KR20120087916A - 마크로시클릭 인테그라제 억제제 - Google Patents
마크로시클릭 인테그라제 억제제 Download PDFInfo
- Publication number
- KR20120087916A KR20120087916A KR1020127009345A KR20127009345A KR20120087916A KR 20120087916 A KR20120087916 A KR 20120087916A KR 1020127009345 A KR1020127009345 A KR 1020127009345A KR 20127009345 A KR20127009345 A KR 20127009345A KR 20120087916 A KR20120087916 A KR 20120087916A
- Authority
- KR
- South Korea
- Prior art keywords
- mmol
- formula
- naphthyridine
- methyl
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 0 CC(C)(C)OC(NCc(cc1)c(***C=CCc(nc2C(OC)=O)c(cccn3)c3c2O*)cc1F)=O Chemical compound CC(C)(C)OC(NCc(cc1)c(***C=CCc(nc2C(OC)=O)c(cccn3)c3c2O*)cc1F)=O 0.000 description 6
- ZAMUTRHBCUERKJ-UHFFFAOYSA-N CNS(CCCCCN)(=O)=O Chemical compound CNS(CCCCCN)(=O)=O ZAMUTRHBCUERKJ-UHFFFAOYSA-N 0.000 description 2
- HCGWCDVMXRHFRQ-UHFFFAOYSA-N CC(C)(C)OC(NCCCCN(CC1)CCN1c(nc1C(OC)=O)c(cccn2)c2c1OCc1ccccc1)=O Chemical compound CC(C)(C)OC(NCCCCN(CC1)CCN1c(nc1C(OC)=O)c(cccn2)c2c1OCc1ccccc1)=O HCGWCDVMXRHFRQ-UHFFFAOYSA-N 0.000 description 1
- UUEGXEMADNBIAK-UHFFFAOYSA-N CC(C)(C)OC(NCc(ccc(F)c1)c1C(NCCCCS(N(C)c(nc1C(O)=O)c(cccn2)c2c1OS(c1ccc(C)cc1)(=O)=O)(=O)=O)=O)=O Chemical compound CC(C)(C)OC(NCc(ccc(F)c1)c1C(NCCCCS(N(C)c(nc1C(O)=O)c(cccn2)c2c1OS(c1ccc(C)cc1)(=O)=O)(=O)=O)=O)=O UUEGXEMADNBIAK-UHFFFAOYSA-N 0.000 description 1
- ZAOVCLOYJIEVFA-UHFFFAOYSA-N CC(C)(C)OC(NCc(ccc(F)c1)c1OCCCCS(NC)(=O)=O)=O Chemical compound CC(C)(C)OC(NCc(ccc(F)c1)c1OCCCCS(NC)(=O)=O)=O ZAOVCLOYJIEVFA-UHFFFAOYSA-N 0.000 description 1
- JHOAWXLTTNQAHU-UHFFFAOYSA-N CCOC(CCCCOc1c(CNC(OC(C)(C)C)=O)ccc(F)c1)=O Chemical compound CCOC(CCCCOc1c(CNC(OC(C)(C)C)=O)ccc(F)c1)=O JHOAWXLTTNQAHU-UHFFFAOYSA-N 0.000 description 1
- SWRWJFDMLTVIKI-UHFFFAOYSA-N CNS(CCCCC(O)=O)(=O)=O Chemical compound CNS(CCCCC(O)=O)(=O)=O SWRWJFDMLTVIKI-UHFFFAOYSA-N 0.000 description 1
- NTRKNFGJLAGSEK-UHFFFAOYSA-N CNS(CCCCCl)(=O)=O Chemical compound CNS(CCCCCl)(=O)=O NTRKNFGJLAGSEK-UHFFFAOYSA-N 0.000 description 1
- JOEMIFWIDNWIPI-UHFFFAOYSA-N Oc1c2ncccc2c(NCCCCCCCNC(c2cc(F)ccc2CN2)=O)nc1C2=O Chemical compound Oc1c2ncccc2c(NCCCCCCCNC(c2cc(F)ccc2CN2)=O)nc1C2=O JOEMIFWIDNWIPI-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D471/12—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 three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/18—Bridged 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- 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
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- 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
- C07D471/12—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 three hetero rings
- C07D471/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D515/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D515/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D515/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D515/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D515/18—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09172853.5 | 2009-10-13 | ||
| EP09172853 | 2009-10-13 | ||
| PCT/EP2010/065300 WO2011045330A1 (en) | 2009-10-13 | 2010-10-13 | Macrocyclic integrase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20120087916A true KR20120087916A (ko) | 2012-08-07 |
Family
ID=41720665
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020127009345A Abandoned KR20120087916A (ko) | 2009-10-13 | 2010-10-13 | 마크로시클릭 인테그라제 억제제 |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8497270B2 (enExample) |
| EP (1) | EP2488521B1 (enExample) |
| JP (1) | JP5624148B2 (enExample) |
| KR (1) | KR20120087916A (enExample) |
| CN (1) | CN102574854B (enExample) |
| AU (1) | AU2010305805B2 (enExample) |
| BR (1) | BR112012008586A2 (enExample) |
| CA (1) | CA2777664C (enExample) |
| EA (1) | EA019558B1 (enExample) |
| ES (1) | ES2446720T3 (enExample) |
| IL (1) | IL218845A0 (enExample) |
| MX (1) | MX2012004426A (enExample) |
| NZ (1) | NZ598766A (enExample) |
| WO (1) | WO2011045330A1 (enExample) |
| ZA (1) | ZA201202516B (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2487176A1 (en) * | 2011-02-14 | 2012-08-15 | Elanco Animal Health Ireland Limited | Macrocyclic integrase inhibitors for use in the treatment of feline immunodeficiency virus |
| WO2014008636A1 (en) * | 2012-07-11 | 2014-01-16 | Merck Sharp & Dohme Corp. | Macrocyclic compounds as hiv integrase inhibitors |
| EP2931730B1 (en) | 2012-12-17 | 2019-08-07 | Merck Sharp & Dohme Corp. | 4-pyridinonetriazine derivatives as hiv integrase inhibitors |
| US9493479B2 (en) | 2013-04-16 | 2016-11-15 | Merck Sharp & Dohme Corp. | Substituted pyrido[1,2-a]pyrazines as HIV integrase inhibitors |
| SI2997033T1 (en) | 2013-05-17 | 2018-04-30 | Merck Sharp & Dohme Corp. | FUZYCLE TRICYCLE HETEROCYCLIC COMPOUNDS AS HIV INTEGRATED INHIBITORS |
| US9951079B2 (en) | 2013-06-13 | 2018-04-24 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds as HIV integrase inhibitors |
| CA2924829C (en) | 2013-09-27 | 2019-10-29 | Merck Sharp & Dohme Corp. | Substituted quinolizine derivatives useful as hiv integrase inhibitors |
| WO2015112806A2 (en) | 2014-01-24 | 2015-07-30 | Tp Therapeutics, Inc. | Diaryl macrocycles as modulators of protein kinases |
| WO2016187788A1 (en) | 2015-05-25 | 2016-12-01 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds useful for treating hiv infection |
| RU2732405C2 (ru) | 2015-07-02 | 2020-09-16 | Тёрнинг Поинт Терапьютикс, Инк. | Хиральные диарильные макроциклы в качестве модуляторов протеинкиназ |
| BR112018000297A2 (pt) | 2015-07-06 | 2018-09-04 | Tp Therapeutics Inc | polimorfo de macrociclo de diarila |
| WO2017015367A1 (en) | 2015-07-21 | 2017-01-26 | Tp Therapeutics, Inc. | Chiral diaryl macrocycles and uses thereof |
| US10548910B2 (en) | 2015-11-17 | 2020-02-04 | Merck Sharp & Dohme Corp. | Amido-substituted pyridotriazine derivatives useful as HIV integrase inhibitors |
| EP3389380B1 (en) | 2015-12-15 | 2021-07-21 | Merck Sharp & Dohme Corp. | Spirocyclic quinolizine derivatives useful as hiv integrase inhibitors |
| WO2017113288A1 (en) | 2015-12-31 | 2017-07-06 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds as hiv integrase inhibitors |
| JOP20190130A1 (ar) | 2016-12-02 | 2019-06-02 | Merck Sharp & Dohme | مركبات حلقية غير متجانسة رباعية الحلقات مفيدة كمثبطات إنزيم مدمج لفيروس نقص المناعة البشرية (hiv) |
| WO2018102634A1 (en) | 2016-12-02 | 2018-06-07 | Merck Sharp & Dohme Corp. | Tricyclic heterocycle compounds useful as hiv integrase inhibitors |
| TWI808958B (zh) | 2017-01-25 | 2023-07-21 | 美商特普醫葯公司 | 涉及二芳基巨環化合物之組合療法 |
| WO2018140368A1 (en) | 2017-01-26 | 2018-08-02 | Merck Sharp & Dohme Corp. | Substituted quinolizine derivatives useful as hiv integrase inhibitors |
| PT3658148T (pt) | 2017-07-28 | 2024-08-26 | Turning Point Therapeutics Inc | Compostos macrocíclicos e utilizações dos mesmos |
| RS63787B1 (sr) | 2017-12-19 | 2022-12-30 | Turning Point Therapeutics Inc | Makrociklična jedinjenja za lečenje bolesti |
| KR20240151256A (ko) | 2019-03-22 | 2024-10-17 | 길리애드 사이언시즈, 인코포레이티드 | 가교된 트리시클릭 카르바모일피리돈 화합물 및 그의 제약 용도 |
| EP4110783A1 (en) | 2020-02-24 | 2023-01-04 | Gilead Sciences, Inc. | Tetracyclic compounds for treating hiv infection |
| CN116390924B (zh) | 2020-09-30 | 2025-11-07 | 吉利德科学公司 | 桥连三环氨基甲酰基吡啶酮化合物及其用途 |
| CN112358477A (zh) * | 2020-11-10 | 2021-02-12 | 牡丹江医学院 | 一种用于治疗胆囊炎的药物及其制备方法 |
| CR20260070A (es) | 2021-01-19 | 2026-04-24 | Gilead Sciences Inc | COMPUESTOS DE PIRIDOTRIAZINA SUSTITUIDOS Y USOS DE ESTOS (Divisional 2023-0315) |
| TWI856796B (zh) | 2022-04-06 | 2024-09-21 | 美商基利科學股份有限公司 | 橋聯三環胺甲醯基吡啶酮化合物及其用途 |
| CN115974886A (zh) * | 2022-11-22 | 2023-04-18 | 国科大杭州高等研究院 | 一种含有二氢苯并呋喃骨架的大环内酰胺化合物及其制备方法 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CS210880B1 (cs) | 1979-10-19 | 1982-01-29 | Jiri Krepelka | Substituované imidy kyselin 4-arylnaftalen-2,3-dikarboxylových |
| CS225002B1 (cs) | 1980-12-12 | 1984-02-13 | Krepelka Jiri | Deriváty 9-fenyl-1H-benzo/f/isoindol-1,3-dionu a způsob jejich výroby |
| JPH04217684A (ja) | 1990-05-30 | 1992-08-07 | Shionogi & Co Ltd | アルド−ス還元酵素阻害物質 |
| EP0729950A4 (en) * | 1994-09-13 | 2001-02-07 | Kyowa Hakko Kogyo Kk | ANTI-HIV MEDICINAL PRODUCTS |
| AU1532802A (en) | 2000-10-12 | 2002-04-22 | Merck & Co Inc | Aza- and polyaza-naphthalenyl-carboxamides useful as hiv integrase inhibitors |
| JP2004517860A (ja) | 2000-10-12 | 2004-06-17 | メルク エンド カムパニー インコーポレーテッド | Ｈｉｖインテグラーゼ阻害薬として有用なアザ−およびポリアザ−ナフタレニルカルボキサミド類 |
| AU2002230392A1 (en) | 2000-10-12 | 2002-05-15 | Merck & Co., Inc. | AZA-and polyaza-naphthalenyl ketones useful as HIV integrase inhibitors |
| EP1326865B1 (en) | 2000-10-12 | 2009-05-06 | Merck & Co., Inc. | Aza- and polyaza-naphthalenyl carboxamides useful as hiv integrase inhibitors |
| AU2003301439A1 (en) | 2002-10-16 | 2004-05-04 | Gilead Sciences, Inc. | Pre-organized tricyclic integrase inhibitor compounds |
| US7176220B2 (en) | 2002-11-20 | 2007-02-13 | Japan Tobacco Inc. | 4-oxoquinoline compound and use thereof as pharmaceutical agent |
| WO2004058756A1 (en) | 2002-12-27 | 2004-07-15 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Tetrahydro-4h-pyrido[1,2-a]pyrimidines and related compounds useful as hiv integrase inhibitors |
| US6890942B2 (en) | 2003-05-16 | 2005-05-10 | Bristol-Myers Squibb Company | Acyl sulfonamides as inhibitors of HIV integrase |
| ATE433974T1 (de) | 2003-09-19 | 2009-07-15 | Gilead Sciences Inc | Azachinolinolphosphonatverbindungen als integraseinhibitoren |
| AU2005221864A1 (en) | 2004-03-09 | 2005-09-22 | Istituto Di Ricerche Di Biologia Molecolare P Angeletti Spa | HIV integrase inhibitors |
| US7176196B2 (en) | 2004-05-28 | 2007-02-13 | Bristol-Myers Squibb Company | Bicyclic heterocycles as HIV integrase inhibitors |
| DK3187225T3 (da) | 2005-04-28 | 2022-02-28 | Viiv Healthcare Co | Polycyklisk carbamoylpyridonderivat med hiv-integrasehæmmende aktivitet |
| US20080214527A1 (en) * | 2005-08-04 | 2008-09-04 | Takashi Kawasuji | Hiv Integrase Inhibitors |
| TW200800988A (en) * | 2005-10-27 | 2008-01-01 | Shionogi & Amp Co Ltd | Polycyclic carbamoylpyridone derivative having HIV integrase inhibitory activity |
| US8039458B2 (en) * | 2005-11-17 | 2011-10-18 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| TW200811153A (en) | 2006-06-23 | 2008-03-01 | Japan Tobacco Inc | 6-(heterocyclyl-substituted benzyl)-4-oxoquinoline compound and use thereof as HIV integrase inhibitor |
| WO2009112439A1 (en) * | 2008-03-10 | 2009-09-17 | Janssen Pharmaceutica Nv | 4-aryl-2-anilino-pyrimidines as plk kinase inhibitors |
-
2010
- 2010-10-13 WO PCT/EP2010/065300 patent/WO2011045330A1/en not_active Ceased
- 2010-10-13 EP EP10772998.0A patent/EP2488521B1/en active Active
- 2010-10-13 NZ NZ598766A patent/NZ598766A/xx not_active IP Right Cessation
- 2010-10-13 US US13/395,891 patent/US8497270B2/en active Active
- 2010-10-13 EA EA201270540A patent/EA019558B1/ru not_active IP Right Cessation
- 2010-10-13 BR BR112012008586A patent/BR112012008586A2/pt not_active IP Right Cessation
- 2010-10-13 CN CN201080046163.3A patent/CN102574854B/zh active Active
- 2010-10-13 AU AU2010305805A patent/AU2010305805B2/en active Active
- 2010-10-13 KR KR1020127009345A patent/KR20120087916A/ko not_active Abandoned
- 2010-10-13 CA CA2777664A patent/CA2777664C/en active Active
- 2010-10-13 MX MX2012004426A patent/MX2012004426A/es active IP Right Grant
- 2010-10-13 ES ES10772998.0T patent/ES2446720T3/es active Active
- 2010-10-13 JP JP2012533614A patent/JP5624148B2/ja active Active
-
2012
- 2012-03-26 IL IL218845A patent/IL218845A0/en unknown
- 2012-04-05 ZA ZA2012/02516A patent/ZA201202516B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2011045330A1 (en) | 2011-04-21 |
| NZ598766A (en) | 2013-09-27 |
| MX2012004426A (es) | 2012-07-30 |
| EP2488521A1 (en) | 2012-08-22 |
| CA2777664A1 (en) | 2011-04-21 |
| CN102574854B (zh) | 2014-04-16 |
| JP2013507423A (ja) | 2013-03-04 |
| EA201270540A1 (ru) | 2012-09-28 |
| EA019558B1 (ru) | 2014-04-30 |
| IL218845A0 (en) | 2012-06-28 |
| ES2446720T3 (es) | 2014-03-10 |
| US8497270B2 (en) | 2013-07-30 |
| CA2777664C (en) | 2014-06-10 |
| JP5624148B2 (ja) | 2014-11-12 |
| AU2010305805B2 (en) | 2014-04-03 |
| AU2010305805A1 (en) | 2012-04-19 |
| CN102574854A (zh) | 2012-07-11 |
| ZA201202516B (en) | 2013-09-25 |
| BR112012008586A2 (pt) | 2016-11-29 |
| EP2488521B1 (en) | 2013-12-18 |
| US20120172367A1 (en) | 2012-07-05 |
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