ES2436241T3 - Compuestos de espiropiperidina como antagonistas de receptor oral-1 - Google Patents
Compuestos de espiropiperidina como antagonistas de receptor oral-1 Download PDFInfo
- Publication number
- ES2436241T3 ES2436241T3 ES10782486T ES10782486T ES2436241T3 ES 2436241 T3 ES2436241 T3 ES 2436241T3 ES 10782486 T ES10782486 T ES 10782486T ES 10782486 T ES10782486 T ES 10782486T ES 2436241 T3 ES2436241 T3 ES 2436241T3
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- ES
- Spain
- Prior art keywords
- methyl
- pyrazol
- fluoro
- mmol
- piperidine
- Prior art date
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- 229940044551 receptor antagonist Drugs 0.000 title description 6
- 239000002464 receptor antagonist Substances 0.000 title description 6
- JUXAVSAMVBLDKO-UHFFFAOYSA-N 1-(1-azabicyclo[2.2.2]octan-3-yl)-3-[3-(1h-indol-3-yl)-1-oxo-1-spiro[1,2-dihydroindene-3,4'-piperidine]-1'-ylpropan-2-yl]urea Chemical class C1N(CC2)CCC2C1NC(=O)NC(C(=O)N1CCC2(C3=CC=CC=C3CC2)CC1)CC1=CNC2=CC=CC=C12 JUXAVSAMVBLDKO-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 219
- -1 chloro, cyano, cyanomethyl Chemical group 0.000 claims abstract description 146
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 111
- 150000003839 salts Chemical class 0.000 claims abstract description 43
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 34
- 239000001257 hydrogen Substances 0.000 claims abstract description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 19
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 12
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 12
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims abstract description 7
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
- 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 claims abstract description 3
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000004849 alkoxymethyl group Chemical group 0.000 claims abstract description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
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- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 3
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- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims abstract 2
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- ALDFBAMFJCZMRT-UHFFFAOYSA-N 1-[2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-3-fluorophenyl]ethanone Chemical compound CC(=O)C1=CC=CC(F)=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)=C1 ALDFBAMFJCZMRT-UHFFFAOYSA-N 0.000 claims description 2
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- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 description 1
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000007830 receptor-based assay Methods 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 239000002485 serotonin 2C agonist Substances 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- SGNDLCOSZVJOET-UHFFFAOYSA-M sodium;hydrogen carbonate;hypochlorous acid Chemical compound [Na+].ClO.OC([O-])=O SGNDLCOSZVJOET-UHFFFAOYSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010972 statistical evaluation Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000004808 supercritical fluid chromatography Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- QMKKTVXAYUUJAA-UHFFFAOYSA-N tert-butyl 1-(2-fluorophenyl)-3-methylpyrazole-4-carboxylate Chemical compound C1=C(C(=O)OC(C)(C)C)C(C)=NN1C1=CC=CC=C1F QMKKTVXAYUUJAA-UHFFFAOYSA-N 0.000 description 1
- DUAYKFWVNCCEHS-UHFFFAOYSA-N tert-butyl 2,4,4-trifluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC21C(SC(F)=C1)=C1C(F)(F)CO2 DUAYKFWVNCCEHS-UHFFFAOYSA-N 0.000 description 1
- JKUYRAMKJLMYLO-UHFFFAOYSA-N tert-butyl 3-oxobutanoate Chemical compound CC(=O)CC(=O)OC(C)(C)C JKUYRAMKJLMYLO-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- OTFQSEYOEXRUEB-UHFFFAOYSA-N tert-butyl n-cyclopropyl-n-[[3-fluoro-2-[4-(hydroxymethyl)-3-methylpyrazol-1-yl]phenyl]methyl]carbamate Chemical compound C1=C(CO)C(C)=NN1C1=C(F)C=CC=C1CN(C(=O)OC(C)(C)C)C1CC1 OTFQSEYOEXRUEB-UHFFFAOYSA-N 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- JAELLLITIZHOGQ-UHFFFAOYSA-N tert-butyl propanoate Chemical compound CCC(=O)OC(C)(C)C JAELLLITIZHOGQ-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001550 time effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/20—Spiro-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
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
-
- 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
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Child & Adolescent Psychology (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09382245 | 2009-11-16 | ||
| EP09382245 | 2009-11-16 | ||
| US29862810P | 2010-01-27 | 2010-01-27 | |
| US298628P | 2010-01-27 | ||
| PCT/US2010/056449 WO2011060217A1 (en) | 2009-11-16 | 2010-11-12 | Spiropiperidine compounds as orl-1 receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2436241T3 true ES2436241T3 (es) | 2013-12-27 |
Family
ID=41800752
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10782486T Active ES2436241T3 (es) | 2009-11-16 | 2010-11-12 | Compuestos de espiropiperidina como antagonistas de receptor oral-1 |
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| Country | Link |
|---|---|
| US (1) | US20120214784A1 (enExample) |
| EP (1) | EP2501704B1 (enExample) |
| JP (1) | JP5723381B2 (enExample) |
| KR (1) | KR101368130B1 (enExample) |
| CN (1) | CN102666550B (enExample) |
| AU (1) | AU2010319400B2 (enExample) |
| BR (1) | BR112012011710A2 (enExample) |
| CA (1) | CA2781041C (enExample) |
| DK (1) | DK2501704T3 (enExample) |
| EA (1) | EA020391B1 (enExample) |
| ES (1) | ES2436241T3 (enExample) |
| HR (1) | HRP20130969T1 (enExample) |
| MX (1) | MX2012005690A (enExample) |
| PL (1) | PL2501704T3 (enExample) |
| PT (1) | PT2501704E (enExample) |
| RS (1) | RS53017B (enExample) |
| SI (1) | SI2501704T1 (enExample) |
| WO (1) | WO2011060217A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT3252057T (pt) | 2009-12-04 | 2024-06-04 | Sunovion Pharmaceuticals Inc | Compostos multicíclicos e métodos de utilização dos mesmos |
| TWI582096B (zh) * | 2011-12-06 | 2017-05-11 | 美國禮來大藥廠 | 用於酒精依賴及濫用處理之４',５'－二氫螺［哌啶－４,７'－噻吩并[２，３－c]哌喃］化合物 |
| TW201416370A (zh) | 2012-07-31 | 2014-05-01 | Lilly Co Eli | 用於治療焦慮之ｏｒｌ－１受體拮抗劑 |
| WO2014078568A1 (en) | 2012-11-14 | 2014-05-22 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| JO3638B1 (ar) * | 2015-09-09 | 2020-08-27 | Lilly Co Eli | مركبات مفيدة في تثبيط ror - جاما- t |
| EA201990400A1 (ru) | 2016-07-29 | 2019-07-31 | Суновион Фармасьютикалз, Инк. | Соединения и композиции и их применение |
| MX2019000982A (es) | 2016-07-29 | 2019-07-04 | Sunovion Pharmaceuticals Inc | Compuestos y composiciones y usos de los mismos. |
| AU2017309725A1 (en) | 2016-08-10 | 2019-02-21 | Bayer Cropscience Aktiengesellschaft | Substituted 2-heterocyclyl imidazolyl-carboxamides as pest control agents |
| CN116808023A (zh) | 2017-02-16 | 2023-09-29 | 桑诺维恩药品公司 | 治疗精神分裂症的方法 |
| US10603320B2 (en) * | 2017-03-02 | 2020-03-31 | Eli Lilly And Company | Compounds useful for inhibiting ROR-gamma-t |
| HUE054483T2 (hu) | 2017-03-02 | 2021-09-28 | Lilly Co Eli | ROR-gamma-T gátlására alkalmas vegyületek |
| JP7191085B2 (ja) | 2017-08-02 | 2022-12-16 | サノビオン ファーマシューティカルズ インク | イソクロマン化合物およびその使用 |
| MX2020008537A (es) | 2018-02-16 | 2021-01-08 | Sunovion Pharmaceuticals Inc | Sales, formas cristalinas y metodos de produccion de las mismas. |
| IL283592B2 (en) | 2018-12-17 | 2025-08-01 | Vertex Pharma | Inhibitors of apol1 and methods of using same |
| CN113784755B (zh) | 2019-03-14 | 2024-05-10 | 赛诺维信制药公司 | 异色满基化合物的盐及其结晶形式、制备方法、治疗用途和药物组合物 |
| EP3766879A1 (en) | 2019-07-19 | 2021-01-20 | Basf Se | Pesticidal pyrazole derivatives |
| CA3180115A1 (en) | 2020-04-14 | 2021-10-21 | Sunovion Pharmaceuticals Inc. | (s)-(4,5-dihydro-7h-thieno[2,3-c]pyran-7-yl)-n-methylmethanamine for treating neurological and psychiatric disorders |
| EP4165036A1 (en) | 2020-06-12 | 2023-04-19 | Vertex Pharmaceuticals Incorporated | Solid forms of apol1 inhibitor and using the same |
| UY39395A (es) | 2020-08-26 | 2022-03-31 | Vertex Pharma | Inhibidores de apol1 y métodos para usar los mismos |
| CA3251050A1 (en) * | 2022-02-08 | 2023-08-17 | Vertex Pharmaceuticals Incorporated | 2-METHYL-4',5'-DIHYDROSPIRO[PIPERIDINE-4,7'-THIENO[2,3-C]PYRAN] DERIVATIVES USED AS APOL1 INHIBITORS AND THEIR METHODS OF USE |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003235912A1 (en) | 2002-05-10 | 2003-11-11 | Taisho Pharmaceutical Co., Ltd. | Spiro-ring compound |
| WO2005016913A1 (en) * | 2003-08-19 | 2005-02-24 | Pfizer Japan, Inc. | Tetrahydroisoquinoline or isochroman compounds as orl-1 receptor ligands for the treatment of pain and cns disorders |
| DE10360792A1 (de) * | 2003-12-23 | 2005-07-28 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| EP1732928A2 (en) * | 2004-03-29 | 2006-12-20 | Pfizer, Inc. | Alpha aryl or heteroaryl methyl beta piperidino propanoic acid compounds as orl1-receptor antagonists |
| DE102004039382A1 (de) * | 2004-08-13 | 2006-02-23 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| JP2008542375A (ja) * | 2005-06-02 | 2008-11-27 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Ｏｒｌ−１受容体モジュレーターとして有用な新規３−スピロ環式インドリル誘導体 |
-
2010
- 2010-11-12 DK DK10782486.4T patent/DK2501704T3/da active
- 2010-11-12 EP EP10782486.4A patent/EP2501704B1/en active Active
- 2010-11-12 KR KR1020127012503A patent/KR101368130B1/ko not_active Expired - Fee Related
- 2010-11-12 PT PT107824864T patent/PT2501704E/pt unknown
- 2010-11-12 WO PCT/US2010/056449 patent/WO2011060217A1/en not_active Ceased
- 2010-11-12 US US13/504,176 patent/US20120214784A1/en not_active Abandoned
- 2010-11-12 HR HRP20130969AT patent/HRP20130969T1/hr unknown
- 2010-11-12 BR BR112012011710A patent/BR112012011710A2/pt active Search and Examination
- 2010-11-12 CA CA2781041A patent/CA2781041C/en not_active Expired - Fee Related
- 2010-11-12 ES ES10782486T patent/ES2436241T3/es active Active
- 2010-11-12 MX MX2012005690A patent/MX2012005690A/es active IP Right Grant
- 2010-11-12 CN CN201080051845.3A patent/CN102666550B/zh not_active Expired - Fee Related
- 2010-11-12 AU AU2010319400A patent/AU2010319400B2/en not_active Ceased
- 2010-11-12 EA EA201290355A patent/EA020391B1/ru not_active IP Right Cessation
- 2010-11-12 SI SI201030389T patent/SI2501704T1/sl unknown
- 2010-11-12 JP JP2012538997A patent/JP5723381B2/ja active Active
- 2010-11-12 PL PL10782486T patent/PL2501704T3/pl unknown
- 2010-11-12 RS RS20130484A patent/RS53017B/sr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2781041C (en) | 2015-01-06 |
| US20120214784A1 (en) | 2012-08-23 |
| WO2011060217A1 (en) | 2011-05-19 |
| MX2012005690A (es) | 2012-06-13 |
| CA2781041A1 (en) | 2011-05-19 |
| EP2501704B1 (en) | 2013-09-18 |
| BR112012011710A2 (pt) | 2016-03-01 |
| RS53017B (sr) | 2014-04-30 |
| AU2010319400B2 (en) | 2013-12-19 |
| CN102666550A (zh) | 2012-09-12 |
| PT2501704E (pt) | 2013-12-05 |
| AU2010319400A1 (en) | 2012-06-07 |
| EP2501704A1 (en) | 2012-09-26 |
| HRP20130969T1 (hr) | 2013-11-22 |
| JP5723381B2 (ja) | 2015-05-27 |
| CN102666550B (zh) | 2015-07-15 |
| EA020391B1 (ru) | 2014-10-30 |
| SI2501704T1 (sl) | 2013-11-29 |
| JP2013510870A (ja) | 2013-03-28 |
| PL2501704T3 (pl) | 2014-02-28 |
| DK2501704T3 (da) | 2013-10-14 |
| KR101368130B1 (ko) | 2014-02-27 |
| EA201290355A1 (ru) | 2012-10-30 |
| KR20120082927A (ko) | 2012-07-24 |
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