English (en)
Other versions
RU2554347C2 (ru
Inventor
Арчана ГАНГАКХЕДКАР (US)
Арчана ГАНГАКХЕДКАР
Сюэдонг ДАИ (US)
Сюэдонг ДАИ
Ноа ЗЕРАНГ (US)
Ноа ЗЕРАНГ
Питер А. ВИРСИК (US)
Питер А. ВИРСИК
Original Assignee
Ксенопорт, Инк. (Us)
Ксенопорт, Инк.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ксенопорт, Инк. (Us), Ксенопорт, Инк. filed Critical Ксенопорт, Инк. (Us)
Publication of RU2011110435A publication Critical patent/RU2011110435A/ru
Application granted granted Critical
Publication of RU2554347C2 publication Critical patent/RU2554347C2/ru

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/08—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/10—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/12—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
    • C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
    • C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/62—Compounds containing any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylcarbamates
    • C07C271/64—Y being a hydrogen or a carbon atom, e.g. benzoylcarbamates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/46—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylureas
    • C07C275/48—Y being a hydrogen or a carbon atom
    • C07C275/50—Y being a hydrogen or an acyclic carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/52—Esters of acyclic unsaturated carboxylic acids having the esterified carboxyl group bound to an acyclic carbon atom
    • C07C69/593—Dicarboxylic acid esters having only one carbon-to-carbon double bond
    • C07C69/60—Maleic acid esters; Fumaric acid esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C69/75—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring of acids with a six-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/78—Benzoic acid esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/96—Esters of carbonic or haloformic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—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
    • C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—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 no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Cardiology (AREA)
  • Dermatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Vascular Medicine (AREA)
  • Psychiatry (AREA)
  • Psychology (AREA)
  • Urology & Nephrology (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Pyrrole Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

1. Соединение формулы (I) !! или его фармацевтически приемлемая соль, где в указанной формуле ! R1 и R2 выбирают независимо из водорода, C1-6-алкила и замещенного C1-6-алкила; ! R3 и R4 выбирают независимо из водорода, C1-6-алкила, замещенного C1-6-алкила, C1-6-гетероалкила, замещенного C1-6-гетероалкила, С4-12-циклоалкилалкила, замещенного С4-12-циклоалкилалкила, С7-12-арилалкила и замещенного С7-12-арилалкила; или R3 и R4 вместе с атомом азота, с которым они связаны, образуют цикл, выбранный из C5-10-гетероарила, замещенного С5-10-гетероарила, С5-10-гетероциклоалкила и замещенного C5-10-гетероциклоалкила; и ! R5 выбирают из метила, этила и С3-6-алкила; ! где каждую группу-заместитель выбирают независимо из галогена, -ОН, -CN, -CF3, =O, -NO2, бензила, -C(O)NR11 2, -R11, -OR11, -C(O)R11, -COOR11 и -NR11 2, где каждый R11 выбирают независимо из водорода и С1-4-алкила; ! при условии, что когда R5 представляет собой этил, тогда R3 и R4 выбирают независимо из водорода, C1-6-алкила и замещенного C1-6-алкила. ! 2. Соединение по п.1, где каждый из R1 и R2 представляет собой водород. ! 3. Соединение по п.1, где один из R1 и R2 представляет собой водород, и другой из R1 и R2 выбирают из метила, этила, н-пропила, изопропила, н-бутила, изобутила и вторбутила. ! 4. Соединение по п.1, где R3 и R4 выбирают независимо из водорода и C1-6-алкила. ! 5. Соединение по п.1, где R3 и R4 вместе с атомом азота, с которым они связаны, образуют С5-10-гетероциклоалкил. ! 6. Соединение по п.1, где один из R1 и R2 представляет собой водород, и другой из R1 и R2 выбирают из водорода и C1-6-алкила; и R3 и R4 вместе с атомом азота, с которым они связаны, образуют цикл, выбранный из морфолина, пиперазина и N-замещенного пиперазина. ! 7. Соединение по п.1, где R5 представляет собой метил. !

Claims (25)

1. Соединение формулы (I)
Figure 00000001
или его фармацевтически приемлемая соль, где в указанной формуле
R1 и R2 выбирают независимо из водорода, C1-6-алкила и замещенного C1-6-алкила;
R3 и R4 выбирают независимо из водорода, C1-6-алкила, замещенного C1-6-алкила, C1-6-гетероалкила, замещенного C1-6-гетероалкила, С4-12-циклоалкилалкила, замещенного С4-12-циклоалкилалкила, С7-12-арилалкила и замещенного С7-12-арилалкила; или R3 и R4 вместе с атомом азота, с которым они связаны, образуют цикл, выбранный из C5-10-гетероарила, замещенного С5-10-гетероарила, С5-10-гетероциклоалкила и замещенного C5-10-гетероциклоалкила; и
R5 выбирают из метила, этила и С3-6-алкила;
где каждую группу-заместитель выбирают независимо из галогена, -ОН, -CN, -CF3, =O, -NO2, бензила, -C(O)NR11 2, -R11, -OR11, -C(O)R11, -COOR11 и -NR11 2, где каждый R11 выбирают независимо из водорода и С1-4-алкила;
при условии, что когда R5 представляет собой этил, тогда R3 и R4 выбирают независимо из водорода, C1-6-алкила и замещенного C1-6-алкила.
2. Соединение по п.1, где каждый из R1 и R2 представляет собой водород.
3. Соединение по п.1, где один из R1 и R2 представляет собой водород, и другой из R1 и R2 выбирают из метила, этила, н-пропила, изопропила, н-бутила, изобутила и вторбутила.
4. Соединение по п.1, где R3 и R4 выбирают независимо из водорода и C1-6-алкила.
5. Соединение по п.1, где R3 и R4 вместе с атомом азота, с которым они связаны, образуют С5-10-гетероциклоалкил.
6. Соединение по п.1, где один из R1 и R2 представляет собой водород, и другой из R1 и R2 выбирают из водорода и C1-6-алкила; и R3 и R4 вместе с атомом азота, с которым они связаны, образуют цикл, выбранный из морфолина, пиперазина и N-замещенного пиперазина.
7. Соединение по п.1, где R5 представляет собой метил.
8. Соединение по п.1, где один из R1 и R2 представляет собой водород, и другой из R1 и R2 выбирают из водорода и C1-6-алкила; R3 представляет собой водород; R4 выбирают из водорода, C1-6-алкила и бензила; и R5 представляет собой метил.
9. Соединение по п.1, выбранное из группы, в которую входят
(N,N-диэтилкарбамоил)метил-метил(2Е)бут-2-ен-1,4-диоат;
метил-[N-бензилкарбамоил]метил(2Е)бут-2-ен-1,4-диоат;
метил-2-морфолин-4-ил-2-оксоэтил(2Е)бут-2-ен-1,4-диоат;
(N-бутилкарбамоил)метил-метил(2Е)бут-2-ен-1,4-диоат;
[N-(2-метоксиэтил)карбамоил]метил-метил(2Е)бут-2-ен-1,4-диоат;
2-{2-[(2Е)-3-(метоксикарбонил)проп-2-еноилокси]ацетиламино}уксусная кислота;
4-{2-[(2Е)-3-(метоксикарбонил)проп-2-еноилокси]ацетиламино}бутановая кислота;
метил-(N-(1,3,4-тиадиазол-2-ил)карбамоил)метил(2Е)бут-2-ен-1,4-диоат;
(N,N-диметилкарбамоил)метил-метил(2Е)бут-2-ен-1,4-диоат;
(N-метокси-N-метилкарбамоил)метил-метил(2Е)бут-2-ен-1,4-диоат;
бис(2-метоксиэтиламино)карбамоил]метил-метил(2Е)бут-2-ен-1,4-диоат;
[N-(метоксикарбонил)карбамоил]метил-метил(2Е)бут-2-ен-1,4-диоат;
4-{2-[(2Е)-3-(метоксикарбонил)проп-2-еноилокси]ацетиламино}бутановой кислоты, натриевая соль;
метил-2-оксо-2-пиперазинилэтил(2Е)бут-2-ен-1,4-диоат;
метил-2-оксо-2-(2-оксо(1,3-оксазолидин-3-ил)этил(2Е)бут-2-ен-1,4-диоат;
{N-[2-(диметиламино)этил]карбамоил}метил-метил(2Е)бут-2-ен-1,4-диоат;
метил-2-(4-метилпиперазинил)-2-оксоэтил(2Е)бут-2-ен-1,4-диоат;
метил-{N-[(пропиламино)карбонил]карбамоил}метил(2Е)бут-2-ен-1,4-диоат;
2-(4-ацетилпиперазинил)-2-оксоэтил-метил(2Е)бут-2-ен-1,4-диоат;
{N,N-бис[2-(метилэтокси)этил]карбамоил} метил-метил(2Е)бут-2-ен-1,4-диоат;
метил-2-(4-бензилпиперазинил)-2-оксоэтил(2Е)бут-2-ен-1,4-диоат;
[N,N-бис(2-этоксиэтил)карбамоил]метил-метил(2Е)бут-2-ен-1,4-диоат;
2-{(2S)-2-[(трет-бутил)оксикарбонил]пирролидинил}-2-оксоэтил-метил(2Е)бут-2-ен-1,4-диоат;
1-{2-[(2Е)-3-(метоксикарбонил)проп-2-еноилокси]ацетил}-(2S)-пирролидин-2-карбоновая кислота;
(N-{[(трет-бутил)оксикарбонил]метил}-N-метилкарбамоил)метил-метил(2Е)бут-2-ен-1,4-диоат;
{N-[(этоксикарбонил)метил]-N-метилкарбамоил}метил-метил(2Е)бут-2-ен-1,4-диоат;
метил-1-метил-2-морфолин-4-ил-2-оксоэтил(2Е)бут-2-ен-1,4-диоат;
[N,N-бис(2-метоксиэтил)карбамоил]этил-метил(2Е)бут-2-ен-1,4-диоат;
(N,N-диметилкарбамоил)этил-метил(2Е)бут-2-ен-1,4-диоат;
2-{2-[(2Е)-3-(метоксикарбонил)проп-2-еноилокси]-N-метилацетиламино}уксусная кислота;
(N-{[(третбутил)оксикарбонил]метил}карбамоил)метил-метил(2Е)бут-2-ен-1,4-диоат;
метил-(N-метил-N-{[(метилэтил)оксикарбонил]метил}карбамоил)метил(2Е)бут-2-ен-1,4-диоат;
{N-[(этоксикарбонил)метил]-N-бензилкарбамоил}метил-метил(2Е)бут-2-ен-1,4-диоат;
{N-[(этоксикарбонил)метил]-N-бензилкарбамоил}этил-метил(2Е)бут-2-ен-1,4-диоат;
{N-[(этоксикарбонил)метил]-N-метилкарбамоил}этил-метил(2Е)бут-2-ен-1,4-диоат;
(1S)-1-метил-2-морфолин-4-ил-2-оксоэтил-метил(2Е)бут-2-ен-1,4-диоат;
(1S)-1-[N,N-бис(2-метоксиэтил)карбамоил]этил-метил(2Е)бут-2-ен-1,4-диоат;
(1R)-1-(N,N-диэтилкарбамоил)этил-метил(2Е)бут-2-ен-1,4-диоат;
(N-[(метоксикарбонил)этил]карбамоил)метил-метил(2Е)бут-2-ен-1,4-диоат;
2-{2-[(2Е)-3-(метоксикарбонил)проп-2-еноилокси]ацетиламино}пропановая кислота и
фармацевтически приемлемая соль любого из вышеуказанных соединений.
10. Соединение формулы (II)
Figure 00000002
или его фармацевтически приемлемая соль, где в указанной формуле
R6 выбирают из C1-6-алкила, замещенного C1-6-алкила, C1-6-гетероалкила, замещенного C1-6-гетероалкила, С3-8-циклоалкила, замещенного С3-8-циклоалкила, С6-8-арила, замещенного С6-8-арила и -OR10, где R10 выбирают из C1-6-алкила, замещенного C1-6-алкила, С3-10-циклоалкила, замещенного С3-10-циклоалкила, С6-10-арила и замещенного С6-10-арила; R7 и R8 выбирают независимо из водорода, C1-6-алкила и замещенного C1-6-алкила; и
R9 выбирают из C1-6-алкила и замещенного C1-6-алкила;
где каждую группу-заместитель выбирают независимо из галогена, -ОН, -CN, -CF3, =O, -NO2, бензила, -C(O)NR11 2, -R11, -OR11, -C(O)R11, -COOR11 и -NR11 2, где каждый R11 выбирают независимо из водорода и C1-4-алкила.
11. Соединение по п.10, где один из R7 и R8 представляет собой водород, и другой из R7 и R8 выбирают из метила, этила, н-пропила и изопропила.
12. Соединение по п.10, где R9 выбирают из замещенного C1-6-алкила, и каждая группа-заместитель представляет собой -OR11, где каждый R11 представляет собой С1-4-алкил.
13. Соединение по п.10, где R9 выбирают из метила и этила.
14. Соединение по п.10, где R6 представляет собой C1-6-алкил; один из R7 и R8 представляет собой водород, и другой из R7 и R8 представляет собой C1-6-алкил; и R9 выбирают из C1-6-алкила и замещенного C1-6-алкила.
15. Соединение по п.10, где R6 представляет собой -OR10, где R10 выбирают из C1-4-алкила, циклогексила и фенила.
16. Соединение по п.10, где R6 выбирают из метила, этила, н-пропила и изопропила; и один из R7 и R8 представляет собой водород, и другой из R7 и R8 выбирают из метила, этила, н-пропила и изопропила.
17. Соединение по п.10, выбранное из группы, в которую входят
этоксикарбонилоксиэтил-метил(2Е)бут-2-ен-1,4-диоат;
метил-(метилэтоксикарбонилокси)этил(2Е)бут-2-ен-1,4-диоат;
метил-(2-метилпропаноилокси)этил(2Е)бут-2-ен-1,4-диоат;
метил-фенилкарбонилоксиэтил(2Е)бут-2-ен-1,4-диоат;
циклогексилоксикарбонилоксибутил-метил(2Е)бут-2-ен-1,4-диоат;
[(2Е)-3-(метоксикарбонил)проп-2-еноилокси]этил-метил(2Е)бут-2-ен-1,4-диоат;
(циклогексилоксикарбонилокси)этил-метил(2Е)бут-2-ен-1,4-диоат;
метил-2-метил-1-фенилкарбонилоксипропил(2Е)бут-2-ен-1,4-диоат; и
3-({[(2Е)-3-(метоксикарбонил)проп-2-еноилокси]метил}оксикарбонил)(3S)-3-аминопропановой кислоты, 2,2,2-трифторацетат;
3-({[(2Е)-3-(метоксикарбонил)проп-2-еноилокси]метил}оксикарбонил)(2S)-2-аминопропановой кислоты, 2,2,2-трифторацетат;
3-({[(2Е)-3-(метоксикарбонил)проп-2-еноилокси]метил}оксикарбонил)(3S)-3-(2-аминоацетиламино)пропановой кислоты, 2,2,2-трифторацетат;
3-{[(2Е)-3-(метоксикарбонил)проп-2-еноилокси]этоксикарбонилокси}(2S)-2-аминопропановой кислоты, хлорид; и
фармацевтически приемлемая соль любого из вышеуказанных соединений.
18. Фармацевтическая композиция, включающая соединение по п.1 и, по меньшей мере, один фармацевтически приемлемый носитель.
19. Фармацевтическая композиция по п.18, представляющая собой пероральный препарат.
20. Фармацевтическая композиция по п.18, в которой соединение присутствует в количестве, которое является эффективным для лечения заболевания, выбранного из псориаза, рассеянного склероза, воспалительного заболевания кишечника, астмы, хронической обструктивной болезни легких и артрита.
21. Способ лечения заболевания у пациента, включающий введение пациенту, нуждающемуся в таком лечении, терапевтически эффективного количества фармацевтической композиции по п.18, где заболевание выбирают из псориаза, рассеянного склероза, воспалительного заболевания кишечника, астмы, хронической обструктивной болезни легких и артрита.
22. Фармацевтическая композиция, включающая соединение по п.10 и, по меньшей мере, один фармацевтически приемлемый носитель.
23. Фармацевтическая композиция по п.22, представляющая собой пероральный препарат.
24. Фармацевтическая композиция по п.22, в которой соединение присутствует в количестве, которое является эффективным для лечения заболевания, выбранного из псориаза, рассеянного склероза, воспалительного заболевания кишечника, астмы, хронической обструктивной болезни легких и артрита.
25. Способ лечения заболевания у пациента, включающий введение пациенту, нуждающемуся в таком лечении, терапевтически эффективного количества фармацевтической композиции по п.22, где заболевание выбирают из псориаза, рассеянного склероза, воспалительного заболевания кишечника, астмы, хронической обструктивной болезни легких и артрита.
RU2011110435/04A 2008-08-19 2009-08-19 Пролекарства метилгидрофумарата, фармацевтические композиции с ними и способы применения RU2554347C2 (ru)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US9016308P 2008-08-19 2008-08-19
US61/090,163 2008-08-19
PCT/US2009/054349 WO2010022177A2 (en) 2008-08-19 2009-08-19 Prodrugs of methyl hydrogen fumarate, pharmaceutical compositions thereof, and methods of use

Publications (2)

Publication Number Publication Date
RU2011110435A true RU2011110435A (ru) 2012-09-27
RU2554347C2 RU2554347C2 (ru) 2015-06-27

Family

ID=41572470

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2011110435/04A RU2554347C2 (ru) 2008-08-19 2009-08-19 Пролекарства метилгидрофумарата, фармацевтические композиции с ними и способы применения

Country Status (20)

Country Link
US (4) US8148414B2 (ru)
EP (2) EP2334378B1 (ru)
JP (1) JP5670331B2 (ru)
CN (1) CN102123763B (ru)
AU (1) AU2009282888C1 (ru)
CA (2) CA2806444C (ru)
CY (1) CY1115203T1 (ru)
DK (1) DK2334378T3 (ru)
ES (1) ES2477884T3 (ru)
HK (1) HK1158563A1 (ru)
HR (1) HRP20140640T1 (ru)
IL (2) IL210579A (ru)
MX (1) MX2011001341A (ru)
NZ (3) NZ608196A (ru)
PL (1) PL2334378T3 (ru)
PT (1) PT2334378E (ru)
RU (1) RU2554347C2 (ru)
SI (1) SI2334378T1 (ru)
WO (1) WO2010022177A2 (ru)
ZA (1) ZA201100599B (ru)

Families Citing this family (119)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1663197B1 (en) 2003-09-09 2007-12-05 Fumapharm AG The use of fumaric acid derivatives for treating cardiac insufficiency, and asthma
LT2801354T (lt) * 2004-10-08 2017-06-26 Forward Pharma A/S Kontroliuojamo atpalaidavimo farmacinės kompozicijos, apimančios fumaro rūgšties esterį
HUE032251T2 (en) * 2007-02-08 2017-09-28 Biogen Ma Inc Neuroprotection in demyelinating diseases
MX2011001341A (es) 2008-08-19 2011-03-29 Xenoport Inc Prodrogas de metil hidrogeno fumarato, sus composiciones farmaceuticas, y metodos de uso.
US8906420B2 (en) 2009-01-09 2014-12-09 Forward Pharma A/S Pharmaceutical formulation comprising one or more fumaric acid esters in an erosion matrix
SG195049A1 (en) * 2011-05-26 2013-12-30 Biogen Idec Inc Methods of treating multiple sclerosis and preserving and/or increasing myelin content
WO2014037832A2 (en) 2012-09-06 2014-03-13 Mahesh Kandula Compositions and methods for the treatment of epilepsy and neurological diseases
US9504679B2 (en) 2011-12-19 2016-11-29 Bjoern Colin Kahrs Pharmaceutical compositions comprising glitazones and Nrf2 activators
US20130158077A1 (en) 2011-12-19 2013-06-20 Ares Trading S.A. Pharmaceutical compositions
JP5918395B2 (ja) * 2012-02-07 2016-05-18 ゼノポート，インコーポレイティド モルホリノアルキルフマレート化合物、医薬組成物及び使用方法
CN104220061A (zh) * 2012-02-07 2014-12-17 比奥根艾迪克依蒙菲利亚公司 含有富马酸二甲酯的药物组合物
CA2872975A1 (en) 2012-05-07 2013-11-14 Cellixbio Private Limited Compositions and methods for the treatment of neurological disorders
US9399634B2 (en) 2012-05-07 2016-07-26 Cellix Bio Private Limited Compositions and methods for the treatment of depression
AU2013257742A1 (en) 2012-05-07 2014-11-27 Cellixbio Private Limited Compositions and methods for treatment of neuromuscular disorders and neurodegenerative disorders
US9266823B2 (en) 2012-05-08 2016-02-23 Cellix Bio Private Limited Compositions and methods for the treatment of parkinson's disease
WO2013167992A1 (en) 2012-05-08 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of inflammatory disorders
WO2013168025A1 (en) 2012-05-08 2013-11-14 Mahesh Kandula Compositions and methods for treatment of blood clotting disorders
US9434704B2 (en) 2012-05-08 2016-09-06 Cellix Bio Private Limited Compositions and methods for the treatment of neurological degenerative disorders
WO2013167991A1 (en) 2012-05-08 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of metabolic disorders
SG11201407318UA (en) 2012-05-10 2014-12-30 Cellix Bio Private Ltd Compositions and methods for the treatment of metabolic syndrome
WO2013168004A2 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of fibromyalgia pain
WO2013168002A1 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of neurological conditions
WO2013168001A1 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of moderate to severe pain
WO2013168011A1 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of chronic pain
US9499527B2 (en) 2012-05-10 2016-11-22 Cellix Bio Private Limited Compositions and methods for the treatment of familial amyloid polyneuropathy
US9573927B2 (en) 2012-05-10 2017-02-21 Cellix Bio Private Limited Compositions and methods for the treatment of severe pain
WO2013167999A2 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of neurologic diseases
US9242939B2 (en) 2012-05-10 2016-01-26 Cellix Bio Private Limited Compositions and methods for the treatment of respiratory disorders
US9339484B2 (en) 2012-05-10 2016-05-17 Cellix Bio Private Limited Compositions and methods for the treatment of restless leg syndrome and fibromyalgia
US9394288B2 (en) 2012-05-10 2016-07-19 Cellix Bio Private Limited Compositions and methods for the treatment of asthma and allergy
WO2013168033A1 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for treatment of neurologic diseases
US9315478B2 (en) 2012-05-10 2016-04-19 Cellix Bio Private Limited Compositions and methods for the treatment of metabolic syndrome
US9227974B2 (en) 2012-05-23 2016-01-05 Cellex Bio Private Limited Compositions and methods for the treatment of respiratory disorders
US9434729B2 (en) 2012-05-23 2016-09-06 Cellix Bio Private Limited Compositions and methods for the treatment of periodontitis and rheumatoid arthritis
JP2015518855A (ja) 2012-05-23 2015-07-06 セリックスビオ プライヴェート リミテッド 粘膜炎の治療のための組成物および方法
SG11201407322QA (en) 2012-05-23 2014-12-30 Cellix Bio Private Ltd Compositions and methods for the treatment of multiple sclerosis
US9492409B2 (en) 2012-05-23 2016-11-15 Cellix Bio Private Limited Compositions and methods for the treatment of local pain
CA2873096A1 (en) 2012-05-23 2013-11-28 Cellixbio Private Limited Compositions and methods for the treatment of inflammatory bowel disease
JP2015519371A (ja) * 2012-05-30 2015-07-09 ゼノポート，インコーポレイティド フマル酸水素メチルのプロドラッグを用いた多発性硬化症及び乾癬の治療
US9108942B1 (en) 2014-11-05 2015-08-18 Mahesh Kandula Compositions and methods for the treatment of moderate to severe pain
US9187427B2 (en) 2012-08-03 2015-11-17 Cellix Bio Private Limited N-substituted nicotinamide compounds and compositions for the treatment migraine and neurologic diseases
US20200000758A1 (en) * 2012-08-22 2020-01-02 Xenoport, Inc. Oral Dosage Forms Of Methyl Hydrogen Fumarate And Prodrugs Thereof
JP2015526476A (ja) * 2012-08-22 2015-09-10 ゼノポート，インコーポレイティド メチル水素フマレートの経口剤形およびそのプロドラッグ
US10945984B2 (en) 2012-08-22 2021-03-16 Arbor Pharmaceuticals, Llc Methods of administering monomethyl fumarate and prodrugs thereof having reduced side effects
US20140057918A1 (en) * 2012-08-22 2014-02-27 Xenoport, Inc. Methods of Use for Monomethyl Fumarate and Prodrugs Thereof
US9624168B2 (en) 2012-09-06 2017-04-18 Cellix Bio Private Limited Compositions and methods for the treatment inflammation and lipid disorders
SG11201407325YA (en) 2012-09-08 2014-12-30 Cellix Bio Private Ltd Compositions and methods for treatment of inflammation and lipid disorders
WO2014071371A1 (en) 2012-11-05 2014-05-08 Xenoport, Inc. Cocrystals of (n,n-diethylcarbamoyl)methyl methyl (2e)but-2-ene-1,4-dioate
EP2742855A1 (en) * 2012-12-11 2014-06-18 Friedrich-Alexander-Universität Erlangen-Nürnberg Brain functional magnetic resonance activity is associated with response to tumor necrosis factor inhibition
US20140171504A1 (en) 2012-12-14 2014-06-19 Georgia Regents Research Institute, Inc. Methods of Treating Sickle Cell Disease and Related Disorders Using Fumaric Acid Esters
EP2934507B1 (en) * 2012-12-21 2017-05-31 ratiopharm GmbH Prodrugs of monomethyl fumarate (mmf)
AR094277A1 (es) * 2012-12-21 2015-07-22 Biogen Idec Inc Derivados de fumarato sustituidos con deuterio
US8669281B1 (en) 2013-03-14 2014-03-11 Alkermes Pharma Ireland Limited Prodrugs of fumarates and their use in treating various diseases
PT2970101T (pt) 2013-03-14 2018-10-04 Alkermes Pharma Ireland Ltd Pró-fármacos de fumaratos e seu uso no tratamento de várias doenças
WO2014143146A1 (en) * 2013-03-15 2014-09-18 Xenoport, Inc. Methods of administering monomethyl fumarate
US10179118B2 (en) 2013-03-24 2019-01-15 Arbor Pharmaceuticals, Llc Pharmaceutical compositions of dimethyl fumarate
US9333187B1 (en) 2013-05-15 2016-05-10 Cellix Bio Private Limited Compositions and methods for the treatment of inflammatory bowel disease
CA2914461A1 (en) 2013-06-04 2014-12-11 Cellixbio Private Limited Compositions and methods for the treatment of diabetes and pre-diabetes
WO2014197860A1 (en) 2013-06-07 2014-12-11 Xenoport, Inc. Method of making monomethyl fumarate
US9421182B2 (en) 2013-06-21 2016-08-23 Xenoport, Inc. Cocrystals of dimethyl fumarate
CA2919381A1 (en) * 2013-08-01 2015-02-05 Xenoport, Inc. Methods of administering monomethyl fumarate and prodrugs thereof having reduced side effects
WO2015017798A2 (en) * 2013-08-02 2015-02-05 CRIXlabs, Inc. Method and system for predicting spatial and temporal distributions of therapeutic substance carriers
JP2016534133A (ja) 2013-09-06 2016-11-04 ゼノポート，インコーポレイティド （ｎ，ｎ−ジエチルカルバモイル）メチル メチル（２ｅ）ブト−２−エン−１，４−ジオエートの結晶形態、その合成方法及び使用
US20160214948A1 (en) * 2013-09-27 2016-07-28 Ratiopharm Gmbh Prodrugs of monomethyl fumarate (mmf)
ES2686721T3 (es) * 2013-12-05 2018-10-19 Ratiopharm Gmbh Derivados de ácido tartárico
US9096537B1 (en) 2014-12-31 2015-08-04 Mahesh Kandula Compositions and methods for the treatment of mucositis
WO2016110865A1 (en) 2015-01-06 2016-07-14 Cellix Bio Private Limited Compositions and methods for the treatment of inflammation and pain
NZ723269A (en) * 2014-02-24 2017-04-28 Alkermes Pharma Ireland Ltd Sulfonamide and sulfinamide prodrugs of fumarates and their use in treating various diseases
US9796659B2 (en) * 2014-02-27 2017-10-24 Ratiopharm Gmbh Derivatives of polyhydroxy compounds
US9636318B2 (en) 2015-08-31 2017-05-02 Banner Life Sciences Llc Fumarate ester dosage forms
US9326947B1 (en) 2014-02-28 2016-05-03 Banner Life Sciences Llc Controlled release fumarate esters
CA2939990C (en) 2014-02-28 2018-07-10 Banner Life Sciences Llc Controlled release enteric soft capsules of fumarate esters
US10098863B2 (en) 2014-02-28 2018-10-16 Banner Life Sciences Llc Fumarate esters
US9999672B2 (en) 2014-03-24 2018-06-19 Xenoport, Inc. Pharmaceutical compositions of fumaric acid esters
HUE050165T2 (hu) * 2014-04-17 2020-11-30 Wolfgang Albrecht Etilén-glikolok MMF származékai
WO2015172083A1 (en) 2014-05-08 2015-11-12 Biogen Ma Inc. Dimethylfumarate and prodrugs for treatment of multiple sclerosis
ES2775433T3 (es) 2014-08-04 2020-07-27 Rigel Pharmaceuticals Inc Análogos de fumarato y sus usos en el tratamiento de una enfermedad autoinmunitaria o una enfermedad inflamatoria
WO2016046835A1 (en) 2014-09-26 2016-03-31 Cellix Bio Private Limited Compositions and methods for the treatment of epilepsy and neurological disorders
CN107207403A (zh) 2014-09-29 2017-09-26 塞尔利克斯生物私人有限公司 用于治疗多发性硬化的组合物和方法
WO2016061393A1 (en) 2014-10-15 2016-04-21 Xenoport, Inc. Fumarate compounds, pharmaceutical compositions, and methods of use
SG11201703369WA (en) 2014-10-27 2017-05-30 Cellix Bio Private Ltd Three component salts of fumaric acid monomethyl ester with piperazine or ethylene diamine for the treatment of multiple sclerosis
US9173877B1 (en) 2014-11-05 2015-11-03 Cellix Bio Private Limited Compositions and methods for the treatment of local pain
US9150557B1 (en) 2014-11-05 2015-10-06 Cellix Bio Private Limited Compositions and methods for the treatment of hyperglycemia
US9284287B1 (en) 2014-11-05 2016-03-15 Cellix Bio Private Limited Compositions and methods for the suppression of carbonic anhydrase activity
US9321716B1 (en) 2014-11-05 2016-04-26 Cellix Bio Private Limited Compositions and methods for the treatment of metabolic syndrome
US10208014B2 (en) 2014-11-05 2019-02-19 Cellix Bio Private Limited Compositions and methods for the treatment of neurological disorders
US9290486B1 (en) 2014-11-05 2016-03-22 Cellix Bio Private Limited Compositions and methods for the treatment of epilepsy
US9175008B1 (en) 2014-11-05 2015-11-03 Cellix Bio Private Limited Prodrugs of anti-platelet agents
MA40985A (fr) 2014-11-17 2017-09-26 Biogen Ma Inc Méthodes de traitement de la sclérose en plaques
EP3226855A1 (en) * 2014-12-01 2017-10-11 Cellix Bio Private Limited Compositions and methods for the treatment of multiple sclerosis
US9932294B2 (en) 2014-12-01 2018-04-03 Cellix Bio Private Limited Compositions and methods for the treatment of multiple sclerosis
MA41139A (fr) * 2014-12-11 2017-10-17 Actelion Pharmaceuticals Ltd Combinaison pharmaceutique comportant un agoniste sélectif du récepteur sip1
US9206111B1 (en) 2014-12-17 2015-12-08 Cellix Bio Private Limited Compositions and methods for the treatment of neurological diseases
US9409872B1 (en) * 2015-02-16 2016-08-09 Mark Quang Nguyen Fumarate compounds, pharmaceutical compositions thereof, and methods of use
MA41785A (fr) 2015-03-20 2018-01-23 Biogen Ma Inc Procédés et compositions pour l'administration intraveineuse de fumarates pour le traitement de maladies neurologiques
JP6487752B2 (ja) * 2015-03-31 2019-03-20 大阪瓦斯株式会社 ジカルボン酸又はエステル及びそれを用いた樹脂並びにそれらの製造方法
US9598354B2 (en) * 2015-05-03 2017-03-21 Mark Quang Nguyen Fumarate compounds, pharmaceutical compositions thereof, and methods of use
WO2016182898A1 (en) * 2015-05-08 2016-11-17 Xenoport, Inc. Methods of use for monomethyl fumarate and prodrugs thereof
US10213411B2 (en) 2015-08-27 2019-02-26 Vijaykumar Rajasekhar Use of prodrugs of fumarates in treating heart failure diseases
WO2017108960A1 (en) * 2015-12-22 2017-06-29 Ratiopharm Gmbh Method for producing monomethyl fumarate compounds
US10463642B2 (en) 2016-02-01 2019-11-05 Vijaykumar Rajasekhar Methods of treating heart failure diseases using prodrugs of methyl hydrogen fumarate
WO2018087605A1 (en) * 2016-11-11 2018-05-17 Cellix Bio Private Limited Compositions and methods for the treatment of gastrointestinal polyps
US10703723B2 (en) 2017-03-09 2020-07-07 Truly Translational Sweden Ab Prodrugs of sulfasalazine, pharmaceutical compositions thereof and their use in the treatment of autoimmune disease
CN111566084B (zh) * 2017-09-05 2022-12-20 北京强新生物科技有限公司 中枢神经系统疾病的新疗法
US11439617B2 (en) * 2017-10-16 2022-09-13 Dynamic Biologics Inc. Polymeric compositions of monomethyl fumarate and their use in treating relapsing remitting multiple sclerosis and psoriasis
CN108358852B (zh) * 2018-01-25 2021-07-20 于磊 Sglt2蛋白的抑制剂以及应用
WO2020094767A1 (en) 2018-11-08 2020-05-14 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of nrf2 activators for the treatment of staphylococcus aureus infections
KR20210100120A (ko) * 2018-12-06 2021-08-13 플래그쉽 파이어니어링 이노베이션스 브이, 인크. 모노메틸 푸마르산염-담체 접합체 및 그 사용 방법
KR20200094485A (ko) 2019-01-30 2020-08-07 (주)애거슨바이오 모노메틸 푸마레이트 전구체 약물 화합물 및 이들의 약학적 조성물
KR20200101200A (ko) 2019-02-19 2020-08-27 틴트리바이오 (주) 모노메틸 푸마레이트 유도체 및 이들의 약학적 조성물
CA3175830A1 (en) * 2019-04-17 2020-10-22 Sundeep Dugar Prodrugs of monomethyl fumarate
US11903918B2 (en) 2020-01-10 2024-02-20 Banner Life Sciences Llc Fumarate ester dosage forms with enhanced gastrointestinal tolerability
MX2022010962A (es) 2020-03-06 2022-10-07 Actelion Pharmaceuticals Ltd Metodos para ralentizar la perdida de volumen cerebral.
AU2021235760A1 (en) * 2020-03-13 2022-10-20 The Board Of Regents Of The University Of Texas System Treatment of disorders associated with oxidative stress and compounds for same
EP4200275A2 (en) * 2020-08-21 2023-06-28 Sitryx Therapeutics Limited Fumarate derivatives and their medical use
WO2023062511A1 (en) 2021-10-11 2023-04-20 Actelion Pharmaceuticals Ltd Methods of treating multiple sclerosis
WO2023152290A1 (en) 2022-02-11 2023-08-17 Actelion Pharmaceuticals Ltd Methods of slowing an increase in brain ventricular volume
WO2024047248A1 (en) 2022-09-02 2024-03-07 Institut National de la Santé et de la Recherche Médicale Use of nrf2 activators for the treatment of cerebral small vessel disease
CN116307280B (zh) * 2023-05-18 2023-08-01 成都理工大学 一种酸性气藏气井储层硫堵损伤量化评估方法

Family Cites Families (113)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3139395A (en) 1961-01-09 1964-06-30 American Cyanamid Co Photodimerization of fumaric acid derivatives
DE1165586B (de) 1961-07-13 1964-03-19 Dr Walter Schliesser Verfahren zur Herstellung von Fumarsaeuremonoalkylestern durch Isomerisieren von Maleinsaeurehalbestern
US3336364A (en) 1964-05-19 1967-08-15 Monsanto Co Di(allyloxymethyl)butyl bis esters
GB1153927A (en) 1966-08-25 1969-06-04 Wilhelm Hoerrmann Medicinal Composition Suitable For Treating Diseases Of The Retina
DE2163060A1 (de) 1971-12-18 1973-06-20 Basf Ag Waesserige dispersionen von mischpolymerisaten von monoestern olefinisch ungesaettigter dicarbonsaeuren
JPS60181047U (ja) 1984-05-10 1985-12-02 九州日本電気株式会社 リ−ドフレ−ム
CH664150A5 (de) 1985-01-15 1988-02-15 Peter Paul Prof Dr Speiser Fumarsaeureprodrug, verfahren zu seiner herstellung und dieses enthaltende darreichungsformen.
US5149695A (en) 1985-01-15 1992-09-22 Speiser Peter P Fumaric acid derivatives, process for the production thereof and pharmaceutical compositions containing same
DE3617626A1 (de) 1986-05-26 1987-12-03 Bayer Ag Substituierte 6-hydroxymethyl-carbapenem-antibiotika, verfahren zu ihrer herstellung und ihre verwendung
DK406686D0 (da) 1986-08-26 1986-08-26 Hans Bundgaard Carboxylsyrederivater
US4959389A (en) 1987-10-19 1990-09-25 Speiser Peter P Pharmaceutical preparation for the treatment of psoriatic arthritis
US5424332A (en) 1987-10-19 1995-06-13 Speiser; Peter P. Pharmaceutical composition and process for the production thereof
PL153592B1 (pl) 1988-07-08 1991-05-31 Politechnika Wroclawska SPOSÓB OTRZYMYWANIA NOWEGO 2-/2'-ffYDROKSY-3'-/l"-KARBONYLOKSY-2"- KARBOBUTOKSY-E-ETENO/ACBTAMIDOMETYLO-5 *-METYLOFENYLO/-2H-BENZOTRlAZOLU-1, 2,3
JP2850471B2 (ja) 1990-04-11 1999-01-27 日本油脂株式会社 不飽和ジカルボン酸モノエステルの製造方法
PH31064A (en) 1990-09-07 1998-02-05 Nycomed As Of Nycoveten Polymers containing diester units.
JP2964607B2 (ja) * 1990-10-11 1999-10-18 日産自動車株式会社 油圧供給装置
US5145684A (en) 1991-01-25 1992-09-08 Sterling Drug Inc. Surface modified drug nanoparticles
US5932214A (en) 1994-08-11 1999-08-03 Biogen, Inc. Treatment for inflammatory bowel disease with VLA-4 blockers
CH681891A5 (ru) 1992-10-09 1993-06-15 Marigen Sa
GB9411115D0 (en) 1994-06-03 1994-07-27 Secr Defence Stabilisation of photosensitive material
WO1996036613A1 (fr) 1995-05-19 1996-11-21 Nippon Soda Co., Ltd. Derives d'acides benzoiques substitues, procede de production desdits derives et herbicides
US6130248A (en) 1996-12-30 2000-10-10 Bar-Ilan University Tricarboxylic acid-containing oxyalkyl esters and uses thereof
AU5617398A (en) 1996-12-30 1998-07-31 Beacon Laboratories L.L.C. Tricarboxylic acid-containing oxyalkyl esters and uses thereof
DE19721099C2 (de) 1997-05-20 1999-12-02 Fumapharm Ag Muri Verwendung von Fumarsäurederivaten
SE9702000D0 (sv) 1997-05-28 1997-05-28 Astra Ab New pharmaceutical formulation
DE19814358C2 (de) * 1998-03-31 2002-01-17 Fumapharm Ag Muri Verwendung von Alkylhydrogenfumaraten zur Behandlung von Psoriasis, psoriatischer Arthritis, Neurodermitis und Enteritis regionalis Crohn
US6126949A (en) 1998-04-06 2000-10-03 Bernel Chemical Company, Inc. Di-behenyl fumarate and its use in dermatological products
CA2333571A1 (en) 1998-05-29 1999-12-09 Infineum Usa L.P. Wax crystal modifiers formed from dialkyl phenyl fumarate
ES2228078T3 (es) 1998-08-18 2005-04-01 Takara Bio Inc. Remedios o preventivos que contienen compuestos de ciclopentenona como ingrediente activo.
DE19839566C2 (de) * 1998-08-31 2002-01-17 Fumapharm Ag Muri Verwendung von Fumarsäurederivaten in der Transplantationsmedizin
DE19848260C2 (de) 1998-10-20 2002-01-17 Fumapharm Ag Muri Fumarsäure-Mikrotabletten
DE19853487A1 (de) 1998-11-19 2000-05-25 Fumapharm Ag Muri Verwendung von Dialkylfumaraten
JP2001158760A (ja) 1999-12-01 2001-06-12 Nisso Yuka Kogyo Kk フマル酸モノアルキルエステルおよびそのナトリウム塩の製造法
SE9904850D0 (sv) 1999-12-30 1999-12-30 Pharmacia & Upjohn Ab Novel process and intermediates
DE10000577A1 (de) 2000-01-10 2001-07-26 Fumapharm Ag Muri Verwendung von Fumarsäurederivaten zur Behandlung mitochondrialer Krankheiten
EP1130112A1 (en) 2000-02-24 2001-09-05 Epidauros Biotechnologie AG Method for detecting the presence of at least one single allele of a deletion mutant
RS52083B (sr) 2001-01-12 2012-06-30 Fumapharm Ag Amidi fumarne kiseline
DE10101307A1 (de) 2001-01-12 2002-08-01 Fumapharm Ag Muri Fumarsäurederivate als NF-kappaB-Inhibitor
AR036312A1 (es) 2001-08-31 2004-08-25 Novartis Ag Composicion farmaceutica
US6613800B1 (en) 2001-12-03 2003-09-02 Steven A. Smith Method and compositions for treating psoriasis, eczema, seborrhea and arthritis
AU2003211560A1 (en) 2002-02-20 2003-09-09 Ajinomoto Co., Inc. Novel phenylalanine derivative
DE10217314A1 (de) 2002-04-18 2003-11-13 Fumapharm Ag Muri Carbocyclische und Oxacarboncyclische Fumarsäure-Oligomere
US6709868B2 (en) 2002-05-20 2004-03-23 Portascience Inc. Method and apparatus for measuring white blood cell count
US20040102525A1 (en) 2002-05-22 2004-05-27 Kozachuk Walter E. Compositions and methods of treating neurological disease and providing neuroprotection
US7959914B2 (en) 2003-05-16 2011-06-14 Acorda Therapeutics, Inc. Methods of reducing extravasation of inflammatory cells
GB0320441D0 (en) 2003-09-02 2003-10-01 Givaudan Sa Organic compounds
DE10360869A1 (de) 2003-09-09 2005-04-07 Fumapharm Ag Verwendung von Fumarsäurederivaten zur Therapie der Herzinsuffizienz, der Hyperkeratose und von Asthma
EP1663197B1 (en) * 2003-09-09 2007-12-05 Fumapharm AG The use of fumaric acid derivatives for treating cardiac insufficiency, and asthma
DE10342423A1 (de) 2003-09-13 2005-04-14 Heidland, August, Prof. Dr.med. Dr.h.c. Verwendung von Fumarsäurederivaten zur Prophylaxe und zur Behandlung von Genomschäden
TW200517106A (en) 2003-10-29 2005-06-01 Wyeth Corp Sustained release pharmaceutical compositions
US20050096369A1 (en) 2003-11-04 2005-05-05 Hoang Ba X. Compositions and methods for treating cellular proliferation disorders
CN100537513C (zh) 2004-09-23 2009-09-09 李文佳 反丁烯二酸单甲酯的制备工艺
LT2801354T (lt) 2004-10-08 2017-06-26 Forward Pharma A/S Kontroliuojamo atpalaidavimo farmacinės kompozicijos, apimančios fumaro rūgšties esterį
TWI279403B (en) 2004-10-20 2007-04-21 Eternal Chemical Co Ltd Cyclobutanetetracarboxylate compound and preparation method thereof
EP1812374A1 (en) 2004-11-10 2007-08-01 Aditech Pharma AB Novel salts of fumaric acid monoalkylesters and their pharmaceutical use
US20080004344A1 (en) 2004-11-10 2008-01-03 Aditech Pharma Ab Novel Salts of Fumaric Acid Monoalkylesters and Their Pharmaceutical Use
DE102005022845A1 (de) 2005-05-18 2006-11-23 Fumapharm Ag Thiobernsteinsäurederivate und deren Verwendung
US20060269925A1 (en) 2005-05-25 2006-11-30 The General Hospital Corporation Methods for determining glutathione S-transferase theta-1 genotype
EP2186819A1 (en) * 2005-07-07 2010-05-19 Aditech Pharma AG Novel glucopyranose esters and glucofuranose esters of alkyl- fumarates and their pharmaceutical use
WO2007006307A2 (en) 2005-07-07 2007-01-18 Aditech Pharma Ab Novel salts of fumaric acid monoalkylesters and their pharmaceutical use
WO2007042035A2 (en) 2005-10-07 2007-04-19 Aditech Pharma Ab Combination therapy with fumaric acid esters for the treatment of autoimmune and/or inflammatory disorders
JP2009510137A (ja) 2005-10-07 2009-03-12 アディテック・ファルマ・アクチボラゲット フマル酸エステルを含む制御放出医薬組成物
BRPI0708644A2 (pt) * 2006-03-07 2011-06-07 Bristol-Myers Squibb Company compostos de pró-fármaco de anilina de pirrolotriazina úteis como inibidores de cinase
NZ572531A (en) 2006-05-05 2011-09-30 Univ Michigan Bivalent smac mimetics and the uses thereof
US20080089861A1 (en) 2006-07-10 2008-04-17 Went Gregory T Combination therapy for treatment of demyelinating conditions
HRP20220902T3 (hr) 2007-02-08 2022-10-14 Biogen Ma Inc. Pripravci i njihova upotreba u liječenju multiple skleroze
HUE032251T2 (en) 2007-02-08 2017-09-28 Biogen Ma Inc Neuroprotection in demyelinating diseases
EP1985697A1 (en) 2007-04-27 2008-10-29 AM-Pharma B.V. Modified phosphatases
ES2584509T3 (es) 2007-08-21 2016-09-28 Midwestern University Composiciones para el tratamiento del ictus o accidente cerebrovascular con un agonista del receptor de endotelina B
CN101318901A (zh) 2008-06-17 2008-12-10 健雄职业技术学院 一种富马酸二甲酯的合成新工艺
US20140193386A1 (en) 2008-06-18 2014-07-10 Lifebond Ltd. Method for enzymatic cross-linking of a protein
MX2011001341A (es) 2008-08-19 2011-03-29 Xenoport Inc Prodrogas de metil hidrogeno fumarato, sus composiciones farmaceuticas, y metodos de uso.
WO2010047775A2 (en) 2008-10-20 2010-04-29 Xenoport, Inc. Methods of synthesizing a levodopa ester prodrug
JP5608167B2 (ja) 2008-10-23 2014-10-15 ヘンケル コーポレイション 加工デンプンを含む医薬ペレット、およびそれの治療への応用
KR20100052262A (ko) 2008-11-10 2010-05-19 (주)아모레퍼시픽 난용성 약물의 나노입자를 포함하는 분말의 제조방법, 그에의해 제조된 분말 및 이를 포함하는 약학적 조성물
US20120034274A1 (en) 2009-01-09 2012-02-09 Forward Pharma A/S Pharmaceutical composition comprising one or more fumaric acid esters
US8906420B2 (en) 2009-01-09 2014-12-09 Forward Pharma A/S Pharmaceutical formulation comprising one or more fumaric acid esters in an erosion matrix
AU2010221167B2 (en) 2009-03-06 2014-04-03 Xenoport, Inc. Oral dosage forms having a high loading of a gabapentin prodrug
US20100260755A1 (en) 2009-04-09 2010-10-14 Medicinova, Inc. Ibudilast and immunomodulators combination
EP3466420A1 (en) 2009-04-29 2019-04-10 Biogen MA Inc. Dimethyl fumarate for the treatment of friedreich ataxia
EP2343075A1 (en) 2010-01-04 2011-07-13 Neurotec Pharma, S.L. Diazoxide for use in the treatment a central nervous system (CNS) autoimmune demyelinating disease
CN101774913B (zh) 2010-01-08 2013-05-29 河南大学 一种富马酸单甲酯的制备方法
NZ601698A (en) 2010-01-08 2015-04-24 Catabasis Pharmaceuticals Inc Fatty acid fumarate derivatives and their uses
SG195049A1 (en) 2011-05-26 2013-12-30 Biogen Idec Inc Methods of treating multiple sclerosis and preserving and/or increasing myelin content
US9422226B2 (en) 2011-06-08 2016-08-23 Biogen Ma Inc. Process for preparing high purity and crystalline dimethyl fumarate
US20140308244A1 (en) 2011-08-08 2014-10-16 The Board Of Trustees Of The Leland Stanford Junior University Combination Therapy for Treatment of Inflammatory Demyelinating Disease
PL2751279T3 (pl) 2011-08-31 2018-03-30 St. Jude Children's Research Hospital Sposoby i kompozycje do wykrywania poziomu aktywności lizosomalnej egzocytozy i sposoby zastosowania
RU2014125430A (ru) 2011-11-24 2015-12-27 Синтон Бв Контролируемое высвобождение частиц, содержащих диметилфумарат
EP2791181A4 (en) 2011-12-16 2015-08-05 Biogen Ma Inc SILICONE-CONTAINING FUMIC ACID ESTERS
US20130158077A1 (en) 2011-12-19 2013-06-20 Ares Trading S.A. Pharmaceutical compositions
JP5918395B2 (ja) 2012-02-07 2016-05-18 ゼノポート，インコーポレイティド モルホリノアルキルフマレート化合物、医薬組成物及び使用方法
CN104220061A (zh) 2012-02-07 2014-12-17 比奥根艾迪克依蒙菲利亚公司 含有富马酸二甲酯的药物组合物
JP6236406B2 (ja) 2012-03-07 2017-11-22 アミカス セラピューティックス インコーポレイテッド ポンペ病の処置のための高濃度α−グルコシダーゼ組成物
US20130259856A1 (en) 2012-03-27 2013-10-03 Teva Pharmaceutical Industries, Ltd. Treatment of multiple sclerosis with combination of laquinimod and dimethyl fumarate
JP2015519371A (ja) 2012-05-30 2015-07-09 ゼノポート，インコーポレイティド フマル酸水素メチルのプロドラッグを用いた多発性硬化症及び乾癬の治療
EP2692343A1 (en) 2012-08-03 2014-02-05 Forward Pharma A/S Combination therapy for treatment of multiple sclerosis
US20140057918A1 (en) 2012-08-22 2014-02-27 Xenoport, Inc. Methods of Use for Monomethyl Fumarate and Prodrugs Thereof
JP2015526476A (ja) 2012-08-22 2015-09-10 ゼノポート，インコーポレイティド メチル水素フマレートの経口剤形およびそのプロドラッグ
US10945984B2 (en) 2012-08-22 2021-03-16 Arbor Pharmaceuticals, Llc Methods of administering monomethyl fumarate and prodrugs thereof having reduced side effects
WO2014071371A1 (en) 2012-11-05 2014-05-08 Xenoport, Inc. Cocrystals of (n,n-diethylcarbamoyl)methyl methyl (2e)but-2-ene-1,4-dioate
AR094277A1 (es) 2012-12-21 2015-07-22 Biogen Idec Inc Derivados de fumarato sustituidos con deuterio
EP2934507B1 (en) 2012-12-21 2017-05-31 ratiopharm GmbH Prodrugs of monomethyl fumarate (mmf)
US8669281B1 (en) 2013-03-14 2014-03-11 Alkermes Pharma Ireland Limited Prodrugs of fumarates and their use in treating various diseases
PT2970101T (pt) 2013-03-14 2018-10-04 Alkermes Pharma Ireland Ltd Pró-fármacos de fumaratos e seu uso no tratamento de várias doenças
WO2014143146A1 (en) 2013-03-15 2014-09-18 Xenoport, Inc. Methods of administering monomethyl fumarate
US10179118B2 (en) 2013-03-24 2019-01-15 Arbor Pharmaceuticals, Llc Pharmaceutical compositions of dimethyl fumarate
WO2014190056A2 (en) 2013-05-21 2014-11-27 Biogen Idec Ma Inc. Prodrugs and drugs
WO2014197860A1 (en) 2013-06-07 2014-12-11 Xenoport, Inc. Method of making monomethyl fumarate
US9421182B2 (en) 2013-06-21 2016-08-23 Xenoport, Inc. Cocrystals of dimethyl fumarate
CA2919381A1 (en) 2013-08-01 2015-02-05 Xenoport, Inc. Methods of administering monomethyl fumarate and prodrugs thereof having reduced side effects
JP2016528302A (ja) 2013-08-26 2016-09-15 フォーワード・ファルマ・アクティーゼルスカブＦｏｒｗａｒｄ Ｐｈａｒｍａ Ａ／Ｓ 低１日用量で投与するためのフマル酸ジメチルを含む医薬組成物
JP2016534133A (ja) 2013-09-06 2016-11-04 ゼノポート，インコーポレイティド （ｎ，ｎ−ジエチルカルバモイル）メチル メチル（２ｅ）ブト−２−エン−１，４−ジオエートの結晶形態、その合成方法及び使用
WO2015042294A1 (en) 2013-09-18 2015-03-26 Xenoport, Inc. Nanoparticle compositions of dimethyl fumarate

Also Published As

Publication number Publication date
RU2554347C2 (ru) 2015-06-27
CA2806444C (en) 2016-02-23
MX2011001341A (es) 2011-03-29
US20150197486A9 (en) 2015-07-16
PT2334378E (pt) 2014-07-16
DK2334378T3 (da) 2014-07-07
US8785443B2 (en) 2014-07-22
EP2334378B1 (en) 2014-04-09
EP2650279A2 (en) 2013-10-16
US20120157523A1 (en) 2012-06-21
PL2334378T3 (pl) 2014-09-30
US9452972B2 (en) 2016-09-27
ES2477884T3 (es) 2014-07-18
JP2012500285A (ja) 2012-01-05
IL210579A (en) 2015-05-31
US20100048651A1 (en) 2010-02-25
AU2009282888A1 (en) 2010-02-25
AU2009282888B2 (en) 2013-07-11
CY1115203T1 (el) 2017-01-04
US8148414B2 (en) 2012-04-03
US8778991B2 (en) 2014-07-15
WO2010022177A2 (en) 2010-02-25
CN102123763A (zh) 2011-07-13
CA2730478C (en) 2014-04-15
EP2650279A3 (en) 2014-02-12
CA2806444A1 (en) 2010-02-25
HK1158563A1 (en) 2012-07-20
JP5670331B2 (ja) 2015-02-18
HRP20140640T1 (hr) 2014-11-21
NZ590746A (en) 2012-10-26
IL210579A0 (en) 2011-03-31
AU2009282888C1 (en) 2014-01-23
US20140329818A1 (en) 2014-11-06
IL238327A0 (en) 2015-06-30
WO2010022177A3 (en) 2010-10-21
NZ608196A (en) 2014-09-26
EP2334378A2 (en) 2011-06-22
CA2730478A1 (en) 2010-02-25
US20120095003A1 (en) 2012-04-19
ZA201100599B (en) 2014-03-26
SI2334378T1 (sl) 2014-07-31
NZ602496A (en) 2013-09-27
CN102123763B (zh) 2014-10-08

Similar Documents

Publication Publication Date Title
RU2011110435A (ru) Пролекарства метилгидрофумарата, фармацетические композиции с ними и способы применения
RU2361860C2 (ru) Новые замещенные 3-сера-индолы
RU2335493C2 (ru) Производные хинолина в качестве ингибиторов фосфодиэстеразы
RU2315041C2 (ru) Производные 2,6-хинолинила и 2,6-нафтила, фармацевтические композиции на их основе, их применение в качестве ингибиторов vla-4 и промежуточные соединения
RU2009148673A (ru) Производные пиразинона и их применение для лечения легочных заболеваний
JP2014502979A5 (ru)
JP2004506632A5 (ru)
RU2007119427A (ru) Соединения, являющиеся ингибиторами гликогенфосфорилазы, и фармацевтические композиции на их основе
CA2565813A1 (en) Substituted methyl aryl or heteroaryl amide compounds
JP2013525318A5 (ru)
RU2000118792A (ru) ПРОИЗВОДНЫЕ БЕНЗАМИДИНА В КАЧЕСТВЕ ИНГИБИТОРОВ ФАКТОРА СВЕРТЫВАНИЯ КРОВИ Хa
JP2008509166A5 (ru)
PE20010987A1 (es) Inhibidores no peptidicos de la union celular dependiente de vla-4 utiles en el tratamiento de enfermedades inflamatorias, autoinmunes y respiratorias
JP2010526146A5 (ru)
JP2011520815A5 (ru)
RU2012116877A (ru) Соединения 2-пиридона, применяемые в качестве ингибиторов нейтрофильной эластазы
JP2007519619A5 (ru)
JP2013517283A5 (ru)
RU2008129723A (ru) Ингибиторы ccr9 активности
RU2012131341A (ru) Индол-пиперидинилбензиламины как ингибиторы бета-триптазы
EA200802173A1 (ru) Производные терфенила для лечения болезни альцгеймера
JP2009504793A5 (ru)
RU2008129641A (ru) Ингибиторы ccr9 активности
RU2010142936A (ru) НОВЫЕ ПРОИЗВОДНЫЕ ПИПЕРАЗИНА КАК ИНГИБИТОРЫ СТЕАРОИЛ-КоА ДЕСАТУРАЗЫ
RU2008123811A (ru) Хиназолины, используемые в качестве модуляторов потенциалзависимых ионных каналов

Legal Events

Date Code Title Description
MM4A The patent is invalid due to non-payment of fees

Effective date: 20170820