RU2018130727A - Органические соединения - Google Patents
Органические соединения Download PDFInfo
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- RU2018130727A RU2018130727A RU2018130727A RU2018130727A RU2018130727A RU 2018130727 A RU2018130727 A RU 2018130727A RU 2018130727 A RU2018130727 A RU 2018130727A RU 2018130727 A RU2018130727 A RU 2018130727A RU 2018130727 A RU2018130727 A RU 2018130727A
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- 150000002894 organic compounds Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 16
- 125000000217 alkyl group Chemical group 0.000 claims 11
- 150000003839 salts Chemical group 0.000 claims 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 8
- 208000035475 disorder Diseases 0.000 claims 8
- 238000000034 method Methods 0.000 claims 7
- 208000028017 Psychotic disease Diseases 0.000 claims 6
- 201000000980 schizophrenia Diseases 0.000 claims 6
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 208000011117 substance-related disease Diseases 0.000 claims 5
- 206010012289 Dementia Diseases 0.000 claims 4
- 208000018737 Parkinson disease Diseases 0.000 claims 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims 4
- 208000012902 Nervous system disease Diseases 0.000 claims 3
- 238000013019 agitation Methods 0.000 claims 3
- 206010013663 drug dependence Diseases 0.000 claims 3
- 208000019116 sleep disease Diseases 0.000 claims 3
- 208000007848 Alcoholism Diseases 0.000 claims 2
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- 208000020706 Autistic disease Diseases 0.000 claims 2
- 208000019022 Mood disease Diseases 0.000 claims 2
- 208000026251 Opioid-Related disease Diseases 0.000 claims 2
- 208000015114 central nervous system disease Diseases 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 239000011159 matrix material Substances 0.000 claims 2
- 201000005040 opiate dependence Diseases 0.000 claims 2
- 229920000642 polymer Polymers 0.000 claims 2
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 206010001497 Agitation Diseases 0.000 claims 1
- 208000019901 Anxiety disease Diseases 0.000 claims 1
- 206010003805 Autism Diseases 0.000 claims 1
- 208000020925 Bipolar disease Diseases 0.000 claims 1
- 102000004076 Dopamine D1 Receptors Human genes 0.000 claims 1
- 108090000511 Dopamine D1 Receptors Proteins 0.000 claims 1
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 1
- 208000004547 Hallucinations Diseases 0.000 claims 1
- 206010019233 Headaches Diseases 0.000 claims 1
- 206010020710 Hyperphagia Diseases 0.000 claims 1
- 208000019695 Migraine disease Diseases 0.000 claims 1
- -1 NH 2 Inorganic materials 0.000 claims 1
- 208000025966 Neurological disease Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 206010041250 Social phobia Diseases 0.000 claims 1
- 208000028552 Treatment-Resistant Depressive disease Diseases 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 230000036506 anxiety Effects 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 208000028683 bipolar I disease Diseases 0.000 claims 1
- 208000025307 bipolar depression Diseases 0.000 claims 1
- 210000003169 central nervous system Anatomy 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 230000004064 dysfunction Effects 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 230000005176 gastrointestinal motility Effects 0.000 claims 1
- 231100000869 headache Toxicity 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000004005 microsphere Substances 0.000 claims 1
- 102000051367 mu Opioid Receptors Human genes 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 235000020830 overeating Nutrition 0.000 claims 1
- 230000037361 pathway Effects 0.000 claims 1
- 239000008177 pharmaceutical agent Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- 208000020016 psychiatric disease Diseases 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 229940076279 serotonin Drugs 0.000 claims 1
- 230000000697 serotonin reuptake Effects 0.000 claims 1
- 208000012201 sexual and gender identity disease Diseases 0.000 claims 1
- 208000015891 sexual disease Diseases 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 108020001612 μ-opioid receptors Proteins 0.000 claims 1
Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/16—Peri-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- 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
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
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- 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
- A61P25/24—Antidepressants
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- 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
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- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
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- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Claims (34)
1. Соединение Формулы I:
Формула I
в которой:
X представляет собой -NH- или -N(CH3)-;
L выбран из O, NH, NRa и S;
Z представляет собой -CH(O-R1)-, -O- или -C(=O)-;
R1 представляет собой H, -C(O)-C1-21алкил (например, -C(O)-C1-5алкил, -C(O)-C6-15алкил или -C(O)-C16-21алкил), предпочтительно указанный алкил представляет собой прямую цепь, необязательно насыщенную или ненасыщенную и необязательно замещенную одной или более гидрокси или C1-22алкокси (например, этокси) группами, например, R1 представляет собой C(O)-C3алкил, -C(O)-C6алкил, -C(O)-C7алкил, -C(O)-C9алкил, -C(O)-C11алкил, -C(O)-C13алкил или -C(O)-C15алкил;
Ra представляет собой:
галоген, С1-4алкил, С2-4алкенил, С2-4алкинил или С3-6циклоалкил, каждый из которых может быть независимо замещен до трех независимо выбранных Rb-групп, например, С1-3галогеналкил или С1-3гидроксиалкил; или
арил, необязательно замещенный до пяти независимо выбранных Rb; и каждый Rb независимо выбран из H, галогена, NH2, NO2, OH, C(=O)OH, CN, SO3 и C1-4алкила;
в свободной или солевой форме;
необязательно в выделенной или очищенной свободной или солевой форме.
2. Соединение по п.1, в котором L представляет собой O.
3. Соединение по п.1 или 2, в котором Z представляет собой -CH(O-R1)-.
4. Соединение по п.1 или 2, в котором Z представляет собой -C(=O)-.
5. Соединение по п.1 или 2, в котором Z представляет собой -O-.
6. Соединение по любому из пп.1-5, в котором X представляет собой -NH-.
7. Соединение по любому из пп.1-5, в котором X представляет собой -N(CH3)-.
8. Соединение по любому из пп.1-7, в котором соединение выбрано из группы, состоящей из:
9. Соединение по любому из пп.1-7, в котором соединение выбрано из группы, состоящей из:
10. Соединение по любому из пп.1-9 в форме соли, например, в форме фармацевтически приемлемой соли.
11. Фармацевтическая композиция, содержащая соединение по любому одному из пп.1-10 в свободной или фармацевтически приемлемой солевой форме в смеси с фармацевтически приемлемым разбавителем или носителем.
12. Фармацевтическая композиция по п.11, в которой фармацевтически приемлемый разбавитель или носитель содержит полимерную матрицу.
13. Фармацевтическая композиция по п.12, в которой полимерная матрица представляет собой биоразлагаемую поли(d,l-лактид-со-гликолид) микросферу.
14. Способ лечения или профилактики расстройства центральной нервной системы, включающий введение пациенту, нуждающемуся в таком лечении, соединения по любому одному из пп.1-10 в свободной или фармацевтически приемлемой солевой форме или фармацевтической композиции по любому одному из пп.11-13.
15. Способ по п.14, в котором указанное расстройство выбрано из группы, состоящей из расстройства, выбранного из группы, состоящей из ожирения, тревожности, депрессии (например, рефрактерной депрессии, БДР или биполярной депрессии), психоза (включая психоз, связанный с деменцией, такой как галлюцинации при прогрессирующей болезни Паркинсона или параноидальные идеи), шизофрении, нарушений сна (в частности нарушений сна, связанных с шизофренией и другими психиатрическими и неврологическими заболеваниями), сексуальных расстройств, мигрени, состояний, связанных с головной болью, социальных фобий, возбуждения при деменции (например, возбуждения при болезни Альцгеймера), возбуждения при аутизме и родственных аутических расстройствах, желудочно-кишечных расстройств, таких как дисфункция моторики желудочно-кишечного тракта, и деменции, например, деменции болезни Альцгеймера или болезни Паркинсона; расстройств настроения; и наркотических зависимостей, например, опиатной зависимости и/или алкогольной зависимости или отмены наркотической или алкогольной зависимости (например, опиатной зависимости); или компульсивного переедания.
16. Способ по п.14, в котором указанное расстройство представляет собой расстройство, в которое вовлечены пути серотонина 5-НТ2А, транспортера обратного захвата серотонина (SERT), дофамина D1 и/или μ-опиоидный рецептор.
17. Способ по п.14, в котором указанное расстройство представляет собой расстройство, выбранное из следующего: (1) психоз, например, шизофрения у пациента, страдающего депрессией; (2) депрессия у пациента, страдающего психозом, например, шизофренией; (3) расстройства настроения, связанные с психозом, например, шизофренией или болезнью Паркинсона; (4) нарушения сна, связанные с психозом, например, шизофренией или болезнью Паркинсона; и (5) наркотическая зависимость, нарушения, связанные с употреблением веществ, и/или нарушения, вызванные употреблением веществ.
18. Способ по любому из пп.14-17, в котором пациент страдает расстройством, связанным с употреблением веществ вместе со вторым расстройством центральной нервной системы.
19. Соединение по любому из пп.1-10 в свободной или фармацевтически приемлемой солевой форме для применения в качестве фармацевтического средства, например, в способе по любому из пп.14-18.
20. Применение соединения по любому из пп.1-10 в свободной или фармацевтически приемлемой солевой форме или Фармацевтической Композиции по любому одному из пп.11-13 в свободной или фармацевтически приемлемой солевой форме при изготовлении лекарственного средства для лечения или профилактики расстройства центральной нервной системы, например, для применения в способе по любому из пп.14-18.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662287264P | 2016-01-26 | 2016-01-26 | |
| US62/287,264 | 2016-01-26 | ||
| US201662440130P | 2016-12-29 | 2016-12-29 | |
| US62/440,130 | 2016-12-29 | ||
| PCT/US2017/015178 WO2017132408A1 (en) | 2016-01-26 | 2017-01-26 | Organic compounds |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2020134306A Division RU2776800C2 (ru) | 2016-01-26 | 2017-01-26 | Фармацевтическая композиция и способ лечения или профилактики расстройства центральной нервной системы |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2018130727A true RU2018130727A (ru) | 2020-02-27 |
| RU2018130727A3 RU2018130727A3 (ru) | 2020-03-13 |
| RU2743513C2 RU2743513C2 (ru) | 2021-02-19 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2018130727A RU2743513C2 (ru) | 2016-01-26 | 2017-01-26 | Органические соединения |
Country Status (17)
| Country | Link |
|---|---|
| US (4) | US10245260B2 (ru) |
| EP (2) | EP3838274B1 (ru) |
| JP (3) | JP6995761B2 (ru) |
| KR (2) | KR20240170975A (ru) |
| CN (2) | CN108883111B (ru) |
| AU (1) | AU2017211791B2 (ru) |
| BR (1) | BR112018015283B1 (ru) |
| CA (1) | CA3011983A1 (ru) |
| DK (2) | DK3407888T3 (ru) |
| ES (2) | ES2969145T3 (ru) |
| HU (2) | HUE064667T2 (ru) |
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