MX347706B - Derivados de triazol y su uso para trastornos neurologicos. - Google Patents
Derivados de triazol y su uso para trastornos neurologicos.Info
- Publication number
- MX347706B MX347706B MX2013004588A MX2013004588A MX347706B MX 347706 B MX347706 B MX 347706B MX 2013004588 A MX2013004588 A MX 2013004588A MX 2013004588 A MX2013004588 A MX 2013004588A MX 347706 B MX347706 B MX 347706B
- Authority
- MX
- Mexico
- Prior art keywords
- neurological disorders
- triazole derivatives
- present
- compounds
- concerned
- Prior art date
Links
- 208000012902 Nervous system disease Diseases 0.000 title 1
- 208000025966 Neurological disease Diseases 0.000 title 1
- 229940042055 systemic antimycotics triazole derivative Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 2
- 239000003814 drug Substances 0.000 abstract 1
- 150000002148 esters Chemical class 0.000 abstract 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 abstract 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- -1 triazole compounds Chemical class 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—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
-
- 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D471/02—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 two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Psychology (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
La presente invención está relacionada con nuevos compuestos de triazol de la fórmula (I) en donde A, X, Y, Z, R1, R2 y R3 son como se describen aquí, así como a las sales y ésteres de los mismos farmacéuticamente aceptables. Los compuestos activos de la presente invención tienen afinidad y selectividad hacia el receptor GABA A a5. Además, la presente invención está relacionada con la manufactura de los compuestos de la fórmula (I), con las composiciones farmacéuticas que los comprenden y con su uso como medicamentos.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10190415 | 2010-11-09 | ||
| PCT/EP2011/069496 WO2012062687A1 (en) | 2010-11-09 | 2011-11-07 | Triazole derivatives and their use for neurological disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| MX2013004588A MX2013004588A (es) | 2013-05-17 |
| MX347706B true MX347706B (es) | 2017-05-09 |
Family
ID=44906177
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2013004588A MX347706B (es) | 2010-11-09 | 2011-11-07 | Derivados de triazol y su uso para trastornos neurologicos. |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US8742097B2 (es) |
| EP (1) | EP2638029B1 (es) |
| JP (1) | JP5918774B2 (es) |
| KR (1) | KR20130115294A (es) |
| CN (1) | CN103221402B (es) |
| BR (1) | BR112013011610A2 (es) |
| CA (1) | CA2812667A1 (es) |
| ES (1) | ES2523892T3 (es) |
| MX (1) | MX347706B (es) |
| RU (1) | RU2581504C2 (es) |
| WO (1) | WO2012062687A1 (es) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014001278A1 (en) | 2012-06-26 | 2014-01-03 | Aniona Aps | A phenyl triazole derivative and its use for modulating the gabaa receptor complex |
| US9206160B2 (en) | 2012-06-26 | 2015-12-08 | Saniona Aps | Phenyl triazole derivative and its use for modulating the GABAA receptor complex |
| AU2013283488A1 (en) * | 2012-06-26 | 2015-01-15 | Saniona Aps | A phenyl triazole derivative and its use for modulating the GABAA receptor complex |
| WO2014001280A1 (en) | 2012-06-26 | 2014-01-03 | Aniona Aps | A phenyl triazole derivative and its use for modulating the gabaa receptor complex |
| WO2014001279A1 (en) | 2012-06-26 | 2014-01-03 | Aniona Aps | A phenyl triazole derivative and its use for modulating the gabaa receptor complex |
| PL3250563T3 (pl) | 2015-01-30 | 2022-05-02 | Neurocrine Biosciences, Inc. | Podstawione triazole i dotyczące ich sposoby |
| AR108838A1 (es) * | 2016-06-21 | 2018-10-03 | Bristol Myers Squibb Co | Ácidos de carbamoiloximetil triazol ciclohexilo como antagonistas de lpa |
| US10513515B2 (en) | 2017-08-25 | 2019-12-24 | Biotheryx, Inc. | Ether compounds and uses thereof |
| US10662172B2 (en) | 2017-12-19 | 2020-05-26 | Bristol-Myers Squibb Company | Triazole N-linked carbamoyl cyclohexyl acids as LPA antagonists |
| BR102019014802A2 (pt) * | 2018-07-20 | 2020-02-04 | Boehringer Ingelheim Int | difluorometil-fenil triazóis |
| CA3106239A1 (en) | 2018-07-27 | 2020-01-30 | Biotheryx, Inc. | Bifunctional compounds as cdk modulators |
| HU231223B1 (hu) * | 2018-09-28 | 2022-01-28 | Richter Gedeon Nyrt. | GABAA A5 receptor modulátor hatású biciklusos vegyületek |
| WO2021191837A1 (en) | 2020-03-26 | 2021-09-30 | Richter Gedeon Nyrt. | 1,3-dihydro-2h-pyrrolo[3,4-c]pyridine derivatives as gabaa α5 receptor modulators |
| TWI901650B (zh) * | 2020-03-26 | 2025-10-21 | 匈牙利商羅特格登公司 | 啶及吡啶并〔３，４－ｃ〕嗒衍生物 |
| EP4143329A4 (en) | 2020-04-28 | 2024-10-16 | Anwita Biosciences, Inc. | Interleukin-2 polypeptides and fusion proteins thereof, and their pharmaceutical compositions and therapeutic applications |
| CN115461337A (zh) * | 2020-05-13 | 2022-12-09 | 豪夫迈·罗氏有限公司 | 作为GABA A α5 PAM的新型三唑基衍生物 |
| EP3992188A1 (en) * | 2020-10-29 | 2022-05-04 | Boehringer Ingelheim International GmbH | Difluoromethyl-pyridin-2-yl triazoles |
| JP7802256B2 (ja) * | 2020-08-05 | 2026-01-20 | サニオナ アクティーゼルスカブ | ジフルオロメチル－ピリジン－２－イルトリアゾール |
| KR20240005848A (ko) | 2021-05-05 | 2024-01-12 | 유니버시티 칼리지 카디프 컨설턴츠 리미티드 | 인지 장애의 치료에 유용한 헤테로아릴 화합물 |
| KR20240109975A (ko) * | 2021-08-12 | 2024-07-12 | 상하이 에스아이엠알 바이오테크놀로지 컴퍼니 리미티드 | 치환된 트리아졸 유도체, 이의 제조 방법, 이의 약제학적 조성물, 및 이의 용도 |
| HU231691B1 (hu) | 2021-09-29 | 2025-10-28 | Richter Gedeon Nyrt | GABAA ALFA5 receptor modulátor hatású biciklusos aminszármazékok |
| CN116462664B (zh) * | 2022-03-08 | 2025-07-01 | 上海赛默罗生物科技有限公司 | 吡唑环类化合物、其制备方法、组合物及应用 |
| CN114656472B (zh) * | 2022-04-27 | 2023-07-04 | 成都施贝康生物医药科技有限公司 | 吡唑并嘧啶类化合物、异构体或盐及其制备方法和用途 |
| CN114656473B (zh) * | 2022-04-27 | 2023-09-29 | 成都施贝康生物医药科技有限公司 | 吡咯并嘧啶类化合物、异构体或盐及其制备方法和用途 |
| EP4553080A1 (en) | 2023-11-07 | 2025-05-14 | Ustav Organicke Chemie a Biochemie AV CR, v.v.i. | Nucleoside derivatives as antiviral agents against coronaviruses |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1237793B (it) | 1989-12-21 | 1993-06-17 | Zambon Spa | Composti attivi come inibitori dell'enzima hmg-coa reduttasi |
| TW200533346A (en) * | 2004-03-18 | 2005-10-16 | Hoffmann La Roche | Novel ether derivatives, their manufacture and use as pharmaceutical agents |
| DE602007005256D1 (de) * | 2006-05-24 | 2010-04-22 | Lilly Co Eli | Verbindungen und verfahren zur modulierung von fx-rezeptoren |
| JP2011515359A (ja) * | 2008-03-18 | 2011-05-19 | グラクソ グループ リミテッド | 治療用トリアゾールアミド誘導体 |
| EA019755B1 (ru) | 2008-06-19 | 2014-06-30 | Такеда Фармасьютикал Компани Лимитед | Гетероциклическое соединение и его применение |
-
2011
- 2011-11-02 US US13/287,149 patent/US8742097B2/en active Active
- 2011-11-07 BR BR112013011610A patent/BR112013011610A2/pt not_active IP Right Cessation
- 2011-11-07 KR KR1020137014615A patent/KR20130115294A/ko not_active Ceased
- 2011-11-07 WO PCT/EP2011/069496 patent/WO2012062687A1/en not_active Ceased
- 2011-11-07 ES ES11778911.5T patent/ES2523892T3/es active Active
- 2011-11-07 JP JP2013538143A patent/JP5918774B2/ja not_active Expired - Fee Related
- 2011-11-07 MX MX2013004588A patent/MX347706B/es active IP Right Grant
- 2011-11-07 CN CN201180053924.2A patent/CN103221402B/zh not_active Expired - Fee Related
- 2011-11-07 CA CA2812667A patent/CA2812667A1/en not_active Abandoned
- 2011-11-07 RU RU2013125337/04A patent/RU2581504C2/ru not_active IP Right Cessation
- 2011-11-07 EP EP11778911.5A patent/EP2638029B1/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| ES2523892T3 (es) | 2014-12-02 |
| BR112013011610A2 (pt) | 2016-08-09 |
| WO2012062687A1 (en) | 2012-05-18 |
| HK1182704A1 (en) | 2013-12-06 |
| EP2638029A1 (en) | 2013-09-18 |
| CA2812667A1 (en) | 2012-05-18 |
| US8742097B2 (en) | 2014-06-03 |
| CN103221402A (zh) | 2013-07-24 |
| KR20130115294A (ko) | 2013-10-21 |
| RU2581504C2 (ru) | 2016-04-20 |
| JP2013543852A (ja) | 2013-12-09 |
| RU2013125337A (ru) | 2014-12-20 |
| MX2013004588A (es) | 2013-05-17 |
| CN103221402B (zh) | 2015-06-17 |
| EP2638029B1 (en) | 2014-09-24 |
| JP5918774B2 (ja) | 2016-05-18 |
| US20120115844A1 (en) | 2012-05-10 |
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