CN102325752B - 咔唑和咔啉激酶抑制剂 - Google Patents
咔唑和咔啉激酶抑制剂 Download PDFInfo
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- CN102325752B CN102325752B CN200980157175.0A CN200980157175A CN102325752B CN 102325752 B CN102325752 B CN 102325752B CN 200980157175 A CN200980157175 A CN 200980157175A CN 102325752 B CN102325752 B CN 102325752B
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- Prior art keywords
- substituted
- alkyl
- carbazole
- pyrido
- indole
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- 0 C*1CC(CC2)OC2C1 Chemical compound C*1CC(CC2)OC2C1 0.000 description 20
- HMBMNRWNTPVYMY-UHFFFAOYSA-N CC(C)(C)OC(N(CC1)CC=C1c1ccc(c(cc(cc2C(N)=O)-c3ccc(CN4CCOCC4)c(C)c3)c2[nH]2)c2c1)=O Chemical compound CC(C)(C)OC(N(CC1)CC=C1c1ccc(c(cc(cc2C(N)=O)-c3ccc(CN4CCOCC4)c(C)c3)c2[nH]2)c2c1)=O HMBMNRWNTPVYMY-UHFFFAOYSA-N 0.000 description 1
- VNVGPWCTZDRNME-UHFFFAOYSA-N CC(C)(C)OC(N(CC1)CCN1c(cc1)cc2c1c(cc(cc1C(N)=O)Br)c1[nH]2)=O Chemical compound CC(C)(C)OC(N(CC1)CCN1c(cc1)cc2c1c(cc(cc1C(N)=O)Br)c1[nH]2)=O VNVGPWCTZDRNME-UHFFFAOYSA-N 0.000 description 1
- HDKRJCLEHOEVDY-UHFFFAOYSA-O CC(C)OC(c(cc1)cc2c1c(nc(cc1C([NH3+])=O)-c3ccccc3)c1[nH]2)=O Chemical compound CC(C)OC(c(cc1)cc2c1c(nc(cc1C([NH3+])=O)-c3ccccc3)c1[nH]2)=O HDKRJCLEHOEVDY-UHFFFAOYSA-O 0.000 description 1
- HACDQHWPWBOTLR-UHFFFAOYSA-N CCOC(c1nc(-c2ccccc2)cnn1)=O Chemical compound CCOC(c1nc(-c2ccccc2)cnn1)=O HACDQHWPWBOTLR-UHFFFAOYSA-N 0.000 description 1
- CRTFXDWOWZNUCM-UHFFFAOYSA-N CNC(c(cc1)cc2c1c(nc(cc1C(OC)=O)Br)c1[nH]2)=O Chemical compound CNC(c(cc1)cc2c1c(nc(cc1C(OC)=O)Br)c1[nH]2)=O CRTFXDWOWZNUCM-UHFFFAOYSA-N 0.000 description 1
- AWUBNIORUGPGCH-UHFFFAOYSA-N CNc1cccc(-c(cc2)cc(C#N)c2Nc(cc2)ccc2C(N2CCN(C)CC2)=[U])c1 Chemical compound CNc1cccc(-c(cc2)cc(C#N)c2Nc(cc2)ccc2C(N2CCN(C)CC2)=[U])c1 AWUBNIORUGPGCH-UHFFFAOYSA-N 0.000 description 1
- OXQBKAKFIPZSRK-UHFFFAOYSA-N COC(c1cc(-c(cc2F)ccc2OC)nc2c1[n](Cc(cc1)ccc1O)c1c2ccc(Cl)c1)=O Chemical compound COC(c1cc(-c(cc2F)ccc2OC)nc2c1[n](Cc(cc1)ccc1O)c1c2ccc(Cl)c1)=O OXQBKAKFIPZSRK-UHFFFAOYSA-N 0.000 description 1
- OTCRFTKWRXBOKH-UHFFFAOYSA-N COC(c1cc(-c2cc(Cl)ccc2)nc2c1[nH]c1nc(N3CCOCC3)ccc21)=O Chemical compound COC(c1cc(-c2cc(Cl)ccc2)nc2c1[nH]c1nc(N3CCOCC3)ccc21)=O OTCRFTKWRXBOKH-UHFFFAOYSA-N 0.000 description 1
- OUPLCOBTNGKXLA-UHFFFAOYSA-N COC(c1cccc(Nc(c(C#N)c2)ccc2-c2cccc(OC)c2)c1)=O Chemical compound COC(c1cccc(Nc(c(C#N)c2)ccc2-c2cccc(OC)c2)c1)=O OUPLCOBTNGKXLA-UHFFFAOYSA-N 0.000 description 1
- WYYJFBQEOAETOC-UHFFFAOYSA-N C[NH+](C(C(C1)C([N]#C)=C(C(CC2)C=CC2Cl)NC1Br)O)[O-] Chemical compound C[NH+](C(C(C1)C([N]#C)=C(C(CC2)C=CC2Cl)NC1Br)O)[O-] WYYJFBQEOAETOC-UHFFFAOYSA-N 0.000 description 1
- GJVNFZGZPOGEEL-UHFFFAOYSA-N Cc(cc1)ncc1-c(cc1C(N)=O)cc2c1[nH]c1cc(N)ccc21 Chemical compound Cc(cc1)ncc1-c(cc1C(N)=O)cc2c1[nH]c1cc(N)ccc21 GJVNFZGZPOGEEL-UHFFFAOYSA-N 0.000 description 1
- SYQVOBVELSAQNP-UHFFFAOYSA-O Cc1cc(-c(cc2C([NH3+])=O)nc3c2[nH]c2c3ccc(OCCN3CCOCC3)c2)ccc1 Chemical compound Cc1cc(-c(cc2C([NH3+])=O)nc3c2[nH]c2c3ccc(OCCN3CCOCC3)c2)ccc1 SYQVOBVELSAQNP-UHFFFAOYSA-O 0.000 description 1
- PAOOJSSSLWVXRS-UHFFFAOYSA-N Clc1cc(Br)ccc1CN1CCOCC1 Chemical compound Clc1cc(Br)ccc1CN1CCOCC1 PAOOJSSSLWVXRS-UHFFFAOYSA-N 0.000 description 1
- OPNYOLYMRNWGTQ-UHFFFAOYSA-N N#Cc1cc(-c(cc2F)ccc2F)ccc1Nc(cc1)ccc1C(N1CCOCC1)=O Chemical compound N#Cc1cc(-c(cc2F)ccc2F)ccc1Nc(cc1)ccc1C(N1CCOCC1)=O OPNYOLYMRNWGTQ-UHFFFAOYSA-N 0.000 description 1
- ULRRXHOQWYBPDQ-UHFFFAOYSA-N NC(c1c2[nH]c3cc(C(N4CCOCCC4)=O)ccc3c2nc(-c2ccccc2)c1)=O Chemical compound NC(c1c2[nH]c3cc(C(N4CCOCCC4)=O)ccc3c2nc(-c2ccccc2)c1)=O ULRRXHOQWYBPDQ-UHFFFAOYSA-N 0.000 description 1
- DCGMYTVQQYBPMD-UHFFFAOYSA-N NC(c1cc(-c(cc2Cl)ccc2F)cc2c1[nH]c1cc(C(N3CCOCC3)=O)ccc21)=O Chemical compound NC(c1cc(-c(cc2Cl)ccc2F)cc2c1[nH]c1cc(C(N3CCOCC3)=O)ccc21)=O DCGMYTVQQYBPMD-UHFFFAOYSA-N 0.000 description 1
- ICJRHNDSABMBDB-UHFFFAOYSA-N NC(c1cc(-c(cc2Cl)ccc2OCCN2CCOCC2)cc2c1[nH]c1cc(N(CC3)CCS3(=O)=O)ccc21)=O Chemical compound NC(c1cc(-c(cc2Cl)ccc2OCCN2CCOCC2)cc2c1[nH]c1cc(N(CC3)CCS3(=O)=O)ccc21)=O ICJRHNDSABMBDB-UHFFFAOYSA-N 0.000 description 1
- DHWJRBLFSQSGJU-UHFFFAOYSA-N NC(c1cc(-c2ccc(CN3CCOCC3)c(Cl)c2)cc2c1[nH]c1cc(-c(cc3)cnc3N3CCOCC3)ccc21)=O Chemical compound NC(c1cc(-c2ccc(CN3CCOCC3)c(Cl)c2)cc2c1[nH]c1cc(-c(cc3)cnc3N3CCOCC3)ccc21)=O DHWJRBLFSQSGJU-UHFFFAOYSA-N 0.000 description 1
- SFBKXIQANIRERX-UHFFFAOYSA-N OC(c1c2[nH]c(cc(cc3)OCc4ccccc4)c3c2nc(-c(cc2)ccc2Cl)c1)=O Chemical compound OC(c1c2[nH]c(cc(cc3)OCc4ccccc4)c3c2nc(-c(cc2)ccc2Cl)c1)=O SFBKXIQANIRERX-UHFFFAOYSA-N 0.000 description 1
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles 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 carbon atoms of the ring system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- 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
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- 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
- C07D401/06—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 only aliphatic carbon atoms
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- 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
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- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
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- 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
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- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13904208P | 2008-12-19 | 2008-12-19 | |
| US61/139,042 | 2008-12-19 | ||
| PCT/US2009/068394 WO2010080474A1 (en) | 2008-12-19 | 2009-12-17 | Carbazole and carboline kinase inhibitors |
Publications (2)
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| US8084620B2 (en) | 2008-12-19 | 2011-12-27 | Bristol-Myers Squibb Company | Carbazole carboxamide compounds useful as kinase inhibitors |
| AU2010289497B2 (en) | 2009-09-03 | 2016-04-14 | Bristol-Myers Squibb Company | JAK2 inhibitors and their use for the treatment of myeloproliferative diseases and cancer |
| EP2961747B1 (en) | 2013-02-27 | 2017-11-15 | Bristol-Myers Squibb Company | Carbazole compounds useful as bromodomain inhibitors |
| US9492460B2 (en) * | 2013-02-27 | 2016-11-15 | Bristol-Myers Squibb Company | Carbazole compounds useful as bromodomain inhibitors |
| CN105492444B (zh) * | 2013-07-02 | 2018-09-07 | 百时美施贵宝公司 | 作为rock抑制剂的三环吡啶-甲酰胺衍生物 |
| EP3016950B1 (en) * | 2013-07-02 | 2017-06-07 | Bristol-Myers Squibb Company | Tricyclic pyrido-carboxamide derivatives as rock inhibitors |
| GB201317363D0 (en) | 2013-10-01 | 2013-11-13 | Eisai Ltd | Novel compounds |
| EA201990240A1 (ru) * | 2013-12-24 | 2019-06-28 | Бристол-Маерс Сквибб Компани | Новые трициклические соединения в качестве противораковых средств |
| US9458156B2 (en) | 2014-12-23 | 2016-10-04 | Bristol-Myers Squibb Company | Tricyclic compounds as anticancer agents |
| EA036518B1 (ru) * | 2015-02-02 | 2020-11-18 | Юсб Байофарма Спрл | Производные 9h-пирролодипиридина |
| GB201512678D0 (en) * | 2015-07-20 | 2015-08-26 | Wista Lab Ltd | Methods of chemical synthesis |
| MA52119A (fr) | 2015-10-19 | 2018-08-29 | Ncyte Corp | Composés hétérocycliques utilisés comme immunomodulateurs |
| PT3377488T (pt) | 2015-11-19 | 2022-11-21 | Incyte Corp | Compostos heterocíclicos como imunomoduladores |
| SI3394033T1 (sl) | 2015-12-22 | 2021-03-31 | Incyte Corporation | Heterociklične spojine kot imunomodulatorji |
| WO2017192961A1 (en) | 2016-05-06 | 2017-11-09 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| EP3464279B1 (en) | 2016-05-26 | 2021-11-24 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| PL3472167T3 (pl) | 2016-06-20 | 2022-12-19 | Incyte Corporation | Związki heterocykliczne jako immunomodulatory |
| KR102625861B1 (ko) * | 2016-06-28 | 2024-01-17 | 삼성디스플레이 주식회사 | 헤테로시클릭 화합물 및 이를 포함한 유기 발광 소자 |
| EP3484866B1 (en) | 2016-07-14 | 2022-09-07 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| ES2941716T3 (es) | 2016-08-29 | 2023-05-25 | Incyte Corp | Compuestos heterocíclicos como inmunomoduladores |
| US20180179201A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| KR102696516B1 (ko) | 2016-12-22 | 2024-08-22 | 인사이트 코포레이션 | 면역조절제로서의 벤조옥사졸 유도체 |
| EP3558973B1 (en) | 2016-12-22 | 2021-09-15 | Incyte Corporation | Pyridine derivatives as immunomodulators |
| WO2018119286A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Bicyclic heteroaromatic compounds as immunomodulators |
| EP4212529B1 (en) | 2018-03-30 | 2025-01-29 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| FI4219492T3 (fi) | 2018-05-11 | 2025-02-17 | Incyte Corp | Heterosyklisiä yhdisteitä immunomodulaattoreina |
| GB201809102D0 (en) * | 2018-06-04 | 2018-07-18 | Univ Oxford Innovation Ltd | Compounds |
| US10947253B2 (en) | 2019-08-05 | 2021-03-16 | Ankh Life Sciences Limited | Fused polycyclic dimers |
| CA3150434A1 (en) | 2019-08-09 | 2021-02-18 | Incyte Corporation | Salts of a pd-1/pd-l1 inhibitor |
| US20220372135A1 (en) | 2019-09-27 | 2022-11-24 | Disc Medicine, Inc. | Methods for treating myelofibrosis and related conditions |
| AR120109A1 (es) | 2019-09-30 | 2022-02-02 | Incyte Corp | Compuestos de pirido[3,2-d]pirimidina como inmunomoduladores |
| JP7545467B2 (ja) * | 2019-10-04 | 2024-09-04 | ブリストル-マイヤーズ スクイブ カンパニー | 置換カルバゾール化合物 |
| IL292524A (en) | 2019-11-11 | 2022-06-01 | Incyte Corp | Salts and crystalline forms of a pd-1/pd-l1 inhibitor |
| US12129265B2 (en) | 2020-07-21 | 2024-10-29 | Ankh Life Sciences Limited | Therapeutic agents and uses thereof |
| WO2022099075A1 (en) | 2020-11-06 | 2022-05-12 | Incyte Corporation | Crystalline form of a pd-1/pd-l1 inhibitor |
| PE20231438A1 (es) | 2020-11-06 | 2023-09-14 | Incyte Corp | Proceso para hacer un inhibidor de pd-1/pd-l1 y sales y formas cristalinas del mismo |
| US11780836B2 (en) | 2020-11-06 | 2023-10-10 | Incyte Corporation | Process of preparing a PD-1/PD-L1 inhibitor |
| CN113880836B (zh) * | 2021-10-18 | 2023-03-14 | 浙江中医药大学 | 1,5,8-三取代γ-咔啉类衍生物及其制备方法和应用 |
| EP4434968A4 (en) * | 2021-11-19 | 2025-10-22 | Nain Biotech Hangzhou Co Ltd | TETRAHYDROCARBAZOLE COMPOUND, PHARMACEUTICAL COMPOSITION AND USE THEREOF |
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| US20050165029A1 (en) * | 2004-01-13 | 2005-07-28 | Ambit Biosciences Corporation | Pyrrolopyrimidine derivatives and analogs and their use in the treatment and prevention of diseases |
| AU2006316322B2 (en) * | 2005-11-22 | 2011-08-25 | Merck Canada Inc. | Tricyclic compounds useful as inhibitors of kinases |
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- 2009-12-17 WO PCT/US2009/068394 patent/WO2010080474A1/en not_active Ceased
- 2009-12-17 CN CN200980157175.0A patent/CN102325752B/zh not_active Expired - Fee Related
- 2009-12-17 ES ES09793679.3T patent/ES2490867T3/es active Active
- 2009-12-17 EP EP09793679.3A patent/EP2370407B1/en not_active Not-in-force
- 2009-12-17 JP JP2011542419A patent/JP5557849B2/ja not_active Expired - Fee Related
- 2009-12-17 US US13/140,184 patent/US8815840B2/en active Active
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| US5532261A (en) * | 1994-12-12 | 1996-07-02 | Merck & Co., Inc. | Carbapenem antibiotics, compositions containing such compounds and methods of use |
| WO2006034317A2 (en) * | 2004-09-21 | 2006-03-30 | Glaxo Group Limited | Chemical compounds |
| WO2007005534A2 (en) * | 2005-06-30 | 2007-01-11 | Smithkline Beecham Corporation | Chemical compounds |
| WO2007076286A2 (en) * | 2005-12-16 | 2007-07-05 | Smithkline Beecham Corporation | Chemical compounds |
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| US20120058988A1 (en) | 2012-03-08 |
| EP2370407A1 (en) | 2011-10-05 |
| JP2012512886A (ja) | 2012-06-07 |
| CN102325752A (zh) | 2012-01-18 |
| EP2370407B1 (en) | 2014-06-18 |
| JP5557849B2 (ja) | 2014-07-23 |
| ES2490867T3 (es) | 2014-09-04 |
| US8815840B2 (en) | 2014-08-26 |
| WO2010080474A1 (en) | 2010-07-15 |
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