JP5727945B2 - Ｋｃｎｑ２／３モジュレータとしての置換された３−アミノ−２−メルカプトキノリン - Google Patents
Ｋｃｎｑ２／３モジュレータとしての置換された３−アミノ−２−メルカプトキノリン Download PDFInfo
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- JP5727945B2 JP5727945B2 JP2011553339A JP2011553339A JP5727945B2 JP 5727945 B2 JP5727945 B2 JP 5727945B2 JP 2011553339 A JP2011553339 A JP 2011553339A JP 2011553339 A JP2011553339 A JP 2011553339A JP 5727945 B2 JP5727945 B2 JP 5727945B2
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- Prior art keywords
- alkyl
- quinolin
- group
- substituted
- heteroalkyl
- Prior art date
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- WPFIJUWKLJCQOO-UHFFFAOYSA-N 3-amino-1h-quinoline-2-thione Chemical class C1=CC=C2NC(=S)C(N)=CC2=C1 WPFIJUWKLJCQOO-UHFFFAOYSA-N 0.000 title claims description 17
- 108010006746 KCNQ2 Potassium Channel Proteins 0.000 title description 17
- 102000005453 KCNQ2 Potassium Channel Human genes 0.000 title description 17
- 125000003118 aryl group Chemical group 0.000 claims description 70
- 125000001072 heteroaryl group Chemical group 0.000 claims description 67
- 229920006395 saturated elastomer Polymers 0.000 claims description 52
- -1 2- (phenylthio) ethyl Chemical group 0.000 claims description 45
- 208000002193 Pain Diseases 0.000 claims description 36
- 150000001875 compounds Chemical class 0.000 claims description 35
- 125000005842 heteroatom Chemical group 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 25
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- 125000004404 heteroalkyl group Chemical group 0.000 claims description 24
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- 206010015037 epilepsy Diseases 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- KXZSVYHFYHTNBI-UHFFFAOYSA-N 1h-quinoline-2-thione Chemical group C1=CC=CC2=NC(S)=CC=C21 KXZSVYHFYHTNBI-UHFFFAOYSA-N 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
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- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
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- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 3
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- NBQOMSWDPMGLDV-UHFFFAOYSA-N 3-cyclopentyl-n-(2-ethylsulfanylquinolin-3-yl)propanamide Chemical compound CCSC1=NC2=CC=CC=C2C=C1NC(=O)CCC1CCCC1 NBQOMSWDPMGLDV-UHFFFAOYSA-N 0.000 claims description 2
- LIJKURWCGLPYFP-UHFFFAOYSA-N 3-cyclopentyl-n-[2-ethylsulfanyl-7-(trifluoromethyl)quinolin-3-yl]propanamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C=C1NC(=O)CCC1CCCC1 LIJKURWCGLPYFP-UHFFFAOYSA-N 0.000 claims description 2
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- KGKPFBQUXFOPTK-UHFFFAOYSA-N n-(2-ethylsulfanylquinolin-3-yl)-3,3-dimethylbutanamide Chemical compound C1=CC=C2C=C(NC(=O)CC(C)(C)C)C(SCC)=NC2=C1 KGKPFBQUXFOPTK-UHFFFAOYSA-N 0.000 claims description 2
- IWQRREJPCILBIR-UHFFFAOYSA-N n-[2-ethylsulfanyl-4-methyl-7-(trifluoromethyl)quinolin-3-yl]-2-thiophen-2-ylacetamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1NC(=O)CC1=CC=CS1 IWQRREJPCILBIR-UHFFFAOYSA-N 0.000 claims description 2
- LGRCIDLJCYQTGX-UHFFFAOYSA-N n-[2-ethylsulfanyl-7-(trifluoromethyl)quinolin-3-yl]-3,3-dimethylbutanamide Chemical compound FC(F)(F)C1=CC=C2C=C(NC(=O)CC(C)(C)C)C(SCC)=NC2=C1 LGRCIDLJCYQTGX-UHFFFAOYSA-N 0.000 claims description 2
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- BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 claims 2
- HDBQZGJWHMCXIL-UHFFFAOYSA-N 3,7-dihydropurine-2-thione Chemical compound SC1=NC=C2NC=NC2=N1 HDBQZGJWHMCXIL-UHFFFAOYSA-N 0.000 claims 1
- 238000004132 cross linking Methods 0.000 claims 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N purine-6-thione Natural products S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
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- 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
- A61K31/47—Quinolines; Isoquinolines
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- A—HUMAN NECESSITIES
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
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- Organic Chemistry (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
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- Psychiatry (AREA)
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- Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Addiction (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09003431 | 2009-03-10 | ||
| EP09003431.5 | 2009-03-10 | ||
| PCT/EP2010/001449 WO2010102779A1 (de) | 2009-03-10 | 2010-03-09 | Substituierte 3-amino-2-mercaptochinoline als kcnq2/3 modulatoren |
Publications (3)
| Publication Number | Publication Date |
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| JP2012521966A JP2012521966A (ja) | 2012-09-20 |
| JP2012521966A5 JP2012521966A5 (https=) | 2014-10-16 |
| JP5727945B2 true JP5727945B2 (ja) | 2015-06-03 |
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| JP2011553339A Expired - Fee Related JP5727945B2 (ja) | 2009-03-10 | 2010-03-09 | Ｋｃｎｑ２／３モジュレータとしての置換された３−アミノ−２−メルカプトキノリン |
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| EP (1) | EP2406228B1 (https=) |
| JP (1) | JP5727945B2 (https=) |
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| CN (1) | CN102341374A (https=) |
| AR (1) | AR075730A1 (https=) |
| AU (1) | AU2010223556B2 (https=) |
| BR (1) | BRPI1009519A2 (https=) |
| CA (1) | CA2754943A1 (https=) |
| CL (1) | CL2011002160A1 (https=) |
| CO (1) | CO6410291A2 (https=) |
| EC (1) | ECSP11011346A (https=) |
| ES (1) | ES2436365T3 (https=) |
| IL (1) | IL214944A0 (https=) |
| MX (1) | MX2011009338A (https=) |
| NZ (1) | NZ595569A (https=) |
| PE (1) | PE20120535A1 (https=) |
| PL (1) | PL2406228T3 (https=) |
| RU (1) | RU2011140701A (https=) |
| TW (1) | TWI504395B (https=) |
| WO (1) | WO2010102779A1 (https=) |
| ZA (1) | ZA201107370B (https=) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2754934A1 (en) * | 2009-03-10 | 2010-09-16 | Gruenenthal Gmbh | Substituted 3-aminoisoxazolopyridines as kcnq2/3 modulators |
| TWI461197B (zh) * | 2009-03-12 | 2014-11-21 | 2-mercaptoquinoline-3-carboxamide as a KCNQ2 / 3 modifier | |
| TW201038565A (en) | 2009-03-12 | 2010-11-01 | Gruenenthal Gmbh | Substituted 2-mercapto-3-aminopyridines as KCNQ2/3 modulators |
| TWI475020B (zh) | 2009-03-12 | 2015-03-01 | The substituted nicotine amide as a KCNQ2 / 3 modifier | |
| MX342459B (es) | 2010-08-27 | 2016-09-29 | Grünenthal Gmbh * | 2-oxo- y 2-tioxo-dihidroquinolin-3-carboxamidas sustituidas, como moduladores de kcnq2/3. |
| CA2805932A1 (en) | 2010-08-27 | 2012-03-01 | Gruenenthal Gmbh | Substituted 2-amino-quinoline-3-carboxamides as kcnq2/3 modulators |
| RU2595894C2 (ru) | 2010-08-27 | 2016-08-27 | Грюненталь Гмбх | Замещенные 2-окси-хинолин-3-карбоксамиды в качестве модуляторов kcnq2/3 |
| CA2807886A1 (en) | 2010-09-01 | 2012-03-08 | Gruenenthal Gmbh | Substituted 1-oxo-dihydroisoquinoline-3-carboxamides as kcnq2/3 modulators |
| DE102018212006B3 (de) * | 2018-07-18 | 2019-10-31 | Universität Greifswald | Thioether als Modulatoren von Kv7.2/Kv7.3-Kanälen |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2706977A1 (de) | 1977-02-18 | 1978-08-24 | Hoechst Ag | Benzoesaeuren und deren derivate sowie verfahren zu ihrer herstellung |
| FR2532939A1 (fr) | 1982-09-13 | 1984-03-16 | Roussel Uclaf | Nouveaux derives de l'acide 4-hydroxy 3-quinoleine carboxylique substitues en 2, leur preparation, leur application comme medicament, les compositions les renfermant et les nouveaux intermediaires obtenus |
| DE4032147A1 (de) | 1990-10-10 | 1992-04-16 | Bayer Ag | Verwendung von substituierten 2-mercaptonicotinsaeurederivaten zur bekaempfung von endoparasiten, neue substituierte 2-mercaptonicotinsaeurederivate und verfahren zu ihrer herstellung |
| US5583147A (en) * | 1994-03-23 | 1996-12-10 | The Dupont Merck Pharmaceutical Company | Amides for the treatment of atherosclerosis |
| EP0716077A1 (de) | 1994-12-08 | 1996-06-12 | Ciba-Geigy Ag | Aromatisch substituierte Omega-Aminoalkansäureamide und Alkansäurediamide und ihre Verwendung als Renininhibitoren |
| WO1996026925A1 (en) | 1995-03-01 | 1996-09-06 | Banyu Pharmaceutical Co., Ltd. | Arylthioacetamide derivatives |
| AU742452B2 (en) * | 1997-08-28 | 2002-01-03 | Bristol-Myers Squibb Company | 4-aryl-3-aminoquinoline-2-one derivatives as potassium channel modulators |
| DE19738616A1 (de) | 1997-09-04 | 1999-03-11 | Clariant Gmbh | 4-Hydroxychinolin-3-carbonsäure-Derivate als Lichtschutzmittel |
| WO2000042026A1 (en) | 1999-01-15 | 2000-07-20 | Novo Nordisk A/S | Non-peptide glp-1 agonists |
| EP1200086A4 (en) | 1999-08-04 | 2009-05-27 | Icagen Inc | THERAPEUTIC OR PROPHYLACTIC METHODS OF PAIN AND ANXIETY |
| ATE380176T1 (de) | 1999-08-04 | 2007-12-15 | Icagen Inc | Benzanilide als öffner des kaliumkanals |
| CA2438868A1 (en) | 2001-02-20 | 2002-09-19 | Valentin K. Gribkoff | Modulators of kcnq potassium channels and use thereof in treating migraine and mechanistically related diseases |
| CZ20032233A3 (cs) | 2001-02-20 | 2004-12-15 | Bristol-Myers Squibb Company | Derivát 2,4-disubstituovaného pyrimidin-5-karboxamidu jako modulátor draslíkového kanálku KCNQ |
| US6593349B2 (en) | 2001-03-19 | 2003-07-15 | Icagen, Inc. | Bisarylamines as potassium channel openers |
| EP1372654A4 (en) | 2001-04-06 | 2007-10-03 | Smithkline Beecham Corp | QUINOLINE INHIBITORS OF HYAK1 AND HYAK3 KINASES |
| AU2003272552A1 (en) | 2002-09-17 | 2004-04-08 | Pharmacia Corporation | Aromatic liver x-receptor modulators |
| ATE488231T1 (de) | 2002-12-23 | 2010-12-15 | Icagen Inc | Quinazolinone als kaliumkanalmodulatoren |
| EP1449841A1 (en) | 2003-02-19 | 2004-08-25 | Bayer CropScience SA | New fungicidal compounds |
| MXPA06004005A (es) | 2003-10-08 | 2006-06-28 | Vertex Pharma | Moduladores de transportadores con casete de union con atp. |
| JP4054369B2 (ja) | 2004-05-04 | 2008-02-27 | ファイザー株式会社 | オルト置換アリールまたはヘテロアリールアミド化合物 |
| WO2006051311A1 (en) | 2004-11-12 | 2006-05-18 | Galapagos Nv | Nitrogen heteroaromatic compounds which bind to the active site of protein kinase enzymes |
| EP1861394A1 (en) | 2005-03-03 | 2007-12-05 | H.Lundbeck A/S | Substituted pyridine derivatives |
| DE102005038947A1 (de) | 2005-05-18 | 2006-11-30 | Grünenthal GmbH | Substituierte Benzo[d]isoxazol-3-yl-amin-Verbindungen und deren Verwendung in Arzneimitteln |
| EP1912946B1 (en) | 2005-07-20 | 2009-05-27 | Eli Lilly And Company | Pyridine derivatives as dipeptedyl peptidase inhibitors |
| CN101277939A (zh) | 2005-09-09 | 2008-10-01 | 布里斯托尔-迈尔斯斯奎布公司 | 无环ikur抑制剂 |
| WO2007057447A1 (en) * | 2005-11-18 | 2007-05-24 | Neurosearch A/S | Novel quinazoline derivatives and their medical use |
| CA2658190C (en) | 2006-07-20 | 2013-01-29 | Amgen Inc. | Di-amino-substituted heterocyclic compounds and methods of use |
| AU2007275653B2 (en) | 2006-07-20 | 2010-12-23 | Amgen Inc. | Benzo(d) isoxazole derivatives as c-kit tyrosine kinase inhibitors for the treatment of disorders associated with the over production of histamine |
| US20100022589A1 (en) | 2006-07-27 | 2010-01-28 | Mccoull William | Pyridine-3-carboxamide compounds and their use for inhibiting 11-beta-hydroxysteroid dehydrogenase |
| DE102006049452A1 (de) | 2006-10-17 | 2008-05-08 | Grünenthal GmbH | Substituierte Tetrahydropyrolopiperazin-Verbindungen und deren Verwendung in Arzneimitteln |
| US8563566B2 (en) | 2007-08-01 | 2013-10-22 | Valeant Pharmaceuticals International | Naphthyridine derivatives as potassium channel modulators |
| JP5341084B2 (ja) | 2007-08-03 | 2013-11-13 | エフ．ホフマン−ラ ロシュ アーゲー | Ｔａａｒ１リガンドとしてのピリジンカルボキシアミド及びベンズアミド誘導体 |
| EP2215065B1 (en) | 2007-10-19 | 2012-07-11 | Boehringer Ingelheim International GmbH | Ccr10 antagonists |
| CA2754934A1 (en) | 2009-03-10 | 2010-09-16 | Gruenenthal Gmbh | Substituted 3-aminoisoxazolopyridines as kcnq2/3 modulators |
| TW201038565A (en) | 2009-03-12 | 2010-11-01 | Gruenenthal Gmbh | Substituted 2-mercapto-3-aminopyridines as KCNQ2/3 modulators |
| TWI475020B (zh) | 2009-03-12 | 2015-03-01 | The substituted nicotine amide as a KCNQ2 / 3 modifier | |
| TWI461197B (zh) * | 2009-03-12 | 2014-11-21 | 2-mercaptoquinoline-3-carboxamide as a KCNQ2 / 3 modifier |
-
2010
- 2010-03-03 TW TW099106075A patent/TWI504395B/zh not_active IP Right Cessation
- 2010-03-09 AU AU2010223556A patent/AU2010223556B2/en not_active Ceased
- 2010-03-09 PL PL10708503T patent/PL2406228T3/pl unknown
- 2010-03-09 CA CA2754943A patent/CA2754943A1/en not_active Abandoned
- 2010-03-09 PE PE2011001564A patent/PE20120535A1/es not_active Application Discontinuation
- 2010-03-09 NZ NZ595569A patent/NZ595569A/xx not_active IP Right Cessation
- 2010-03-09 RU RU2011140701/04A patent/RU2011140701A/ru not_active Application Discontinuation
- 2010-03-09 BR BRPI1009519A patent/BRPI1009519A2/pt not_active IP Right Cessation
- 2010-03-09 WO PCT/EP2010/001449 patent/WO2010102779A1/de not_active Ceased
- 2010-03-09 ES ES10708503T patent/ES2436365T3/es active Active
- 2010-03-09 JP JP2011553339A patent/JP5727945B2/ja not_active Expired - Fee Related
- 2010-03-09 EP EP10708503.7A patent/EP2406228B1/de not_active Not-in-force
- 2010-03-09 CN CN2010800109786A patent/CN102341374A/zh active Pending
- 2010-03-09 KR KR1020117023698A patent/KR20110130461A/ko not_active Withdrawn
- 2010-03-09 MX MX2011009338A patent/MX2011009338A/es active IP Right Grant
- 2010-03-10 US US12/720,770 patent/US8207342B2/en not_active Expired - Fee Related
- 2010-03-10 AR ARP100100719A patent/AR075730A1/es not_active Application Discontinuation
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2011
- 2011-08-12 CO CO11102966A patent/CO6410291A2/es not_active Application Discontinuation
- 2011-09-02 CL CL2011002160A patent/CL2011002160A1/es unknown
- 2011-09-04 IL IL214944A patent/IL214944A0/en unknown
- 2011-09-23 EC EC2011011346A patent/ECSP11011346A/es unknown
- 2011-10-07 ZA ZA2011/07370A patent/ZA201107370B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TWI504395B (zh) | 2015-10-21 |
| MX2011009338A (es) | 2011-09-27 |
| RU2011140701A (ru) | 2013-04-20 |
| JP2012521966A (ja) | 2012-09-20 |
| ZA201107370B (en) | 2012-07-25 |
| AU2010223556B2 (en) | 2015-01-29 |
| EP2406228A1 (de) | 2012-01-18 |
| IL214944A0 (en) | 2011-11-30 |
| CL2011002160A1 (es) | 2012-08-17 |
| ES2436365T3 (es) | 2013-12-30 |
| KR20110130461A (ko) | 2011-12-05 |
| US20100234421A1 (en) | 2010-09-16 |
| PE20120535A1 (es) | 2012-05-09 |
| US8207342B2 (en) | 2012-06-26 |
| BRPI1009519A2 (pt) | 2016-03-15 |
| AR075730A1 (es) | 2011-04-20 |
| AU2010223556A1 (en) | 2011-11-03 |
| CO6410291A2 (es) | 2012-03-30 |
| TW201036610A (en) | 2010-10-16 |
| EP2406228B1 (de) | 2013-09-18 |
| WO2010102779A1 (de) | 2010-09-16 |
| CA2754943A1 (en) | 2010-09-16 |
| PL2406228T3 (pl) | 2014-02-28 |
| CN102341374A (zh) | 2012-02-01 |
| ECSP11011346A (es) | 2011-10-31 |
| NZ595569A (en) | 2012-11-30 |
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