CN103153063B - 喹啉衍生物及含有其的melk抑制剂 - Google Patents
喹啉衍生物及含有其的melk抑制剂 Download PDFInfo
- Publication number
- CN103153063B CN103153063B CN201180047405.5A CN201180047405A CN103153063B CN 103153063 B CN103153063 B CN 103153063B CN 201180047405 A CN201180047405 A CN 201180047405A CN 103153063 B CN103153063 B CN 103153063B
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- China
- Prior art keywords
- compound
- quinolin
- hydroxyphenyl
- chloro
- cyclopropyl
- Prior art date
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- 0 *C(C(C=C12)N)C=C1N=CC(*)=C2N(*)* Chemical compound *C(C(C=C12)N)C=C1N=CC(*)=C2N(*)* 0.000 description 44
- CYISMTMRBPPERU-KYZUINATSA-N CC[C@H]1CC[C@H](C)CC1 Chemical compound CC[C@H]1CC[C@H](C)CC1 CYISMTMRBPPERU-KYZUINATSA-N 0.000 description 1
- VHSSQSUNXDUFIH-ZAZKALAHSA-N C[C@H](CC1)[C@@H](C)C1N(C=C)[Ar] Chemical compound C[C@H](CC1)[C@@H](C)C1N(C=C)[Ar] VHSSQSUNXDUFIH-ZAZKALAHSA-N 0.000 description 1
Classifications
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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D215/42—Nitrogen atoms attached in position 4
- C07D215/46—Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
-
- 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
- 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
- C07D401/14—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 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
- C07D409/02—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
- C07D409/06—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 carbon chain containing only aliphatic carbon 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
- C07D409/14—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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- 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
-
- 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
- A61K31/47—Quinolines; Isoquinolines
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D401/10—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 carbon chain containing aromatic 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
- C07D409/02—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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36951910P | 2010-07-30 | 2010-07-30 | |
| US61/369,519 | 2010-07-30 | ||
| PCT/US2011/045792 WO2012016082A1 (en) | 2010-07-30 | 2011-07-28 | Quinoline derivatives and melk inhibitors containing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103153063A CN103153063A (zh) | 2013-06-12 |
| CN103153063B true CN103153063B (zh) | 2016-02-17 |
Family
ID=45530500
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201180047405.5A Active CN103153063B (zh) | 2010-07-30 | 2011-07-28 | 喹啉衍生物及含有其的melk抑制剂 |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US9120749B2 (https=) |
| EP (1) | EP2597955B1 (https=) |
| JP (1) | JP5849303B2 (https=) |
| KR (1) | KR101826382B1 (https=) |
| CN (1) | CN103153063B (https=) |
| AU (1) | AU2011282588B2 (https=) |
| BR (1) | BR112013002182B8 (https=) |
| CA (1) | CA2806332C (https=) |
| DK (1) | DK2597955T3 (https=) |
| ES (1) | ES2565627T3 (https=) |
| IL (1) | IL223871A (https=) |
| MX (1) | MX342879B (https=) |
| RU (1) | RU2582610C2 (https=) |
| SG (2) | SG10201505951VA (https=) |
| TW (1) | TWI532483B (https=) |
| WO (1) | WO2012016082A1 (https=) |
Families Citing this family (59)
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| US20130225524A1 (en) * | 2010-11-05 | 2013-08-29 | Deping Chai | Chemical Compounds |
| WO2013109388A2 (en) * | 2012-01-19 | 2013-07-25 | Oncotherapy Science, Inc. | 1,5-naphthyridine derivatives and melk inhibitors containing the same |
| US9745319B2 (en) | 2013-03-15 | 2017-08-29 | Araxes Pharma Llc | Irreversible covalent inhibitors of the GTPase K-Ras G12C |
| US9227978B2 (en) | 2013-03-15 | 2016-01-05 | Araxes Pharma Llc | Covalent inhibitors of Kras G12C |
| JO3805B1 (ar) | 2013-10-10 | 2021-01-31 | Araxes Pharma Llc | مثبطات كراس جي12سي |
| US10254283B2 (en) | 2013-11-12 | 2019-04-09 | Dana-Farber Cancer Institute, Inc. | Biomarker for MELK activity and methods of using same |
| US9840489B2 (en) | 2013-12-20 | 2017-12-12 | Institute Of Pharmacology And Toxicology Academy Of Military Medical Sciences P.L.A. China | Piperidine carboxamide compound, preparation method, and usage thereof |
| JO3556B1 (ar) | 2014-09-18 | 2020-07-05 | Araxes Pharma Llc | علاجات مدمجة لمعالجة السرطان |
| JP2017528498A (ja) | 2014-09-25 | 2017-09-28 | アラクセス ファーマ エルエルシー | Ｋｒａｓ ｇ１２ｃ変異体タンパク質のインヒビター |
| WO2016049568A1 (en) | 2014-09-25 | 2016-03-31 | Araxes Pharma Llc | Methods and compositions for inhibition of ras |
| NZ732511A (en) * | 2014-12-15 | 2018-11-30 | Univ Michigan Regents | Small molecule inhibitors of egfr and pi3k |
| WO2016141296A1 (en) | 2015-03-04 | 2016-09-09 | Dana-Farber Caner Institute, Inc. | Tricyclic kinase inhibitors of melk and methods of use |
| ES2898765T3 (es) | 2015-04-10 | 2022-03-08 | Araxes Pharma Llc | Compuestos de quinazolina sustituidos y métodos de uso de los mismos |
| US10428064B2 (en) | 2015-04-15 | 2019-10-01 | Araxes Pharma Llc | Fused-tricyclic inhibitors of KRAS and methods of use thereof |
| WO2017015562A1 (en) * | 2015-07-22 | 2017-01-26 | Araxes Pharma Llc | Substituted quinazoline compounds and their use as inhibitors of g12c mutant kras, hras and/or nras proteins |
| CN108026046B (zh) * | 2015-07-22 | 2021-12-21 | 亚瑞克西斯制药公司 | 取代的喹唑啉化合物及其作为g12c突变体kras、hras和/或nras蛋白质的抑制剂的用途 |
| US10144724B2 (en) | 2015-07-22 | 2018-12-04 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use thereof |
| EA033686B1 (ru) * | 2015-08-03 | 2019-11-15 | Bristol Myers Squibb Co | Гетероциклические соединения, применимые в качестве модуляторов tnf-альфа |
| WO2017058728A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| EP3356351A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| EP3356359B1 (en) | 2015-09-28 | 2021-10-20 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| EP3356349A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| EP3356347A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| WO2017058902A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| WO2017058805A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| WO2017070256A2 (en) | 2015-10-19 | 2017-04-27 | Araxes Pharma Llc | Method for screening inhibitors of ras |
| KR20180081596A (ko) | 2015-11-16 | 2018-07-16 | 아락세스 파마 엘엘씨 | 치환된 헤테로사이클릭 그룹을 포함하는 2-치환된 퀴나졸린 화합물 및 이의 사용 방법 |
| US9988357B2 (en) | 2015-12-09 | 2018-06-05 | Araxes Pharma Llc | Methods for preparation of quinazoline derivatives |
| AU2016378579A1 (en) * | 2015-12-22 | 2018-06-14 | Vitae Pharmaceuticals, Inc. | Inhibitors of the menin-MLL interaction |
| WO2017172979A1 (en) | 2016-03-30 | 2017-10-05 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use |
| US10646488B2 (en) | 2016-07-13 | 2020-05-12 | Araxes Pharma Llc | Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof |
| IL264178B2 (en) | 2016-07-14 | 2024-05-01 | Crinetics Pharmaceuticals Inc | Somatostatin modulators and uses thereof |
| RU2756982C2 (ru) | 2016-08-31 | 2021-10-07 | Онкотерапи Сайенс, Инк. | Моноклональное антитело против melk и его использование |
| WO2018064510A1 (en) | 2016-09-29 | 2018-04-05 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| EP3523289A1 (en) | 2016-10-07 | 2019-08-14 | Araxes Pharma LLC | Heterocyclic compounds as inhibitors of ras and methods of use thereof |
| PL3558321T3 (pl) * | 2016-12-23 | 2023-10-23 | Felicitex Therapeutics, Inc. | Pochodne chinolin jako inhibitory kinaz dyrk1a i/lub dyrk1b |
| WO2018140513A1 (en) | 2017-01-26 | 2018-08-02 | Araxes Pharma Llc | 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1yl)prop-2-en-1-one derivatives and similar compounds as kras g12c modulators for treating cancer |
| WO2018140599A1 (en) | 2017-01-26 | 2018-08-02 | Araxes Pharma Llc | Benzothiophene and benzothiazole compounds and methods of use thereof |
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| CN109705037A (zh) * | 2019-01-24 | 2019-05-03 | 广西师范大学 | 4-氨基喹啉-3-甲酸酯衍生物及其制备方法和应用 |
| CN109651355A (zh) * | 2019-01-24 | 2019-04-19 | 广西师范大学 | 3-(2-苯并五元杂环)-4-(3-二甲胺丙氨基)喹啉衍生物及其制备方法和应用 |
| EP3959197A4 (en) * | 2019-04-24 | 2022-10-12 | Children's Medical Center Corporation | PAPD5 INHIBITORS AND METHODS OF USE THEREOF |
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| WO2007139496A1 (en) | 2006-05-30 | 2007-12-06 | Clanotech Ab | Quinoline derivatives acting as tyrosine kinase inhibitors |
| WO2008023841A1 (en) | 2006-08-25 | 2008-02-28 | Oncotherapy Science, Inc. | Breast cancer-associated gene, melk, and its interactions with bcl-g |
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| PE20081354A1 (es) * | 2006-11-30 | 2008-11-14 | Genentech Inc | Compuestos de azaindolilo como inhibidores de mek |
| CN100540551C (zh) | 2007-02-01 | 2009-09-16 | 中国药科大学 | 喹啉衍生物、其制备方法及其医药用途 |
| PE20090717A1 (es) * | 2007-05-18 | 2009-07-18 | Smithkline Beecham Corp | Derivados de quinolina como inhibidores de la pi3 quinasa |
| US20100056524A1 (en) | 2008-04-02 | 2010-03-04 | Mciver Edward Giles | Compound |
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| NZ598220A (en) * | 2009-08-17 | 2014-02-28 | Intellikine Llc | Heterocyclic compounds and uses thereof |
| WO2013109388A2 (en) * | 2012-01-19 | 2013-07-25 | Oncotherapy Science, Inc. | 1,5-naphthyridine derivatives and melk inhibitors containing the same |
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| CA2806332C (en) | 2017-11-14 |
| JP2013532727A (ja) | 2013-08-19 |
| US9120749B2 (en) | 2015-09-01 |
| AU2011282588A1 (en) | 2013-03-21 |
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| ES2565627T3 (es) | 2016-04-06 |
| TWI532483B (zh) | 2016-05-11 |
| BR112013002182A2 (pt) | 2016-05-31 |
| IL223871A (en) | 2016-11-30 |
| BR112013002182B8 (pt) | 2023-02-28 |
| KR20130094312A (ko) | 2013-08-23 |
| EP2597955B1 (en) | 2016-01-20 |
| HK1184331A1 (zh) | 2014-01-24 |
| BR112013002182B1 (pt) | 2022-05-03 |
| US20130217671A1 (en) | 2013-08-22 |
| EP2597955A1 (en) | 2013-06-05 |
| CN103153063A (zh) | 2013-06-12 |
| AU2011282588B2 (en) | 2016-01-07 |
| CA2806332A1 (en) | 2012-02-02 |
| DK2597955T3 (en) | 2016-03-14 |
| TW201208686A (en) | 2012-03-01 |
| MX2013001201A (es) | 2013-04-03 |
| RU2582610C2 (ru) | 2016-04-27 |
| RU2013108865A (ru) | 2014-09-10 |
| SG10201505951VA (en) | 2015-08-28 |
| KR101826382B1 (ko) | 2018-02-06 |
| SG187633A1 (en) | 2013-03-28 |
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