CN102549007B - 3α-羟基,3β-甲基-5α-孕烷-20-酮(加奈索酮)的制备方法 - Google Patents

3α-羟基,3β-甲基-5α-孕烷-20-酮(加奈索酮)的制备方法 Download PDF

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Publication number
CN102549007B
CN102549007B CN201080035660.3A CN201080035660A CN102549007B CN 102549007 B CN102549007 B CN 102549007B CN 201080035660 A CN201080035660 A CN 201080035660A CN 102549007 B CN102549007 B CN 102549007B
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China
Prior art keywords
ganaxolone
metallic
organo
alpha
methylating reagent
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English (en)
Chinese (zh)
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CN102549007A (zh
Inventor
肯尼思·肖
艾伦·哈奇森
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Immedica Pharma US Inc
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Marinus Pharmaceuticals Inc
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    • 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
    • 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
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • 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
    • 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
    • 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
    • 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
    • C07J7/004—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 substituted in position 17 alfa
    • C07J7/0045—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 substituted in position 17 alfa not substituted in position 16
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Steroid Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
CN201080035660.3A 2009-08-13 2010-08-11 3α-羟基,3β-甲基-5α-孕烷-20-酮(加奈索酮)的制备方法 Active CN102549007B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US23355309P 2009-08-13 2009-08-13
US61/233,553 2009-08-13
PCT/US2010/045176 WO2011019821A2 (en) 2009-08-13 2010-08-11 METHOD FOR MAKING 3α-HYDROXY, 3β- METHYL-5α-PREGNAN-20-ONE (GANAXOLONE)

Publications (2)

Publication Number Publication Date
CN102549007A CN102549007A (zh) 2012-07-04
CN102549007B true CN102549007B (zh) 2015-03-18

Family

ID=43586809

Family Applications (1)

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CN201080035660.3A Active CN102549007B (zh) 2009-08-13 2010-08-11 3α-羟基,3β-甲基-5α-孕烷-20-酮(加奈索酮)的制备方法

Country Status (14)

Country Link
US (1) US8362286B2 (https=)
EP (1) EP2464653B1 (https=)
JP (1) JP5745517B2 (https=)
KR (1) KR101778603B1 (https=)
CN (1) CN102549007B (https=)
AU (1) AU2010282570B2 (https=)
BR (1) BR112012003085B1 (https=)
CA (1) CA2769820C (https=)
EA (1) EA024269B1 (https=)
ES (1) ES2524724T3 (https=)
IL (1) IL217857A (https=)
MX (1) MX2012001728A (https=)
NZ (1) NZ597940A (https=)
WO (1) WO2011019821A2 (https=)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101583620B (zh) 2005-11-28 2016-08-17 马里纳斯医药公司 加奈索酮组合物及其制备和使用方法
US9629853B2 (en) 2014-05-21 2017-04-25 Wisconsin Alumni Research Foundation Uses of ganaxolone
CZ305837B6 (cs) * 2015-02-25 2016-03-30 Vysoká škola chemicko - technologická v Praze (3α,5β,20S)-3-Nitrooxy-pregnan-20-karboxylová kyselina
EA036155B1 (ru) 2015-10-16 2020-10-06 Маринус Фармасьютикалс, Инк. Инъекционные составы нейростероида, содержащие наночастицы
CN106366149B (zh) * 2016-08-09 2018-01-23 南京臣功制药股份有限公司 一种醋酸甲羟孕酮分散片的有关物质及其分析检测方法
CN106279326A (zh) * 2016-08-09 2017-01-04 南京臣功制药股份有限公司 一种醋酸甲羟孕酮胶囊的有关物质及其分析检测方法
EP4233861A3 (en) 2016-08-11 2023-10-11 Ovid Therapeutics, Inc. Compositions for treatment of essential tremor
US10391105B2 (en) 2016-09-09 2019-08-27 Marinus Pharmaceuticals Inc. Methods of treating certain depressive disorders and delirium tremens
IT201800009683A1 (it) * 2018-10-22 2020-04-22 Ind Chimica Srl Processo per la preparazione di 3α-idrossi-5α-pregnan-20-one (brexanolone)
US11266662B2 (en) 2018-12-07 2022-03-08 Marinus Pharmaceuticals, Inc. Ganaxolone for use in prophylaxis and treatment of postpartum depression
CN114728012A (zh) 2019-08-05 2022-07-08 马瑞纳斯制药公司 用于治疗癫痫持续状态的加奈索酮
JP7780431B2 (ja) 2019-12-06 2025-12-04 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
IT202000021316A1 (it) * 2020-09-09 2022-03-09 Ind Chimica Srl PROCESSO PER LA PREPARAZIONE DI (3α,5α)-3-IDROSSI-3-METIL-PREGNAN-20-ONE (GANAXOLONE)

Citations (3)

* Cited by examiner, † Cited by third party
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
US6117994A (en) * 1994-06-02 2000-09-12 Hoechst Marion Roussel Intermediates for 16β-methyl steroids
WO2007062266A2 (en) * 2005-11-28 2007-05-31 Marinus Pharmaceuticals Ganaxolone formulations and methods for the making and use thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
US5319115A (en) 1987-08-25 1994-06-07 Cocensys Inc. Method for making 3α-hydroxy, 3β-substituted-pregnanes
AU698834B2 (en) * 1993-05-24 1998-11-12 Purdue Pharma Ltd. Methods and compositions for inducing sleep
FI972202L (fi) * 1994-11-23 1997-07-17 Cocensys Inc Androstaanit ja pregnaanit GABA-reseptoreiden allosteeriseen muunteluun
US20060009432A1 (en) * 2004-07-09 2006-01-12 Roger Whiting Use of neurosteroids to treat neuropathic pain

Patent Citations (3)

* Cited by examiner, † Cited by third party
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
US6117994A (en) * 1994-06-02 2000-09-12 Hoechst Marion Roussel Intermediates for 16β-methyl steroids
WO2007062266A2 (en) * 2005-11-28 2007-05-31 Marinus Pharmaceuticals Ganaxolone formulations and methods for the making and use thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Substituted 3β-Phenylethynyl Derivatives of 3α-Hydroxy-5α-pregnan-20-one: Remarkably Potent Neuroactive Steroid Modulators of γ-Aminobutyric Acida Receptors;JON E.KAWKINSON et al;《THE JOURANL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》;19981231;第287卷(第1期);第198-207页 *
Synthesis and in Vitro Activity of 3β-Substituted-3α-hydroxypregnan-20-ones: Allosteric Modulators of the GABAa Receptor;Derk J.Hogenkamp et al;《J.Med.Chem.》;19971231;第40卷(第1期);第61-72页 *
加那索酮的合成;何明华等;《中国新药杂志》;20051231;第14卷(第8期);第1025-1028页 *

Also Published As

Publication number Publication date
AU2010282570B2 (en) 2014-04-24
KR101778603B1 (ko) 2017-09-14
EA024269B1 (ru) 2016-09-30
EP2464653A4 (en) 2013-01-16
JP5745517B2 (ja) 2015-07-08
EA201270241A1 (ru) 2013-09-30
CA2769820C (en) 2017-06-27
ES2524724T3 (es) 2014-12-11
AU2010282570A1 (en) 2012-02-23
HK1171761A1 (en) 2013-04-05
CA2769820A1 (en) 2011-02-17
IL217857A0 (en) 2012-03-29
IL217857A (en) 2016-03-31
JP2013501803A (ja) 2013-01-17
WO2011019821A3 (en) 2011-06-16
BR112012003085A2 (pt) 2020-12-01
CN102549007A (zh) 2012-07-04
EP2464653A2 (en) 2012-06-20
NZ597940A (en) 2013-03-28
BR112012003085B1 (pt) 2021-06-01
US8362286B2 (en) 2013-01-29
KR20120084715A (ko) 2012-07-30
US20110040112A1 (en) 2011-02-17
WO2011019821A2 (en) 2011-02-17
MX2012001728A (es) 2012-06-01
EP2464653B1 (en) 2014-10-22

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