RU2021111681A - Нейроактивные стероиды, композиции и их применение - Google Patents
Нейроактивные стероиды, композиции и их применение Download PDFInfo
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- RU2021111681A RU2021111681A RU2021111681A RU2021111681A RU2021111681A RU 2021111681 A RU2021111681 A RU 2021111681A RU 2021111681 A RU2021111681 A RU 2021111681A RU 2021111681 A RU2021111681 A RU 2021111681A RU 2021111681 A RU2021111681 A RU 2021111681A
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- hydroxycholesterol
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- 150000003431 steroids Chemical class 0.000 title claims 2
- 239000000203 mixture Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 8
- 238000000034 method Methods 0.000 claims 7
- IOWMKBFJCNLRTC-XWXSNNQWSA-N (24S)-24-hydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@H](O)C(C)C)[C@@]1(C)CC2 IOWMKBFJCNLRTC-XWXSNNQWSA-N 0.000 claims 6
- IOWMKBFJCNLRTC-UHFFFAOYSA-N 24S-hydroxycholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(O)C(C)C)C1(C)CC2 IOWMKBFJCNLRTC-UHFFFAOYSA-N 0.000 claims 6
- 239000000523 sample Substances 0.000 claims 6
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims 4
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims 4
- 238000011156 evaluation Methods 0.000 claims 4
- 230000004044 response Effects 0.000 claims 4
- 102000004190 Enzymes Human genes 0.000 claims 2
- 108090000790 Enzymes Proteins 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 229940126662 negative allosteric modulator Drugs 0.000 claims 2
- 229940126027 positive allosteric modulator Drugs 0.000 claims 2
- 102100038697 24-hydroxycholesterol 7-alpha-hydroxylase Human genes 0.000 claims 1
- 108030007272 24-hydroxycholesterol 7-alpha-hydroxylases Proteins 0.000 claims 1
- 102000023526 Cytochrome P450 Family 46 Human genes 0.000 claims 1
- 108010036233 Cytochrome P450 Family 46 Proteins 0.000 claims 1
- 208000003870 Drug Overdose Diseases 0.000 claims 1
- 206010033296 Overdoses Diseases 0.000 claims 1
- 229930182558 Sterol Natural products 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 239000005557 antagonist Substances 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 231100000725 drug overdose Toxicity 0.000 claims 1
- 206010027175 memory impairment Diseases 0.000 claims 1
- 239000013610 patient sample Substances 0.000 claims 1
- 150000003432 sterols Chemical class 0.000 claims 1
- 235000003702 sterols Nutrition 0.000 claims 1
Classifications
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
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- A—HUMAN NECESSITIES
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- 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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- A61P39/00—General protective or antinoxious agents
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- A—HUMAN NECESSITIES
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C01B3/00—Hydrogen; Gaseous mixtures containing hydrogen; Separation of hydrogen from mixtures containing it; Purification of hydrogen
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- C01B3/04—Production of hydrogen or of gaseous mixtures containing a substantial proportion of hydrogen by decomposition of inorganic compounds, e.g. ammonia
- C01B3/047—Decomposition of ammonia
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- C07J1/0022—Androstane derivatives substituted in position 17 beta, not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
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- C07J7/0065—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by an OH group free esterified or etherified
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- F02—COMBUSTION ENGINES; HOT-GAS OR COMBUSTION-PRODUCT ENGINE PLANTS
- F02B—INTERNAL-COMBUSTION PISTON ENGINES; COMBUSTION ENGINES IN GENERAL
- F02B43/00—Engines characterised by operating on gaseous fuels; Plants including such engines
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- F02B43/12—Methods of operating
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
- G01N24/08—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using nuclear magnetic resonance
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
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- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
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- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0003—Androstane derivatives
- C07J1/0011—Androstane derivatives substituted in position 17 by a keto group
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- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0003—Androstane derivatives
- C07J1/0018—Androstane derivatives substituted in position 17 beta, not substituted in position 17 alfa
- C07J1/0022—Androstane derivatives substituted in position 17 beta, not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
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- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
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- C07J41/0061—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives one of the carbon atoms being part of an amide group
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- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
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- C07J7/002—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa not substituted in position 16
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- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
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Claims (9)
1. Способ оценки или лечения пациента, например пациента с описанным здесь нарушением, включающий
a) необязательно получение образца пациента;
b) получение оценки и/или оценку образца на изменение в уровне 24(S)-гидроксихолестерина по сравнению со стандартным образцом.
2. Способ по п.1, дополнительно включающий введение пациенту (например, в ответ на оценку образца) эффективного количества 24(S)-гидроксихолестерина или структурно родственного стерина или стероида, оксистерина, агониста NMDAR или позитивного аллостерического модулятора (PAM) NMDAR, или описанного здесь соединения, такого как соединение формулы (I).
3. Способ по п.1, дополнительно включающий введение пациенту (например, в ответ на оценку образца) эффективного количества антагониста NMDAR или негативного аллостерического модулятора (NAM) NMDAR.
4. Способ по п.1, дополнительно включающий введение пациенту (например, в ответ на оценку образца) эффективного количества соединения, которое дополняет (например повышает) эндогенную активность или количество 24(s)-гидроксихолестерина (например соединения, ингибирующего фермент, который метаболизирует 24(s)-гидроксихолестерин (например соединения, ингибирующего 24-гидроксихолестерин-7-альфа-гидроксилазу (CYP39))).
5. Способ по п.1, дополнительно включающий введение пациенту (например, в ответ на оценку образца) эффективного количества соединения, которое снижает эндогенную активность или количество 24(s)-гидроксихолестерина (например соединения, активирующего фермент, который продуцирует 24(s)-гидроксихолестерин (например соединения, активирующего холестерин-24(S)-гидроксилазу (CYP46))).
6. Способ по п.1, дополнительно включает лечение пациента, где пациента лечат от ухудшения памяти или для улучшения обучаемости.
7. Способ по п.1, дополнительно включает лечение пациента от передозировки наркотиками.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361780671P | 2013-03-13 | 2013-03-13 | |
US61/780,671 | 2013-03-13 |
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AU2006318349B2 (en) | 2005-11-28 | 2010-08-19 | Marinus Pharmaceuticals | Ganaxolone formulations and methods for the making and use thereof |
CN113956315A (zh) | 2011-09-08 | 2022-01-21 | 萨奇治疗股份有限公司 | 神经活性类固醇、组合物、及其用途 |
ES2886506T3 (es) | 2013-03-13 | 2021-12-20 | Sage Therapeutics Inc | Esteroides neuroactivos |
EP4306114A1 (en) * | 2014-06-18 | 2024-01-17 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
MX2017004684A (es) * | 2014-10-07 | 2017-06-30 | Sage Therapeutics Inc | Compuestos neuroactivos y metodos de uso de los mismos. |
HUE053778T2 (hu) * | 2015-07-06 | 2021-07-28 | Sage Therapeutics Inc | Oxiszterinek és ezek alkalmazása |
MA54851A (fr) * | 2015-07-06 | 2021-12-08 | Sage Therapeutics Inc | Oxystérols et leurs procédés d'utilisation |
CA2991311A1 (en) * | 2015-07-06 | 2017-01-12 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
NZ739219A (en) | 2015-07-30 | 2019-03-29 | Intercept Pharmaceuticals Inc | Methods for preparation of bile acids and derivatives thereof |
CA3001722A1 (en) | 2015-10-16 | 2017-04-20 | Marinus Pharmaceuticals, Inc. | Injectable neurosteroid formulations containing nanoparticles |
PT3436022T (pt) * | 2016-04-01 | 2022-07-04 | Sage Therapeutics Inc | Oxisteróis e métodos de utilização dos mesmos |
US10752653B2 (en) | 2016-05-06 | 2020-08-25 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
EP3481846B1 (en) | 2016-07-07 | 2021-05-12 | Sage Therapeutics, Inc. | 11-substituted 24-hydroxysterols for use in the treatment of nmda related conditions |
MX2019001669A (es) | 2016-08-11 | 2019-09-27 | Ovid Therapeutics Inc | Metodos y composiciones para el tratamiento de trastornos epilepticos. |
US10391105B2 (en) | 2016-09-09 | 2019-08-27 | Marinus Pharmaceuticals Inc. | Methods of treating certain depressive disorders and delirium tremens |
BR112019006365A2 (pt) | 2016-09-30 | 2019-08-06 | Sage Therapeutics Inc | oxisteróis substituídos c7 e métodos de utilização dos mesmos |
JP2019532079A (ja) | 2016-10-18 | 2019-11-07 | セージ セラピューティクス, インコーポレイテッド | オキシステロールおよびその使用方法 |
EP3529257B1 (en) * | 2016-10-18 | 2023-05-10 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
GB201812382D0 (en) | 2018-07-30 | 2018-09-12 | Nzp Uk Ltd | Compounds |
WO2020027344A1 (en) * | 2018-08-03 | 2020-02-06 | Takeda Pharmaceutical Company Limited | Ch24h inhibitors for mdd use |
US20210346366A1 (en) * | 2018-09-20 | 2021-11-11 | Takeda Pharmaceutical Company Limited | Ch24h inhibitors for pain use |
US11266662B2 (en) | 2018-12-07 | 2022-03-08 | Marinus Pharmaceuticals, Inc. | Ganaxolone for use in prophylaxis and treatment of postpartum depression |
WO2021026124A1 (en) | 2019-08-05 | 2021-02-11 | Marinus Pharmaceuticals, Inc. | Ganaxolone for use in treatment of status epilepticus |
CN110646626B (zh) * | 2019-09-05 | 2023-08-15 | 首都医科大学附属北京安定医院 | 24-羟基胆固醇在制备诊断或早期诊断精神分裂症的产品中的用途 |
CN110702929B (zh) * | 2019-09-05 | 2023-08-15 | 首都医科大学附属北京安定医院 | 27-羟基胆固醇在制备诊断精神分裂症的产品中的用途 |
US10857163B1 (en) | 2019-09-30 | 2020-12-08 | Athenen Therapeutics, Inc. | Compositions that preferentially potentiate subtypes of GABAA receptors and methods of use thereof |
JP2023503928A (ja) | 2019-12-06 | 2023-02-01 | マリナス ファーマシューティカルズ, インコーポレイテッド | 結節性硬化症の治療での使用のためのガナキソロン |
WO2023028278A2 (en) * | 2021-08-25 | 2023-03-02 | Sage Therapeutics, Inc. | Positive nmda-modulating compounds and methods of use thereof |
CN114409718A (zh) * | 2021-12-31 | 2022-04-29 | 湖北武当安泰药业有限公司 | 去氢表雄酮催化加氢制备表雄酮的方法 |
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EP1450816A4 (en) * | 2001-11-08 | 2008-02-13 | Univ Chicago | METHOD FOR TREATING DISORDER IN CONNECTION WITH INCREASED CHOLESTERITE CONCENTRATION |
JP2005511713A (ja) * | 2001-12-07 | 2005-04-28 | ザ・リージェンツ・オブ・ザ・ユニバーシティー・オブ・カリフォルニア | 加齢性黄斑変性についての処置 |
AU2003288231A1 (en) * | 2002-12-13 | 2004-07-09 | Bayer Healthcare Ag | Cholesterol 24-hydroxylase (cyp46) as therapeutic target for the treatment of alzheimer's disease |
WO2006037016A2 (en) * | 2004-09-27 | 2006-04-06 | The Regents Of The University Of California | Novel therapy for treatment of chronic degenerative brain diseases and nervous system injury |
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WO2008057468A1 (en) * | 2006-11-02 | 2008-05-15 | Curis, Inc. | Small organic molecule regulators of cell proliferation |
CN104892498A (zh) * | 2007-06-20 | 2015-09-09 | 奥斯拜客斯制药有限公司 | 作为纤维化抑制剂的取代的n-芳基吡啶酮 |
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US20150031655A1 (en) * | 2011-04-15 | 2015-01-29 | University Of North Dakota | Combination of liver x receptor modulator and estrogen receptor modulator for the treatment of age-related diseases |
CN113956315A (zh) * | 2011-09-08 | 2022-01-21 | 萨奇治疗股份有限公司 | 神经活性类固醇、组合物、及其用途 |
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