BRPI0613697A2 - tratamento de distúrbios de sono-vigìlia - Google Patents
tratamento de distúrbios de sono-vigìlia Download PDFInfo
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- BRPI0613697A2 BRPI0613697A2 BRPI0613697-4A BRPI0613697A BRPI0613697A2 BR PI0613697 A2 BRPI0613697 A2 BR PI0613697A2 BR PI0613697 A BRPI0613697 A BR PI0613697A BR PI0613697 A2 BRPI0613697 A2 BR PI0613697A2
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Classifications
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- 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
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/12—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Emergency Medicine (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Anesthesiology (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US68863805P | 2005-06-08 | 2005-06-08 | |
| US60/688,638 | 2005-06-08 | ||
| PCT/US2006/022407 WO2006133393A1 (en) | 2005-06-08 | 2006-06-07 | Treatment of sleep-wake disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0613697A2 true BRPI0613697A2 (pt) | 2011-01-25 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0613697-4A BRPI0613697A2 (pt) | 2005-06-08 | 2006-06-07 | tratamento de distúrbios de sono-vigìlia |
Country Status (17)
| Country | Link |
|---|---|
| US (8) | US8440715B2 (OSRAM) |
| EP (1) | EP1890684B1 (OSRAM) |
| JP (1) | JP5024635B2 (OSRAM) |
| KR (1) | KR101335941B1 (OSRAM) |
| CN (1) | CN101217949B (OSRAM) |
| AU (1) | AU2006254899B2 (OSRAM) |
| BE (1) | BE2020C004I2 (OSRAM) |
| BR (1) | BRPI0613697A2 (OSRAM) |
| CA (1) | CA2611713C (OSRAM) |
| DK (1) | DK1890684T3 (OSRAM) |
| ES (1) | ES2435403T3 (OSRAM) |
| FR (1) | FR20C1014I2 (OSRAM) |
| NL (1) | NL301037I2 (OSRAM) |
| PL (1) | PL1890684T3 (OSRAM) |
| RU (1) | RU2417077C2 (OSRAM) |
| TW (2) | TWI419681B (OSRAM) |
| WO (1) | WO2006133393A1 (OSRAM) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101217949B (zh) | 2005-06-08 | 2012-10-17 | 爱思开生物制药株式会社 | 治疗睡眠-清醒病症 |
| DE602006012670D1 (de) * | 2005-06-22 | 2010-04-15 | Sk Holdings Co Ltd | Behandlung der sexuellen dysfunktion |
| CA2765463C (en) * | 2009-06-22 | 2018-10-09 | Moise A. Khayrallah | Methods for treating or preventing fatigue |
| US8232315B2 (en) * | 2009-06-26 | 2012-07-31 | Sk Biopharmaceuticals Co., Ltd. | Methods for treating drug addiction and improving addiction-related behavior |
| RU2556585C2 (ru) * | 2009-11-06 | 2015-07-10 | Ск Биофармасъютиклс Ко., Лтд. | Способы лечения синдрома дефицита внимания и гиперактивности |
| ES2743153T3 (es) * | 2009-11-06 | 2020-02-18 | Sk Biopharmaceuticals Co Ltd | Métodos para tratar el síndrome de fibromialgia |
| US8623913B2 (en) * | 2010-06-30 | 2014-01-07 | Sk Biopharmaceuticals Co., Ltd. | Methods for treating restless legs syndrome |
| US9610274B2 (en) | 2010-06-30 | 2017-04-04 | Sk Biopharmaceuticals Co., Ltd. | Methods for treating bipolar disorder |
| DK2968208T3 (da) * | 2013-03-13 | 2022-08-22 | Jazz Pharmaceuticals Ireland Ltd | Behandling af kataplexi |
| TW201919605A (zh) | 2013-07-18 | 2019-06-01 | 南韓商愛思開生物製藥股份有限公司 | 肥胖之治療 |
| TWI698415B (zh) | 2014-02-28 | 2020-07-11 | 南韓商愛思開生物製藥股份有限公司 | 胺基羰基胺基甲酸酯化合物 |
| US10888542B2 (en) | 2014-02-28 | 2021-01-12 | Sk Biopharmaceuticals Co., Ltd. | Aminocarbonylcarbamate compounds |
| WO2016061488A1 (en) | 2014-10-17 | 2016-04-21 | Concert Pharmaceuticals, Inc. | Amine reuptake inhibitors |
| JP6466792B2 (ja) * | 2015-07-03 | 2019-02-06 | エスケー バイオファーマスティカルズ カンパニー リミテッド | 注意欠陥／多動性障害（ａｄｈｄ）の治療方法 |
| TWI637765B (zh) * | 2016-05-10 | 2018-10-11 | 台灣共振波研發股份有限公司 | Soothing device for attention deficit hyperactivity disorder |
| US10195151B2 (en) | 2016-09-06 | 2019-02-05 | Jazz Pharmaceuticals International Iii Limited | Formulations of (R)-2-amino-3-phenylpropyl carbamate |
| KR102513800B1 (ko) | 2016-09-06 | 2023-03-24 | 에스케이바이오팜 주식회사 | (r)-2-아미노-3-페닐프로필 카바메이트의 용매화물 폼 |
| MY202185A (en) | 2016-10-06 | 2024-04-15 | Jazz Pharmaceuticals Ireland Ltd | Carbamoyl phenylalaninol compounds and uses therof |
| EP3630072A4 (en) | 2017-06-02 | 2021-03-10 | Jazz Pharmaceuticals Ireland Limited | METHODS AND COMPOSITIONS FOR TREATMENT OF EXCESSIVE Drowsiness |
| WO2019027941A1 (en) * | 2017-07-31 | 2019-02-07 | Jazz Pharmaceuticals International Iii Limited | CARBAMOYL PHENYLALANINOL ANALOGUES AND USES THEREOF |
| US10940133B1 (en) | 2020-03-19 | 2021-03-09 | Jazz Pharmaceuticals Ireland Limited | Methods of providing solriamfetol therapy to subjects with impaired renal function |
| US11033214B1 (en) * | 2020-05-19 | 2021-06-15 | United Arab Emirates University | Wearable eye tracking system |
| KR102390194B1 (ko) * | 2020-08-03 | 2022-04-25 | 셀라이온바이오메드 주식회사 | 페닐알킬 카바메이트 화합물을 포함하는 Kca3.1채널 매개질환 치료용 조성물 |
| AU2023375326A1 (en) * | 2022-11-07 | 2025-05-22 | Axsome Therapeutics | Compositions and methods for treating insomnia |
| EP4626417A1 (en) * | 2022-11-30 | 2025-10-08 | Axsome Therapeutics | Methods and compositions for improving driving performance |
| WO2025006965A1 (en) | 2023-06-29 | 2025-01-02 | Axsome Therapeutics, Inc. | Methods of administering solriamfetol to lactating women |
| WO2025165760A1 (en) * | 2024-01-29 | 2025-08-07 | Axsome Therapeutics, Inc. | Phenylalkylamino carbamates for use in the treatment of attention deficit/hyperactivity disorder |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2939660A1 (de) | 1979-09-29 | 1981-04-16 | Basf Ag, 6700 Ludwigshafen | Neue carbamate, ihre herstellung und diese enthaltende pharmazeutische zubereitungen |
| CZ285829B6 (cs) | 1993-06-10 | 1999-11-17 | Eli Lilly And Company | Použití derivátu tetrahydrobenz [c,d]indolu pro výrobu farmaceutického prostředku vhodného pro ošetřování sexuální dysfunkce |
| KR100197892B1 (ko) | 1994-09-09 | 1999-06-15 | 남창우 | 신규한 페닐알킬아미노 카바메이트 화합물과 그의 제조방법 |
| US5756817C1 (en) * | 1995-02-11 | 2001-04-17 | Sk Corp | O-carbamoyl-phenylananinol compounds their pharmaceutically useful salts and process for preparing the same |
| KR0173862B1 (ko) * | 1995-02-11 | 1999-04-01 | 조규향 | O-카바모일-(d)-페닐알라닌올 화합물과 그의 약제학적으로 유용한 염 및 이들의 제조방법 |
| KR0173863B1 (ko) | 1995-04-10 | 1999-04-01 | 조규향 | 페닐에 치환체가 있는 o-카바모일-페닐알라닌올 화합물과 그의 약제학적으로 유용한 염 및 이들의 제조방법 |
| ES2170878T3 (es) | 1996-10-10 | 2002-08-16 | Sk Corp | Compuestos de o-carbamoil-fenilalaninol y sus sales farmaceuticamente utiles. |
| WO1998017636A1 (en) | 1996-10-22 | 1998-04-30 | Ortho Pharmaceutical Corporation | Phenylalaninol derivatives for the treatment of central nervous system disorders |
| WO2002067921A1 (en) | 2001-02-27 | 2002-09-06 | Ortho-Mcneil Pharmaceutical, Inc. | Carbamate compounds for use in preventing or treating bipolar disorder |
| WO2002067926A1 (en) | 2001-02-27 | 2002-09-06 | Ortho-Mcneil Pharmaceutical, Inc. | Carbamate compounds for use in preventing or treating movement disorders |
| DK1399144T3 (da) | 2001-02-27 | 2006-07-24 | Ortho Mcneil Pharm Inc | Carbamatforbindelser til anvendelse ved forebyggelse eller behandling af angstforstyrrelser |
| US20050080268A1 (en) | 2003-10-08 | 2005-04-14 | Yong-Moon Choi | Process of preparing O-carbamoyl compounds in the presence of active amine group |
| US20050203130A1 (en) | 2003-12-02 | 2005-09-15 | Erik Buntinx | Use of D4 and 5-HT2A antagonists, inverse agonists or partial agonists |
| CN101132787A (zh) | 2004-10-28 | 2008-02-27 | Sk株式会社 | 抑郁的辅助疗法 |
| CN101217949B (zh) | 2005-06-08 | 2012-10-17 | 爱思开生物制药株式会社 | 治疗睡眠-清醒病症 |
| DE602006012670D1 (de) | 2005-06-22 | 2010-04-15 | Sk Holdings Co Ltd | Behandlung der sexuellen dysfunktion |
| JP5094720B2 (ja) | 2005-07-26 | 2012-12-12 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | サブスタンス関連障害を処置する方法 |
| CA2673487A1 (en) | 2006-10-13 | 2008-04-24 | Janssen Pharmaceutica Nv | Phenylalkylamino carbamate compositions |
| CA2765463C (en) | 2009-06-22 | 2018-10-09 | Moise A. Khayrallah | Methods for treating or preventing fatigue |
| US8232315B2 (en) | 2009-06-26 | 2012-07-31 | Sk Biopharmaceuticals Co., Ltd. | Methods for treating drug addiction and improving addiction-related behavior |
| RU2556585C2 (ru) | 2009-11-06 | 2015-07-10 | Ск Биофармасъютиклс Ко., Лтд. | Способы лечения синдрома дефицита внимания и гиперактивности |
| ES2743153T3 (es) | 2009-11-06 | 2020-02-18 | Sk Biopharmaceuticals Co Ltd | Métodos para tratar el síndrome de fibromialgia |
| US9610274B2 (en) | 2010-06-30 | 2017-04-04 | Sk Biopharmaceuticals Co., Ltd. | Methods for treating bipolar disorder |
| US8623913B2 (en) | 2010-06-30 | 2014-01-07 | Sk Biopharmaceuticals Co., Ltd. | Methods for treating restless legs syndrome |
| KR102005483B1 (ko) | 2012-10-19 | 2019-07-31 | 삼성디스플레이 주식회사 | 박막 트랜지스터 기판 및 그의 수리 방법 |
| DK2968208T3 (da) * | 2013-03-13 | 2022-08-22 | Jazz Pharmaceuticals Ireland Ltd | Behandling af kataplexi |
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