JP2015523406A5 - - Google Patents
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- Publication number
- JP2015523406A5 JP2015523406A5 JP2015524750A JP2015524750A JP2015523406A5 JP 2015523406 A5 JP2015523406 A5 JP 2015523406A5 JP 2015524750 A JP2015524750 A JP 2015524750A JP 2015524750 A JP2015524750 A JP 2015524750A JP 2015523406 A5 JP2015523406 A5 JP 2015523406A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- group
- cycloalkyl
- heterocyclyl
- halogen
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims 32
- 229910052736 halogen Inorganic materials 0.000 claims 15
- 125000000623 heterocyclic group Chemical group 0.000 claims 15
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 14
- 150000003839 salts Chemical class 0.000 claims 14
- 239000012453 solvate Substances 0.000 claims 14
- 125000001424 substituent group Chemical group 0.000 claims 14
- 150000002367 halogens Chemical class 0.000 claims 13
- 150000004677 hydrates Chemical class 0.000 claims 13
- 125000001153 fluoro group Chemical group F* 0.000 claims 10
- 206010012289 Dementia Diseases 0.000 claims 9
- 125000005843 halogen group Chemical group 0.000 claims 9
- 125000001072 heteroaryl group Chemical group 0.000 claims 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 5
- 230000003542 behavioural effect Effects 0.000 claims 4
- 208000035475 disorder Diseases 0.000 claims 4
- 125000004076 pyridyl group Chemical group 0.000 claims 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 3
- 230000007850 degeneration Effects 0.000 claims 3
- 230000004064 dysfunction Effects 0.000 claims 3
- 229910052731 fluorine Inorganic materials 0.000 claims 3
- 239000011737 fluorine Substances 0.000 claims 3
- 230000002265 prevention Effects 0.000 claims 3
- 208000011580 syndromic disease Diseases 0.000 claims 3
- 208000035976 Developmental Disabilities Diseases 0.000 claims 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 2
- 125000004452 carbocyclyl group Chemical group 0.000 claims 2
- 208000010877 cognitive disease Diseases 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 206010015037 epilepsy Diseases 0.000 claims 2
- 230000003340 mental effect Effects 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 208000000044 Amnesia Diseases 0.000 claims 1
- 208000019901 Anxiety disease Diseases 0.000 claims 1
- 206010003591 Ataxia Diseases 0.000 claims 1
- 206010003694 Atrophy Diseases 0.000 claims 1
- 208000020925 Bipolar disease Diseases 0.000 claims 1
- 208000028698 Cognitive impairment Diseases 0.000 claims 1
- 208000032928 Dyslipidaemia Diseases 0.000 claims 1
- 208000002705 Glucose Intolerance Diseases 0.000 claims 1
- 208000023105 Huntington disease Diseases 0.000 claims 1
- 208000009829 Lewy Body Disease Diseases 0.000 claims 1
- 201000002832 Lewy body dementia Diseases 0.000 claims 1
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 1
- 208000026139 Memory disease Diseases 0.000 claims 1
- 208000036626 Mental retardation Diseases 0.000 claims 1
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 1
- 208000019022 Mood disease Diseases 0.000 claims 1
- 208000019430 Motor disease Diseases 0.000 claims 1
- 208000027626 Neurocognitive disease Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 206010033799 Paralysis Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 208000020114 Schizophrenia and other psychotic disease Diseases 0.000 claims 1
- 201000001880 Sexual dysfunction Diseases 0.000 claims 1
- 208000027520 Somatoform disease Diseases 0.000 claims 1
- 201000004810 Vascular dementia Diseases 0.000 claims 1
- 201000008485 Wernicke-Korsakoff syndrome Diseases 0.000 claims 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 230000037444 atrophy Effects 0.000 claims 1
- 208000029560 autism spectrum disease Diseases 0.000 claims 1
- 210000004227 basal ganglia Anatomy 0.000 claims 1
- 208000018300 basal ganglia disease Diseases 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 210000003169 central nervous system Anatomy 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 230000019771 cognition Effects 0.000 claims 1
- 230000007278 cognition impairment Effects 0.000 claims 1
- 230000001054 cortical effect Effects 0.000 claims 1
- -1 cyclopropyl- Chemical group 0.000 claims 1
- 230000006735 deficit Effects 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 230000002996 emotional effect Effects 0.000 claims 1
- 210000001652 frontal lobe Anatomy 0.000 claims 1
- 210000002216 heart Anatomy 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 230000036571 hydration Effects 0.000 claims 1
- 238000006703 hydration reaction Methods 0.000 claims 1
- 208000013403 hyperactivity Diseases 0.000 claims 1
- 201000001421 hyperglycemia Diseases 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 230000006984 memory degeneration Effects 0.000 claims 1
- 206010027175 memory impairment Diseases 0.000 claims 1
- 208000023060 memory loss Diseases 0.000 claims 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims 1
- 230000036651 mood Effects 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 208000027753 pain disease Diseases 0.000 claims 1
- 230000008447 perception Effects 0.000 claims 1
- 230000035479 physiological effects, processes and functions Effects 0.000 claims 1
- 201000009104 prediabetes syndrome Diseases 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- 125000003373 pyrazinyl group Chemical group 0.000 claims 1
- 125000002098 pyridazinyl group Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 201000000980 schizophrenia Diseases 0.000 claims 1
- 231100000872 sexual dysfunction Toxicity 0.000 claims 1
- 230000001568 sexual effect Effects 0.000 claims 1
- 210000002027 skeletal muscle Anatomy 0.000 claims 1
- 210000003625 skull Anatomy 0.000 claims 1
- 208000019116 sleep disease Diseases 0.000 claims 1
- 208000020685 sleep-wake disease Diseases 0.000 claims 1
- 210000000813 small intestine Anatomy 0.000 claims 1
- 210000000952 spleen Anatomy 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 230000009885 systemic effect Effects 0.000 claims 1
- 210000001550 testis Anatomy 0.000 claims 1
- 230000000542 thalamic effect Effects 0.000 claims 1
- 210000001541 thymus gland Anatomy 0.000 claims 1
- 230000008733 trauma Effects 0.000 claims 1
- 208000018726 traumatic encephalopathy Diseases 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12178713 | 2012-07-31 | ||
| EP12178713.9 | 2012-07-31 | ||
| PCT/EP2013/065894 WO2014019979A1 (en) | 2012-07-31 | 2013-07-29 | 4-methyl-2,3,5,9,9b-pentaaza-cyclopenta[a]naphthalenes |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015523406A JP2015523406A (ja) | 2015-08-13 |
| JP2015523406A5 true JP2015523406A5 (enExample) | 2016-09-15 |
| JP6356671B2 JP6356671B2 (ja) | 2018-07-11 |
Family
ID=48906250
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015524750A Active JP6356671B2 (ja) | 2012-07-31 | 2013-07-29 | ４−メチル−２，３，５，９，９ｂ−ペンタアザ−シクロペンタ［ａ］ナフタレン |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US20140045856A1 (enExample) |
| EP (1) | EP2882749B1 (enExample) |
| JP (1) | JP6356671B2 (enExample) |
| KR (1) | KR20150037950A (enExample) |
| CN (1) | CN104428302B (enExample) |
| AP (1) | AP2015008202A0 (enExample) |
| AR (1) | AR091939A1 (enExample) |
| AU (1) | AU2013298621B2 (enExample) |
| BR (1) | BR112015002118A2 (enExample) |
| CA (1) | CA2880447A1 (enExample) |
| CL (1) | CL2015000096A1 (enExample) |
| CO (1) | CO7310531A2 (enExample) |
| EA (1) | EA028958B1 (enExample) |
| EC (1) | ECSP15006871A (enExample) |
| GE (1) | GEP201706707B (enExample) |
| IL (1) | IL236494A0 (enExample) |
| MA (1) | MA37798B1 (enExample) |
| MX (1) | MX2015000965A (enExample) |
| NZ (1) | NZ703797A (enExample) |
| PE (1) | PE20150706A1 (enExample) |
| PH (1) | PH12015500211B1 (enExample) |
| SG (1) | SG11201500772VA (enExample) |
| TN (1) | TN2015000022A1 (enExample) |
| TW (1) | TW201418255A (enExample) |
| UA (1) | UA115561C2 (enExample) |
| UY (1) | UY34955A (enExample) |
| WO (1) | WO2014019979A1 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9540379B2 (en) | 2011-01-31 | 2017-01-10 | Boehringer Ingelheim International Gmbh | (1,2,4)triazolo[4,3-A]quinoxaline derivatives as inhibitors of phosphodiesterases |
| JP2014526453A (ja) * | 2011-09-09 | 2014-10-06 | ハー・ルンドベック・アクチエゼルスカベット | ピリジン化合物およびそれらの使用 |
| US20140045856A1 (en) * | 2012-07-31 | 2014-02-13 | Boehringer Ingelheim International Gmbh | 4-Methyl-2,3,5,9,9b-pentaaza-cyclopenta[a]naphthalenes |
| WO2016145614A1 (en) | 2015-03-17 | 2016-09-22 | Merck Sharp & Dohme Corp. | Triazolyl pyrimidinone compounds as pde2 inhibitors |
| WO2016154081A1 (en) | 2015-03-26 | 2016-09-29 | Merck Sharp & Dohme Corp. | Pyrazolyl pyrimidinone compounds as pde2 inhibitors |
| US10195201B2 (en) | 2015-05-05 | 2019-02-05 | Merck Sharp & Dohme Corp. | Heteroaryl-pyrimidinone compounds as PDE2 inhibitors |
| WO2016183741A1 (en) | 2015-05-15 | 2016-11-24 | Merck Sharp & Dohme Corp. | Pyrimidinone amide compounds as pde2 inhibitors |
| US10618898B2 (en) * | 2015-05-20 | 2020-04-14 | Guangdong Raynovent Biotech Co., Ltd. | Hydroxyl purine compounds and use thereof |
| WO2016191935A1 (en) | 2015-05-29 | 2016-12-08 | Merck Sharp & Dohme Corp. | 6-alkyl dihydropyrazolopyrimidinone compounds as pde2 inhibitors |
| WO2016192083A1 (en) | 2015-06-04 | 2016-12-08 | Merck Sharp & Dohme Corp. | Dihydropyrazolopyrimidinone compounds as pde2 inhibitors |
| US10647727B2 (en) | 2015-06-25 | 2020-05-12 | Merck Sharp & Dohme Corp. | Substituted pyrazolo/imidazolo bicyclic compounds as PDE2 inhibitors |
| WO2017000277A1 (en) | 2015-07-01 | 2017-01-05 | Merck Sharp & Dohme Corp. | Substituted triazolo bicycliccompounds as pde2 inhibitors |
| WO2017000276A1 (en) | 2015-07-01 | 2017-01-05 | Merck Sharp & Dohme Corp. | Bicyclic heterocyclic compounds as pde2 inhibitors |
| EP3156405A1 (en) | 2015-10-13 | 2017-04-19 | Boehringer Ingelheim International GmbH | Spirocyclic ether derivatives of pyrazolo[1,5-a]pyrimidine-3-carboxamide |
| WO2017176652A2 (en) | 2016-04-04 | 2017-10-12 | Sinopia Biosciences, Inc. | Treating extrapyramidal syndrome using trapidil |
| AR112457A1 (es) * | 2017-08-02 | 2019-10-30 | Lilly Co Eli | Derivados de [1,2,4]triazolo[4,3-a]pirazin-6(5h)-ona |
| PT3713572T (pt) | 2017-11-23 | 2025-08-28 | Oslo Univ Hospital Hf | Tratamento da taquicardia |
| CN115916180A (zh) | 2020-03-26 | 2023-04-04 | 希诺皮亚生物科学公司 | 同位素标记的曲匹地尔衍生物 |
| CN115960101B (zh) * | 2022-12-30 | 2024-10-18 | 海南大学 | 7-氧代-4,5,6,7-四氢吡唑并吡啶酰胺类化合物及其制备方法和应用 |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000319277A (ja) * | 1999-05-11 | 2000-11-21 | Ono Pharmaceut Co Ltd | 縮合ピラジン化合物およびその化合物を有効成分とする薬剤 |
| JP2000319278A (ja) * | 1999-05-11 | 2000-11-21 | Ono Pharmaceut Co Ltd | 縮合ピラジン化合物およびその化合物を有効成分とする薬剤 |
| DE10108752A1 (de) | 2001-02-23 | 2002-09-05 | Bayer Ag | Neue Substituierte Imidazotriazinone |
| CA2520251A1 (en) | 2003-03-27 | 2004-10-07 | Pfizer Products Inc. | Substituted 4-amino[1,2,4]triazolo[4,3-a]quinoxalines |
| WO2005041957A1 (en) | 2003-10-29 | 2005-05-12 | Pfizer Products Inc. | Oxindole derivatives and their use as phosphodiesterase type 2 inhibitors |
| GEP20094720B (en) | 2003-12-16 | 2009-06-25 | Pfizer Prod Inc | Pyrido[2,3-d]pyrimidine-2,4-diamines as pde 2 inhibitors |
| EP1548011A1 (en) | 2003-12-23 | 2005-06-29 | Neuro3D | Benzo[1,4]diazepin-2-one derivatives as phosphodiesterase PDE2 inhibitors, preparation and therapeutic use thereof |
| FR2865331A1 (fr) | 2004-01-21 | 2005-07-22 | France Telecom | Procede de connexion d'un reseau domestique a un serveur cops distant et dispositif associe |
| FR2870539B1 (fr) | 2004-05-19 | 2006-08-04 | Greenpharma Sa Sa | Nouvelles methodes et medicaments |
| BRPI0514586A (pt) | 2004-09-02 | 2008-06-17 | Altana Pharma Ag | triazolftalazinas |
| CA2591991C (en) | 2005-01-05 | 2013-11-19 | Altana Pharma Ag | Triazolophthalazines |
| MX2007008137A (es) | 2005-01-05 | 2007-07-19 | Altana Pharma Ag | Triazoloftalazinas como inhibidores de pde2. |
| BRPI0502411A (pt) | 2005-03-31 | 2006-11-28 | Univ Minas Gerais | processo de desenvolvimento de substáncias como inibidores potentes e seletivos de isoformas de fosfodiesterases dos tipos 1 a 5 (pde1,pde2,pde3, pde4, pde5) na base de diocleìna, fluranol ou análogos e suas composições farmacêuticas para o estudo e tratamento de doenças cardiovasculares e produtos associados |
| WO2007087250A2 (en) | 2006-01-23 | 2007-08-02 | Amira Pharmaceuticals, Inc. | Tricyclic inhibitors of 5-lipoxygenase |
| WO2007121319A2 (en) | 2006-04-14 | 2007-10-25 | University Of California | Compostions and methods for determining and predicting treatment responses for depression and anxiety |
| TW200815436A (en) | 2006-05-30 | 2008-04-01 | Elbion Ag | 4-amino-pyrido[3,2-e]pyrazines, their use as inhibitors of phosphodiesterase 10, and processes for preparing them |
| TW200817400A (en) * | 2006-05-30 | 2008-04-16 | Elbion Ag | Pyrido [3,2-e] pyrazines, their use as inhibitors of phosphodiesterase 10, and processes for preparing them |
| US20080090834A1 (en) | 2006-07-06 | 2008-04-17 | Pfizer Inc | Selective azole pde10a inhibitor compounds |
| DE102006048693A1 (de) | 2006-10-14 | 2008-04-17 | Bayer Healthcare Ag | Inhibition der PDE2A |
| WO2008072779A1 (ja) * | 2006-12-13 | 2008-06-19 | Aska Pharmaceutical Co., Ltd. | キノキサリン誘導体 |
| US20090143361A1 (en) * | 2007-11-30 | 2009-06-04 | Elbion Gmbh | Pyrido[3,2-E]Pyrazines, Process For Preparing The Same, And Their Use As Inhibitors Of Phosphodiesterase 10 |
| TWI501965B (zh) | 2008-06-20 | 2015-10-01 | Lundbeck & Co As H | 作為ｐｄｅ１０ａ酵素抑制劑之新穎苯基咪唑衍生物 |
| AU2009291719A1 (en) | 2008-09-10 | 2010-03-18 | Alcon Research, Ltd | Heterocyclic inhibitors of histamine receptors for the treatment of disease |
| CN102272135A (zh) | 2008-10-08 | 2011-12-07 | 百时美施贵宝公司 | 唑并吡咯酮黑色素浓集激素受体-1拮抗剂 |
| WO2010054253A1 (en) | 2008-11-07 | 2010-05-14 | Biotie Therapies Gmbh | Triazine derivatives as inhibitors of phosphodiesterases |
| WO2010104933A1 (en) * | 2009-03-11 | 2010-09-16 | Merck Sharp & Dohme Corp. | Inhibitors of akt activity |
| EP2266985A1 (en) * | 2009-06-26 | 2010-12-29 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Tricyclic Pyrimidine Derivatives as Wnt antagonists |
| CN107141309A (zh) * | 2011-01-11 | 2017-09-08 | 桑诺维恩药品公司 | 杂芳基化合物及其使用方法 |
| US9540379B2 (en) | 2011-01-31 | 2017-01-10 | Boehringer Ingelheim International Gmbh | (1,2,4)triazolo[4,3-A]quinoxaline derivatives as inhibitors of phosphodiesterases |
| BR112013033375B1 (pt) | 2011-06-27 | 2022-05-10 | Janssen Pharmaceutica N.V | Derivados de 1-aril-4-metil-[1,2,4]triazolo[4,3-a]quinoxa-lina, seu uso, composição farmacêutica que os compreende, processo de preparação dos mesmos, solução estéril e composto intermediário |
| WO2013034758A1 (en) | 2011-09-09 | 2013-03-14 | H. Lundbeck A/S | Substituted triazolopyrazines and uses thereof |
| JP2014526453A (ja) | 2011-09-09 | 2014-10-06 | ハー・ルンドベック・アクチエゼルスカベット | ピリジン化合物およびそれらの使用 |
| AR088082A1 (es) | 2011-10-13 | 2014-05-07 | Lilly Co Eli | Moduladores selectivos del receptor androgeno |
| RU2657540C2 (ru) | 2012-06-26 | 2018-06-14 | Янссен Фармацевтика Нв | Комбинации, содержащие ингибиторы pde 2, такие как 1-арил-4-метил-[1,2,4]триазоло[4,3-а]хиноксалиновые соединения, и ингибиторы pde 10, для применения в лечении неврологических или метаболических расстройств |
| US20140045856A1 (en) * | 2012-07-31 | 2014-02-13 | Boehringer Ingelheim International Gmbh | 4-Methyl-2,3,5,9,9b-pentaaza-cyclopenta[a]naphthalenes |
-
2013
- 2013-07-18 US US13/945,008 patent/US20140045856A1/en not_active Abandoned
- 2013-07-26 US US13/951,531 patent/US9085584B2/en active Active
- 2013-07-29 PE PE2015000102A patent/PE20150706A1/es not_active Application Discontinuation
- 2013-07-29 WO PCT/EP2013/065894 patent/WO2014019979A1/en not_active Ceased
- 2013-07-29 CA CA2880447A patent/CA2880447A1/en not_active Abandoned
- 2013-07-29 EA EA201500182A patent/EA028958B1/ru not_active IP Right Cessation
- 2013-07-29 NZ NZ703797A patent/NZ703797A/en not_active IP Right Cessation
- 2013-07-29 JP JP2015524750A patent/JP6356671B2/ja active Active
- 2013-07-29 EP EP13742632.6A patent/EP2882749B1/en active Active
- 2013-07-29 AU AU2013298621A patent/AU2013298621B2/en not_active Ceased
- 2013-07-29 MA MA37798A patent/MA37798B1/fr unknown
- 2013-07-29 AP AP2015008202A patent/AP2015008202A0/xx unknown
- 2013-07-29 UA UAA201501673A patent/UA115561C2/uk unknown
- 2013-07-29 CN CN201380037349.6A patent/CN104428302B/zh not_active Expired - Fee Related
- 2013-07-29 SG SG11201500772VA patent/SG11201500772VA/en unknown
- 2013-07-29 MX MX2015000965A patent/MX2015000965A/es unknown
- 2013-07-29 BR BR112015002118A patent/BR112015002118A2/pt not_active IP Right Cessation
- 2013-07-29 GE GEAP201313748A patent/GEP201706707B/en unknown
- 2013-07-29 KR KR20157002607A patent/KR20150037950A/ko not_active Withdrawn
- 2013-07-30 AR ARP130102708A patent/AR091939A1/es unknown
- 2013-07-30 TW TW102127314A patent/TW201418255A/zh unknown
- 2013-07-31 UY UY0001034955A patent/UY34955A/es unknown
-
2014
- 2014-12-28 IL IL236494A patent/IL236494A0/en unknown
-
2015
- 2015-01-14 CL CL2015000096A patent/CL2015000096A1/es unknown
- 2015-01-16 TN TNP2015000022A patent/TN2015000022A1/fr unknown
- 2015-01-29 CO CO15018184A patent/CO7310531A2/es unknown
- 2015-01-30 PH PH12015500211A patent/PH12015500211B1/en unknown
- 2015-02-25 EC ECIEPI20156871A patent/ECSP15006871A/es unknown
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