DK2257534T3 - 3-aminoalkyl-1,4-diazepan-2-on-melanocortin-5-receptorantagonister - Google Patents
3-aminoalkyl-1,4-diazepan-2-on-melanocortin-5-receptorantagonisterInfo
- Publication number
- DK2257534T3 DK2257534T3 DK09716155.8T DK09716155T DK2257534T3 DK 2257534 T3 DK2257534 T3 DK 2257534T3 DK 09716155 T DK09716155 T DK 09716155T DK 2257534 T3 DK2257534 T3 DK 2257534T3
- Authority
- DK
- Denmark
- Prior art keywords
- diazepan
- melanocortin
- aminoalkyl
- receptor antagonists
- antagonists
- Prior art date
Links
- 102000030612 Melanocortin 5 receptor Human genes 0.000 title 1
- 108010088565 Melanocortin 5 receptor Proteins 0.000 title 1
- 239000002464 receptor antagonist Substances 0.000 title 1
- 229940044551 receptor antagonist Drugs 0.000 title 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/08—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/008—Preparations for oily skin
-
- 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
- C07C271/20—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 carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
-
- 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
- C07C271/22—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 carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- 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
-
- 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
- C07D403/06—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 only aliphatic carbon atoms
-
- 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
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Birds (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Child & Adolescent Psychology (AREA)
- Hematology (AREA)
- Psychology (AREA)
- Physical Education & Sports Medicine (AREA)
- Obesity (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Diabetes (AREA)
- Molecular Biology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3289408P | 2008-02-29 | 2008-02-29 | |
| US12/391,720 US8008291B2 (en) | 2008-02-29 | 2009-02-24 | 3-aminoalkyl-1,4-diazepan-2-one melanocortin-5 receptor antagonists |
| PCT/AU2009/000230 WO2009105823A1 (en) | 2008-02-29 | 2009-02-27 | 3-aminoalkyl-1,4-diazepan-2-one melanocortin-5 receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2257534T3 true DK2257534T3 (da) | 2014-02-03 |
Family
ID=41015440
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK09716155.8T DK2257534T3 (da) | 2008-02-29 | 2009-02-27 | 3-aminoalkyl-1,4-diazepan-2-on-melanocortin-5-receptorantagonister |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US8008291B2 (da) |
| EP (1) | EP2257534B1 (da) |
| JP (1) | JP5503557B2 (da) |
| KR (1) | KR101620114B1 (da) |
| CN (1) | CN102007105B (da) |
| AU (1) | AU2009219106B2 (da) |
| BR (1) | BRPI0907903B1 (da) |
| CA (1) | CA2716250C (da) |
| DK (1) | DK2257534T3 (da) |
| ES (1) | ES2445456T3 (da) |
| HK (1) | HK1148730A1 (da) |
| IL (1) | IL207700A (da) |
| MX (1) | MX2010009487A (da) |
| NZ (1) | NZ587363A (da) |
| PT (1) | PT2257534E (da) |
| RU (1) | RU2530017C2 (da) |
| WO (1) | WO2009105823A1 (da) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101620115B1 (ko) * | 2008-02-29 | 2016-05-12 | 미메티카 피티와이 리미티드 | Ｍｃ5 수용체의 활성을 조절하는 방법 및 이 수용체와 관련된 상태의 치료 방법 |
| WO2010096853A1 (en) * | 2009-02-27 | 2010-09-02 | Mimetica Pty Ltd | Methods of modulating the activity of the mc1 receptor and treatment of conditions related to this receptor |
| CN109956947A (zh) * | 2017-12-25 | 2019-07-02 | 江苏恒瑞医药股份有限公司 | 一种cns抑制剂的新晶型、制备方法及用途 |
| CN115381955B (zh) * | 2021-05-24 | 2024-05-17 | 中国科学技术大学 | 黑皮质素受体mc5r的用途 |
| KR102703324B1 (ko) * | 2022-11-08 | 2024-09-06 | 국민대학교산학협력단 | 아미노벤즈이미다졸 유도체 및 이의 제조방법 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08502883A (ja) * | 1992-08-21 | 1996-04-02 | ヴァー ファルム アーベー | ヒトメラノサイト刺激ホルモンレセプター |
| US5622860A (en) * | 1994-02-17 | 1997-04-22 | The Regents Of The University Of Michigan | Genes encoding melanocortin receptors |
| EP0804460A1 (en) | 1995-01-20 | 1997-11-05 | Molecumetics, Ltd. | Conformationally constrained reverse-turn library and methods relating thereto |
| US5929237A (en) | 1995-10-27 | 1999-07-27 | Molecumetics Ltd. | Reverse-turn mimetics and methods relating thereto |
| AU7162698A (en) | 1997-04-25 | 1998-11-24 | Regents Of The University Of California, The | Dipeptide surrogates containing asparagine-derived tetrahydropyrimidinones |
| AUPP254898A0 (en) | 1998-03-24 | 1998-04-23 | University Of Queensland, The | Peptide turn mimetics |
| AU742747B2 (en) | 1998-03-24 | 2002-01-10 | Mimetica Pty Ltd | Peptide turn mimetics |
| EP1137757A1 (en) * | 1998-11-09 | 2001-10-04 | Merck & Co., Inc. | Dna molecules encoding the melanocortin 5 receptor protein from rhesus monkey |
| RU2241702C2 (ru) * | 2000-05-25 | 2004-12-10 | Ф.Хоффманн-Ля Рош Аг | Замещенные 1-аминоалкиллактамы, фармацевтическая композиция на их основе и способ их получения |
| EP1425029A4 (en) | 2001-08-10 | 2006-06-07 | Palatin Technologies Inc | PEPTIDOMIMETICS OF BIOLOGICALLY ACTIVE METALLOPEPTIDES |
| US20030110518A1 (en) * | 2001-09-28 | 2003-06-12 | Houseknecht Karen L. | Melanocortin-5 receptor sequences and uses thereof |
| US6916812B2 (en) * | 2001-10-09 | 2005-07-12 | Bristol-Myers Squibb Company | Alpha-aminoamide derivatives as melanocortin agonists |
| RS51530B (en) | 2001-11-08 | 2011-06-30 | Ortho-Mcneil Pharmaceutical Inc. | NEW 1,2,4-THIADIAZOLIUM DERIVATIVES AS MELANOCORTINE RECEPTOR MODULATORS |
| US7319107B2 (en) | 2001-11-08 | 2008-01-15 | Johnson & Johnson Consumer Companies, Inc. | 1,2,4-thiadiazolium derivatives as melanocortin receptor modulators |
| WO2003068738A1 (en) | 2002-02-11 | 2003-08-21 | Neurocrine Biosciences, Inc. | Pyrrole derivatives as ligands of melanocortin receptors |
| AU2004303757B2 (en) * | 2003-06-20 | 2009-07-23 | Amgen Inc. | Piperazine derivatives and methods of use |
| US7281642B2 (en) * | 2004-09-16 | 2007-10-16 | Prime Time Toys, Ltd. | Squirting toy |
| WO2008017852A1 (en) | 2006-08-11 | 2008-02-14 | Palatin Technologies, Inc. | Diamine-containing, tetra- substituted piperazine compounds as melanocortin receptor modulators |
| KR101620115B1 (ko) * | 2008-02-29 | 2016-05-12 | 미메티카 피티와이 리미티드 | Ｍｃ5 수용체의 활성을 조절하는 방법 및 이 수용체와 관련된 상태의 치료 방법 |
-
2009
- 2009-02-24 US US12/391,720 patent/US8008291B2/en active Active
- 2009-02-27 CA CA2716250A patent/CA2716250C/en active Active
- 2009-02-27 MX MX2010009487A patent/MX2010009487A/es active IP Right Grant
- 2009-02-27 BR BRPI0907903-3A patent/BRPI0907903B1/pt not_active IP Right Cessation
- 2009-02-27 EP EP09716155.8A patent/EP2257534B1/en active Active
- 2009-02-27 WO PCT/AU2009/000230 patent/WO2009105823A1/en active Application Filing
- 2009-02-27 DK DK09716155.8T patent/DK2257534T3/da active
- 2009-02-27 NZ NZ587363A patent/NZ587363A/en not_active IP Right Cessation
- 2009-02-27 CN CN200980112982.0A patent/CN102007105B/zh active Active
- 2009-02-27 KR KR1020107021383A patent/KR101620114B1/ko active IP Right Grant
- 2009-02-27 ES ES09716155.8T patent/ES2445456T3/es active Active
- 2009-02-27 JP JP2010547917A patent/JP5503557B2/ja active Active
- 2009-02-27 RU RU2010137034/04A patent/RU2530017C2/ru active
- 2009-02-27 PT PT97161558T patent/PT2257534E/pt unknown
- 2009-02-27 AU AU2009219106A patent/AU2009219106B2/en not_active Ceased
-
2010
- 2010-08-19 IL IL207700A patent/IL207700A/en active IP Right Grant
-
2011
- 2011-03-08 HK HK11102369.6A patent/HK1148730A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| RU2530017C2 (ru) | 2014-10-10 |
| US20090221557A1 (en) | 2009-09-03 |
| US8008291B2 (en) | 2011-08-30 |
| WO2009105823A1 (en) | 2009-09-03 |
| MX2010009487A (es) | 2011-03-02 |
| IL207700A0 (en) | 2010-12-30 |
| CN102007105A (zh) | 2011-04-06 |
| KR20100122102A (ko) | 2010-11-19 |
| BRPI0907903B1 (pt) | 2021-11-09 |
| CA2716250C (en) | 2016-02-16 |
| AU2009219106B2 (en) | 2013-09-26 |
| EP2257534A1 (en) | 2010-12-08 |
| CA2716250A1 (en) | 2009-09-03 |
| EP2257534B1 (en) | 2013-11-06 |
| AU2009219106A1 (en) | 2009-09-03 |
| ES2445456T3 (es) | 2014-03-03 |
| NZ587363A (en) | 2012-06-29 |
| BRPI0907903A2 (pt) | 2020-08-18 |
| JP2011513244A (ja) | 2011-04-28 |
| HK1148730A1 (da) | 2011-09-16 |
| JP5503557B2 (ja) | 2014-05-28 |
| CN102007105B (zh) | 2014-09-03 |
| RU2010137034A (ru) | 2012-04-10 |
| EP2257534A4 (en) | 2011-05-04 |
| IL207700A (en) | 2017-01-31 |
| KR101620114B1 (ko) | 2016-05-12 |
| PT2257534E (pt) | 2014-02-17 |
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