NO308950B1 - Forbindelse, farmasøytisk preparat omfattende denne samt anvendelse derav - Google Patents
Forbindelse, farmasøytisk preparat omfattende denne samt anvendelse derav Download PDFInfo
- Publication number
- NO308950B1 NO308950B1 NO972320A NO972320A NO308950B1 NO 308950 B1 NO308950 B1 NO 308950B1 NO 972320 A NO972320 A NO 972320A NO 972320 A NO972320 A NO 972320A NO 308950 B1 NO308950 B1 NO 308950B1
- Authority
- NO
- Norway
- Prior art keywords
- pregnan
- dihydroxy
- hydroxy
- trifluoromethyl
- methyl
- Prior art date
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- 230000000946 synaptic effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- VSAISIQCTGDGPU-UHFFFAOYSA-N tetraphosphorus hexaoxide Chemical compound O1P(O2)OP3OP1OP2O3 VSAISIQCTGDGPU-UHFFFAOYSA-N 0.000 description 1
- 230000035922 thirst Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 238000006692 trifluoromethylation reaction Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
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- 239000001993 wax Substances 0.000 description 1
- 229910009112 xH2O Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/005—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 only two carbon atoms, e.g. pregnane derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- A61P25/12—Antiepileptics; Anticonvulsants for grand-mal
-
- 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
- A61P25/22—Anxiolytics
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0007—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa
- C07J5/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa not substituted in position 16
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—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
- 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
- C07J7/0015—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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—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
- 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
- C07J7/007—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 not substituted in position 17 alfa
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US34692694A | 1994-11-23 | 1994-11-23 | |
PCT/US1995/015210 WO1996016076A1 (en) | 1994-11-23 | 1995-11-22 | Androstane and pregnane series for allosteric modulation of gaba receptor |
Publications (3)
Publication Number | Publication Date |
---|---|
NO972320D0 NO972320D0 (no) | 1997-05-21 |
NO972320L NO972320L (no) | 1997-07-23 |
NO308950B1 true NO308950B1 (no) | 2000-11-20 |
Family
ID=23361616
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO972320A NO308950B1 (no) | 1994-11-23 | 1997-05-21 | Forbindelse, farmasøytisk preparat omfattende denne samt anvendelse derav |
Country Status (27)
Country | Link |
---|---|
EP (1) | EP0808325B1 (pt) |
JP (1) | JPH10509458A (pt) |
KR (1) | KR100394548B1 (pt) |
CN (1) | CN1171114A (pt) |
AP (1) | AP653A (pt) |
AT (1) | ATE198753T1 (pt) |
AU (1) | AU707486B2 (pt) |
BR (1) | BR9509764A (pt) |
CA (1) | CA2205919A1 (pt) |
CZ (1) | CZ292881B6 (pt) |
DE (1) | DE69519945T2 (pt) |
DK (1) | DK0808325T3 (pt) |
ES (1) | ES2155543T3 (pt) |
FI (1) | FI972202A (pt) |
GE (1) | GEP20002033B (pt) |
GR (1) | GR3035562T3 (pt) |
HU (1) | HUT77087A (pt) |
IL (1) | IL116108A (pt) |
IS (1) | IS4488A (pt) |
MX (1) | MX9703826A (pt) |
NO (1) | NO308950B1 (pt) |
NZ (1) | NZ298567A (pt) |
PL (1) | PL182898B1 (pt) |
PT (1) | PT808325E (pt) |
RU (1) | RU2176248C2 (pt) |
UA (1) | UA48154C2 (pt) |
WO (1) | WO1996016076A1 (pt) |
Families Citing this family (64)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5767117A (en) * | 1994-11-18 | 1998-06-16 | The General Hospital Corporation | Method for treating vascular headaches |
DE69634039T2 (de) * | 1995-06-06 | 2005-12-08 | Euro-Celtique S.A. | Steroidderivate der Androstan- und der Pregnanreihe |
US6780853B1 (en) | 1995-06-06 | 2004-08-24 | Euro-Celtique S.A. | Neuroactive steroids of the androstane and pregnane series |
US20010051599A1 (en) | 1997-05-02 | 2001-12-13 | Michael Z. Kagan | Pregnan-3-ol-20-ones |
ATE307592T1 (de) | 1998-03-11 | 2005-11-15 | Torbjoern Backstroem | Epiallopregnanolon zur behandlung von krankheiten des cns |
US8771740B2 (en) | 1999-12-20 | 2014-07-08 | Nicholas J. Kerkhof | Process for producing nanoparticles by spray drying |
AU778931B2 (en) | 1999-12-20 | 2004-12-23 | Nicholas J. Kerkhof | Process for producing nanometer particles by fluid bed spray-drying |
AR031473A1 (es) * | 2000-11-20 | 2003-09-24 | Lundbeck & Co As H | Intensificadores de gaba en el tratamiento de enfermedades relacionadas con una reducida actividad neuroesteroide |
WO2006012563A2 (en) * | 2004-07-23 | 2006-02-02 | The Regents Of The University Of California | Method for the treatment and diagnosis of certain psychiatric disorders related to the menstrual cycle |
EP2258358A3 (en) | 2005-08-26 | 2011-09-07 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
EP2275095A3 (en) | 2005-08-26 | 2011-08-17 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
JP2009512711A (ja) | 2005-10-21 | 2009-03-26 | ブレインセルス,インコーポレイティド | Pde阻害による神経新生の調節 |
CA2625210A1 (en) | 2005-10-31 | 2007-05-10 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
WO2007134136A2 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
WO2008063128A1 (en) * | 2006-11-21 | 2008-05-29 | Umecrine Ab | The use of pregnane and androstane steroids for the manufacture of a pharmaceutical composition for the treatment of cns disorders |
CN103819525A (zh) * | 2008-05-20 | 2014-05-28 | 梅克芳股份公司 | 甾族化合物 |
CN101585862B (zh) * | 2008-05-20 | 2014-12-17 | 梅克芳股份公司 | 甾族化合物 |
CN103880909A (zh) * | 2008-05-20 | 2014-06-25 | 梅克芳股份公司 | 甾族化合物 |
WO2010099217A1 (en) | 2009-02-25 | 2010-09-02 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
WO2011019821A2 (en) * | 2009-08-13 | 2011-02-17 | Marinus Pharmaceuticals, Inc. | METHOD FOR MAKING 3α-HYDROXY, 3β- METHYL-5α-PREGNAN-20-ONE (GANAXOLONE) |
RU2012133627A (ru) | 2010-01-14 | 2014-04-20 | Умекрине Муд Аб | Фармацевтическая композиция, содержащая 3-бета-гидрокси-5-альфа-прегнан-20-он, с улучшенными свойствами хранения и растворимости |
US20130245253A1 (en) * | 2010-03-26 | 2013-09-19 | Department Of Veterans Affairs | Conjugated Neuroactive Steroid Compositions And Methods Of Use |
JP2014521662A (ja) * | 2011-07-29 | 2014-08-28 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | GABAA受容体のモジュレーターとしての新規な17β−ヘテロアリール置換ステロイド |
JP6205362B2 (ja) * | 2011-09-08 | 2017-09-27 | セージ セラピューティクス, インコーポレイテッド | 神経刺激性のステロイド、組成物、およびそれらの使用 |
WO2013043985A1 (en) | 2011-09-23 | 2013-03-28 | The Regents Of The University Of California | Edible oils to enhance delivery of orally administered steroids |
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WO2016134301A2 (en) | 2015-02-20 | 2016-08-25 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
PE20180482A1 (es) | 2015-07-06 | 2018-03-07 | Sage Therapeutics Inc | Oxiesteroles y metodos de uso de los mismos |
EP3426257A4 (en) | 2016-03-08 | 2019-11-13 | Sage Therapeutics, Inc. | NEUROACTIVE STEROIDS, COMPOSITIONS AND USES THEREOF |
LT3436022T (lt) | 2016-04-01 | 2022-06-27 | Sage Therapeutics, Inc. | Oksisteroliai ir jų panaudojimo būdai |
US10752653B2 (en) | 2016-05-06 | 2020-08-25 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
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US20190233465A1 (en) | 2016-07-11 | 2019-08-01 | Sage Therapeutics, Inc. | C7, c12, and c16 substituted neuroactive steroids and their methods of use |
MA46351A (fr) | 2016-09-30 | 2021-06-02 | Sage Therapeutics Inc | Oxystérols substitués en c7 et procédés en tant que modulateurs nmda |
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JOP20210293A1 (ar) | 2019-05-31 | 2023-01-30 | Sage Therapeutics Inc | ستيرويدات ذات فعالية عصبية وتركيبات منها |
AU2020304679A1 (en) * | 2019-06-27 | 2022-01-20 | Sage Therapeutics, Inc. | Compounds for treating CNS disorders |
CA3175324A1 (en) * | 2020-03-18 | 2021-09-23 | Sage Therapeutics, Inc. | Neuroactive steroids and their methods of use |
CA3229865A1 (en) * | 2021-08-20 | 2023-02-23 | The University Of Mississippi | Allopregnanolone analogues for hiv viremia and neurotoxicity protection |
WO2023060067A1 (en) | 2021-10-04 | 2023-04-13 | Marinus Pharmaceuticals, Inc. | Amorphous solid dispersion ganaxolone formulation |
CN117801047A (zh) * | 2023-01-19 | 2024-04-02 | 北京华睿鼎信科技有限公司 | 神经甾体衍生物及其用途 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3953429A (en) * | 1970-12-17 | 1976-04-27 | Glaxo Laboratories Limited | Anaesthetic steroids of the androstance and pregnane series |
US5232917A (en) * | 1987-08-25 | 1993-08-03 | University Of Southern California | Methods, compositions, and compounds for allosteric modulation of the GABA receptor by members of the androstane and pregnane series |
US5120723A (en) * | 1987-08-25 | 1992-06-09 | University Of Southern California | Method, compositions, and compounds for modulating brain excitability |
AU2657292A (en) * | 1991-09-13 | 1993-04-27 | Cocensys, Inc. | Novel gabaa receptor with steroid binding sites |
US5371077A (en) * | 1992-08-03 | 1994-12-06 | William Marsh Rice University | Side chain derivatized 15-oxygenated sterols, methods of using them and a process for preparing them |
AU698834B2 (en) * | 1993-05-24 | 1998-11-12 | Purdue Pharma Ltd. | Methods and compositions for inducing sleep |
-
1995
- 1995-11-22 CZ CZ19971553A patent/CZ292881B6/cs not_active IP Right Cessation
- 1995-11-22 EP EP95942879A patent/EP0808325B1/en not_active Expired - Lifetime
- 1995-11-22 CA CA002205919A patent/CA2205919A1/en not_active Abandoned
- 1995-11-22 BR BR9509764A patent/BR9509764A/pt not_active Application Discontinuation
- 1995-11-22 ES ES95942879T patent/ES2155543T3/es not_active Expired - Lifetime
- 1995-11-22 DE DE69519945T patent/DE69519945T2/de not_active Expired - Fee Related
- 1995-11-22 WO PCT/US1995/015210 patent/WO1996016076A1/en active IP Right Grant
- 1995-11-22 AU AU44085/96A patent/AU707486B2/en not_active Ceased
- 1995-11-22 HU HU9701972A patent/HUT77087A/hu not_active Application Discontinuation
- 1995-11-22 AT AT95942879T patent/ATE198753T1/de not_active IP Right Cessation
- 1995-11-22 MX MX9703826A patent/MX9703826A/es not_active IP Right Cessation
- 1995-11-22 PL PL95320416A patent/PL182898B1/pl not_active IP Right Cessation
- 1995-11-22 NZ NZ298567A patent/NZ298567A/xx unknown
- 1995-11-22 KR KR1019970703470A patent/KR100394548B1/ko not_active IP Right Cessation
- 1995-11-22 AP APAP/P/1997/000998A patent/AP653A/en active
- 1995-11-22 UA UA97063025A patent/UA48154C2/uk unknown
- 1995-11-22 CN CN95197071A patent/CN1171114A/zh active Pending
- 1995-11-22 RU RU97110790/04A patent/RU2176248C2/ru active
- 1995-11-22 PT PT95942879T patent/PT808325E/pt unknown
- 1995-11-22 DK DK95942879T patent/DK0808325T3/da active
- 1995-11-22 GE GEAP19953794A patent/GEP20002033B/en unknown
- 1995-11-22 JP JP8517059A patent/JPH10509458A/ja not_active Ceased
- 1995-11-23 IL IL11610895A patent/IL116108A/en not_active IP Right Cessation
-
1997
- 1997-05-21 NO NO972320A patent/NO308950B1/no unknown
- 1997-05-23 FI FI972202A patent/FI972202A/fi not_active IP Right Cessation
- 1997-05-23 IS IS4488A patent/IS4488A/is unknown
-
2001
- 2001-03-13 GR GR20010400408T patent/GR3035562T3/el not_active IP Right Cessation
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