ECSP13013068A - Halogenoalquil-1,3-oxazinas como inhibidores de la bace1 y/o bace2 - Google Patents
Halogenoalquil-1,3-oxazinas como inhibidores de la bace1 y/o bace2Info
- Publication number
- ECSP13013068A ECSP13013068A ECSP13013068A ECSP13013068A EC SP13013068 A ECSP13013068 A EC SP13013068A EC SP13013068 A ECSP13013068 A EC SP13013068A EC SP13013068 A ECSP13013068 A EC SP13013068A
- Authority
- EC
- Ecuador
- Prior art keywords
- bace2
- bace1
- oxazinas
- halogenoalquil
- inhibitors
- Prior art date
Links
- 102100021257 Beta-secretase 1 Human genes 0.000 title abstract 2
- 102100021277 Beta-secretase 2 Human genes 0.000 title abstract 2
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 title abstract 2
- 101000894883 Homo sapiens Beta-secretase 2 Proteins 0.000 title abstract 2
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 2
- 208000024827 Alzheimer disease Diseases 0.000 abstract 1
- 239000013543 active substance Substances 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 238000011321 prophylaxis Methods 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract 1
Classifications
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- 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
- C07D413/12—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 chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
- A61P5/16—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4 for decreasing, blocking or antagonising the activity of the thyroid hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Endocrinology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Transplantation (AREA)
- Reproductive Health (AREA)
- Psychology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
La presente invención proporciona compuestos de la fórmula I:que tienen actividad inhibidora de la BACE1 y/o de la BACE2, su obtención, composiciones farmacéuticas que los contienen y su utilización como sustancias terapéuticamente activas. Los compuestos activos de la presente invención son útiles para el tratamiento terapéutico y/o profiláctico p.ej. de la enfermedad de Alzheimer y de la diabetes de tipo 2.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11169007 | 2011-06-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ECSP13013068A true ECSP13013068A (es) | 2014-01-31 |
Family
ID=46208521
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ECSP13013068 ECSP13013068A (es) | 2011-06-07 | 2013-12-04 | Halogenoalquil-1,3-oxazinas como inhibidores de la bace1 y/o bace2 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US8987255B2 (es) |
| EP (1) | EP2718286A1 (es) |
| JP (1) | JP2014516063A (es) |
| KR (1) | KR20140041687A (es) |
| CN (1) | CN103717592A (es) |
| AU (1) | AU2012266544A1 (es) |
| BR (1) | BR112013031098A2 (es) |
| CA (1) | CA2837252A1 (es) |
| CL (1) | CL2013003472A1 (es) |
| CO (1) | CO6811854A2 (es) |
| CR (1) | CR20130588A (es) |
| EA (1) | EA023261B1 (es) |
| EC (1) | ECSP13013068A (es) |
| IL (1) | IL229686A0 (es) |
| MA (1) | MA35193B1 (es) |
| MX (1) | MX2013013692A (es) |
| PE (1) | PE20140623A1 (es) |
| PH (1) | PH12013502316A1 (es) |
| WO (1) | WO2012168164A1 (es) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2628074C (en) | 2005-10-25 | 2014-01-14 | Shionogi & Co., Ltd. | Aminodihydrothiazine derivative |
| JP5383484B2 (ja) | 2007-04-24 | 2014-01-08 | 塩野義製薬株式会社 | 環式基で置換されたアミノジヒドロチアジン誘導体 |
| US8653067B2 (en) | 2007-04-24 | 2014-02-18 | Shionogi & Co., Ltd. | Pharmaceutical composition for treating Alzheimer's disease |
| KR101324426B1 (ko) | 2008-06-13 | 2013-10-31 | 시오노기세야쿠 가부시키가이샤 | β 세크레타제 저해 작용을 갖는 황 함유 복소환 유도체 |
| CN102186841A (zh) | 2008-10-22 | 2011-09-14 | 盐野义制药株式会社 | 具有bace1抑制活性的2-氨基嘧啶-4-酮及2-氨基吡啶衍生物 |
| WO2011044187A1 (en) | 2009-10-08 | 2011-04-14 | Schering Corporation | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| EP2485920B1 (en) | 2009-10-08 | 2016-04-27 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use |
| MX2012006491A (es) | 2009-12-11 | 2012-07-03 | Shionogi & Co | Derivados de oxazina. |
| JP5816630B2 (ja) | 2010-10-29 | 2015-11-18 | 塩野義製薬株式会社 | ナフチリジン誘導体 |
| EP2634188A4 (en) | 2010-10-29 | 2014-05-07 | Shionogi & Co | FUSIONED AMINODIHYDROPYRIMIDINE DERIVATIVE |
| US8883779B2 (en) | 2011-04-26 | 2014-11-11 | Shinogi & Co., Ltd. | Oxazine derivatives and a pharmaceutical composition for inhibiting BACE1 containing them |
| CN103717592A (zh) * | 2011-06-07 | 2014-04-09 | 霍夫曼-拉罗奇有限公司 | 作为bace1和/或bace2抑制剂的卤代-烷基-1,3噁嗪类 |
| UY34278A (es) | 2011-08-25 | 2013-04-05 | Novartis Ag | Derivados novedosos de oxazina y su uso en el tratamiento de enfermedades |
| EP2912035A4 (en) | 2012-10-24 | 2016-06-15 | Shionogi & Co | DERIVATIVES OF DIHYDROOXAZINE OR OXAZEPINE HAVING BACE1 INHIBITING ACTIVITY |
| CN104968660A (zh) * | 2013-01-22 | 2015-10-07 | 霍夫曼-拉罗奇有限公司 | 作为bace1抑制剂的氟-[1,3]噁嗪类化合物 |
| WO2014134341A1 (en) | 2013-03-01 | 2014-09-04 | Amgen Inc. | Perfluorinated 5,6-dihydro-4h-1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| MX374512B (es) | 2013-03-08 | 2025-03-06 | Amgen Inc | Compuestos de 1,3-oxazin-2-amina fusionados con ciclopropilo perfluorado como inhibidores de beta-secretasa y métodos de uso. |
| AU2014253275B2 (en) * | 2013-04-11 | 2018-10-18 | F. Hoffmann-La Roche Ag | BACE1 inhibitors |
| KR20160115936A (ko) | 2014-02-19 | 2016-10-06 | 하. 룬드벡 아크티에셀스카브 | 알츠하이머병의 치료를 위한 bace1 저해제로서의 2-아미노-3,5,5-트리플루오로-3,4,5,6-테트라하이드로피리딘 |
| TW201623295A (zh) | 2014-04-11 | 2016-07-01 | 塩野義製藥股份有限公司 | 具有bace1抑制活性之二氫噻及二氫衍生物 |
| WO2016001266A1 (en) | 2014-07-04 | 2016-01-07 | F. Hoffmann-La Roche Ag | Fluoro-[1,3]oxazines as bace1 inhibitors |
| CN106795147B (zh) | 2014-08-08 | 2020-09-22 | 美国安进公司 | 作为β-分泌酶抑制剂的环丙基稠合噻嗪-2-胺化合物和使用方法 |
| MA40941A (fr) * | 2014-11-10 | 2017-09-19 | H Lundbeck As | 2-amino-5,5-difluoro-6-(fluorométhyl)-6-phényl-3,4,5,6-tétrahydropyridines comme inhibiteurs de bace1 |
| CR20170187A (es) | 2014-11-10 | 2018-02-01 | H Lundbeck As | 2-Amino-3,5-difluoro-6-metil-6-fenil-3,4,5,6-tetrahidropiridinas en calidad de inhibidores de BACE1 para el tratamiento de la enfermedad de Alzheimer |
| JO3458B1 (ar) | 2014-11-10 | 2020-07-05 | H Lundbeck As | 2- أمينو-6- (دايفلوروميثيل) – 5، 5- ديفلورو-6-فينيل-3،4، 5، 6-تيتراهيدروبيريدين كمثبطات bace1 |
| EP3271355B1 (en) | 2015-03-20 | 2020-07-29 | H. Hoffnabb-La Roche Ag | Bace1 inhibitors |
| TW201717948A (zh) | 2015-08-10 | 2017-06-01 | H 朗德貝克公司 | 包括給予2-胺基-3,5,5-三氟-3,4,5,6-四氫吡啶的聯合治療 |
| EP3334720A1 (en) | 2015-08-12 | 2018-06-20 | H. Lundbeck A/S | 2-amino-3-fluoro-3-(fluoromethyl)-6-methyl-6-phenyl-3,4,5,6-tetrahydropyridins as bace1 inhibitors |
| AU2019258575A1 (en) | 2018-04-27 | 2020-10-29 | Shionogi & Co., Ltd. | Tetrahydropyranooxazine derivatives having selective BACE1 inhibitory activity |
| US12042492B2 (en) | 2020-10-09 | 2024-07-23 | Texas Tech University System | BACE1 inhibitory ligand molecules against amyloid beta-induced synaptic and mitochondrial toxicities |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998057925A1 (en) | 1997-06-16 | 1998-12-23 | American Home Products Corporation | Elevation of hdl cholesterol by 2-[(aminothioxomethyl)-hydrazono]-2-arylethyl carbamates |
| WO2005016876A2 (en) * | 2003-08-08 | 2005-02-24 | Schering Corporation | Cyclic amine bace-1 inhibitors having a benzamide substituent |
| AR045219A1 (es) * | 2003-08-08 | 2005-10-19 | Pharmacopeia Inc | Aminas ciclicas inhibidoras de base - 1 que poseen un sustiuyente heterociclico |
| BRPI0512213A (pt) * | 2004-06-16 | 2008-02-19 | Wyeth Corp | método para tratamento, prevenção ou melhora de uma doença ou distúrbio; composição farmacêutica; processo para a preparação de um composto; e uso de um composto |
| SV2006002232A (es) * | 2004-09-21 | 2006-05-25 | Lilly Co Eli | Inhibidores bace ref. x-16940 |
| TW200730523A (en) * | 2005-07-29 | 2007-08-16 | Wyeth Corp | Cycloalkyl amino-hydantoin compounds and use thereof for β-secretase modulation |
| CA2628074C (en) | 2005-10-25 | 2014-01-14 | Shionogi & Co., Ltd. | Aminodihydrothiazine derivative |
| JP5383484B2 (ja) | 2007-04-24 | 2014-01-08 | 塩野義製薬株式会社 | 環式基で置換されたアミノジヒドロチアジン誘導体 |
| UY32799A (es) * | 2009-07-24 | 2011-02-28 | Novartis Ag | Derivados de oxazina y su uso en el tratamiento de trastornos neurológicos |
| US8188079B2 (en) | 2009-08-19 | 2012-05-29 | Hoffman-La Roche Inc. | 3-amino-5-phenyl-5,6-dihydro-2H-[1,4]oxazines |
| US7964594B1 (en) * | 2009-12-10 | 2011-06-21 | Hoffmann-La Roche Inc. | Amino oxazine derivatives |
| UA103272C2 (uk) * | 2009-12-11 | 2013-09-25 | Ф. Хоффманн-Ля Рош Аг | 2-аміно-5,5-дифтор-5,6-дигідро-4h-оксазини як інгібітори bace1 і/або bace2 |
| MX2012006491A (es) * | 2009-12-11 | 2012-07-03 | Shionogi & Co | Derivados de oxazina. |
| MX339640B (es) | 2010-06-09 | 2016-06-01 | Janssen Pharmaceutica Nv * | Derivados de 5, 6-dihidro-2h-[1, 4] oxazin-3-il-amina utiles como inhibidores de la beta-secretasa (bace). |
| CN103052323B (zh) * | 2010-08-05 | 2015-09-30 | 雀巢产品技术援助有限公司 | 具有天然稳定剂的冷冻甜食产品 |
| JP2012250933A (ja) * | 2011-06-03 | 2012-12-20 | Shionogi & Co Ltd | オキサジン誘導体を含有するアルツハイマー症治療用または予防用医薬組成物 |
| CN103717592A (zh) * | 2011-06-07 | 2014-04-09 | 霍夫曼-拉罗奇有限公司 | 作为bace1和/或bace2抑制剂的卤代-烷基-1,3噁嗪类 |
-
2012
- 2012-06-04 CN CN201280027493.7A patent/CN103717592A/zh active Pending
- 2012-06-04 AU AU2012266544A patent/AU2012266544A1/en not_active Abandoned
- 2012-06-04 MX MX2013013692A patent/MX2013013692A/es not_active Application Discontinuation
- 2012-06-04 EA EA201391786A patent/EA023261B1/ru not_active IP Right Cessation
- 2012-06-04 PH PH1/2013/502316A patent/PH12013502316A1/en unknown
- 2012-06-04 JP JP2014514010A patent/JP2014516063A/ja active Pending
- 2012-06-04 PE PE2013002764A patent/PE20140623A1/es not_active Application Discontinuation
- 2012-06-04 WO PCT/EP2012/060457 patent/WO2012168164A1/en not_active Ceased
- 2012-06-04 US US14/116,043 patent/US8987255B2/en not_active Expired - Fee Related
- 2012-06-04 BR BR112013031098A patent/BR112013031098A2/pt not_active IP Right Cessation
- 2012-06-04 EP EP12725743.4A patent/EP2718286A1/en not_active Withdrawn
- 2012-06-04 KR KR1020147000274A patent/KR20140041687A/ko not_active Withdrawn
- 2012-06-04 CA CA2837252A patent/CA2837252A1/en not_active Abandoned
-
2013
- 2013-11-12 CR CR20130588A patent/CR20130588A/es unknown
- 2013-11-20 CO CO13273106A patent/CO6811854A2/es active IP Right Grant
- 2013-11-28 IL IL229686A patent/IL229686A0/en unknown
- 2013-12-04 CL CL2013003472A patent/CL2013003472A1/es unknown
- 2013-12-04 EC ECSP13013068 patent/ECSP13013068A/es unknown
- 2013-12-18 MA MA36584A patent/MA35193B1/fr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PH12013502316A1 (en) | 2015-09-04 |
| US20140080819A1 (en) | 2014-03-20 |
| MA35193B1 (fr) | 2014-06-02 |
| CO6811854A2 (es) | 2013-12-16 |
| AU2012266544A1 (en) | 2013-11-21 |
| CN103717592A (zh) | 2014-04-09 |
| MX2013013692A (es) | 2014-03-05 |
| KR20140041687A (ko) | 2014-04-04 |
| CA2837252A1 (en) | 2012-12-13 |
| CR20130588A (es) | 2014-02-18 |
| EA201391786A1 (ru) | 2014-04-30 |
| PE20140623A1 (es) | 2014-05-30 |
| IL229686A0 (en) | 2014-01-30 |
| JP2014516063A (ja) | 2014-07-07 |
| WO2012168164A1 (en) | 2012-12-13 |
| EP2718286A1 (en) | 2014-04-16 |
| BR112013031098A2 (pt) | 2016-12-06 |
| EA023261B1 (ru) | 2016-05-31 |
| US8987255B2 (en) | 2015-03-24 |
| NZ617507A (en) | 2015-07-31 |
| CL2013003472A1 (es) | 2014-08-18 |
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