MX2012007273A - Pteridinonas como inhibidores de la quinasa tipo polo. - Google Patents
Pteridinonas como inhibidores de la quinasa tipo polo.Info
- Publication number
- MX2012007273A MX2012007273A MX2012007273A MX2012007273A MX2012007273A MX 2012007273 A MX2012007273 A MX 2012007273A MX 2012007273 A MX2012007273 A MX 2012007273A MX 2012007273 A MX2012007273 A MX 2012007273A MX 2012007273 A MX2012007273 A MX 2012007273A
- Authority
- MX
- Mexico
- Prior art keywords
- pteridinones
- polo
- kinase
- inhibitors
- compounds
- Prior art date
Links
- VWXIHLCLIOQWRA-UHFFFAOYSA-N 1h-pteridin-2-one Chemical class N1=CC=NC2=NC(O)=NC=C21 VWXIHLCLIOQWRA-UHFFFAOYSA-N 0.000 title 1
- 101000582926 Dictyostelium discoideum Probable serine/threonine-protein kinase PLK Proteins 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 3
- 208000018737 Parkinson disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
- C07D475/04—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/12—Heterocyclic compounds containing pteridine ring systems containing pteridine ring systems condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed 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
- C07D498/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
La presente invención provee compuestos que tienen una estructura de acuerdo con la Fórmula (I) o una sal o solvato de la misma, en donde el anillo A, X, R1, R2, R3, R4, R5 y R6, son definidos en la presente. La invención provee además composiciones farmacéuticas que incluyen los compuestos de la invención y métodos para formar y usar los compuestos y composiciones de la invención, v.gr., en el tratamiento y prevención de varios trastornos, tales como enfermedad de Parkinson.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28998009P | 2009-12-23 | 2009-12-23 | |
| US40479710P | 2010-10-08 | 2010-10-08 | |
| PCT/US2010/061535 WO2011079114A1 (en) | 2009-12-23 | 2010-12-21 | Pteridinones as inhibitors of polo - like kinase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2012007273A true MX2012007273A (es) | 2012-12-17 |
Family
ID=43530443
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2012007273A MX2012007273A (es) | 2009-12-23 | 2010-12-21 | Pteridinonas como inhibidores de la quinasa tipo polo. |
Country Status (15)
| Country | Link |
|---|---|
| US (5) | US8445503B2 (es) |
| EP (1) | EP2516441B1 (es) |
| JP (1) | JP2013515734A (es) |
| KR (1) | KR20120120252A (es) |
| CN (1) | CN102762568A (es) |
| AU (1) | AU2010336509A1 (es) |
| BR (1) | BR112012015714A2 (es) |
| CA (1) | CA2783258A1 (es) |
| IL (1) | IL220563A0 (es) |
| MX (1) | MX2012007273A (es) |
| PH (1) | PH12012501122A1 (es) |
| RU (1) | RU2012131124A (es) |
| SG (1) | SG181908A1 (es) |
| WO (2) | WO2011079114A1 (es) |
| ZA (1) | ZA201204136B (es) |
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| EP2992878A1 (en) * | 2010-02-03 | 2016-03-09 | Signal Pharmaceuticals, LLC | Identification of lkb1 mutation as a predictive biomarker for sensitivity to tor kinase inhibitors |
| RU2014118677A (ru) | 2010-10-08 | 2015-11-20 | Элан Фармасьютикалз, Инк. | Ингибиторы киназ типа polo |
| AR085406A1 (es) * | 2011-02-25 | 2013-09-25 | Takeda Pharmaceutical | Oxazinopteridinas y oxazinopteridinonas n-sustituidas |
| EP2830620A4 (en) * | 2012-03-26 | 2015-12-09 | Univ Columbia | 4-AMINOPYRIDINE AS A THERAPEUTIC AGENT FOR SPINAL MUSCLE ATROPHY |
| AU2013326867B2 (en) * | 2012-10-05 | 2018-03-08 | Rigel Pharmaceuticals, Inc. | GDF-8 inhibitors |
| AU2013203714B2 (en) | 2012-10-18 | 2015-12-03 | Signal Pharmaceuticals, Llc | Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity |
| EP2958919B1 (en) * | 2013-02-21 | 2019-05-22 | Boehringer Ingelheim International GmbH | Dihydropteridinones i |
| CA2909579A1 (en) | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Combination therapy comprising a tor kinase inhibitor and n-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide for treating cancer |
| JP6382945B2 (ja) | 2013-04-17 | 2018-08-29 | シグナル ファーマシューティカルズ,エルエルシー | ジヒドロピラジノ−ピラジンによる癌治療 |
| WO2014172432A1 (en) | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Combination therapy comprising a tor kinase inhibitor and a cytidine analog for treating cancer |
| TWI654979B (zh) | 2013-04-17 | 2019-04-01 | 美商標誌製藥公司 | 使用tor激酶抑制劑組合療法以治療癌症之方法 |
| KR102221029B1 (ko) | 2013-04-17 | 2021-02-26 | 시그날 파마소티칼 엘엘씨 | 디하이드로피라지노-피라진을 사용한 암의 치료 |
| KR102459285B1 (ko) | 2013-04-17 | 2022-10-27 | 시그날 파마소티칼 엘엘씨 | 1-에틸-7-(2-메틸-6-(1H-1,2,4-트리아졸-3-일)피리딘-3-일)-3,4-디하이드로피라지노[2,3-b]피라진-2(1H)-온에 관한 약학 제제, 제조방법, 고체 형태 및 사용 방법 |
| WO2014172431A1 (en) | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Combination therapy comprising a dihydropyrazino-pyrazine compound and an androgen receptor antagonist for treating prostate cancer |
| CN113831345A (zh) | 2013-05-29 | 2021-12-24 | 西格诺药品有限公司 | 二氢吡嗪并吡嗪化合物的药物组合物、其固体形式和它们的用途 |
| CN103819400B (zh) * | 2013-09-16 | 2016-05-04 | 江西师范大学 | 一种多组分反应合成具有不对称结构1.4-二氢吡啶及其衍生物的方法 |
| RU2550346C2 (ru) * | 2013-09-26 | 2015-05-10 | Общество с ограниченной ответственностью "Отечественные Фармацевтические Технологии" ООО"ФармТех" | Новые химические соединения (варианты) и их применение для лечения онкологических заболеваний |
| NZ714742A (en) | 2014-04-16 | 2017-04-28 | Signal Pharm Llc | Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use |
| EP3131551A4 (en) | 2014-04-16 | 2017-09-20 | Signal Pharmaceuticals, LLC | SOLID FORMS COMPRISING 1-ETHYL-7-(2-METHYL-6-(1H-1,2,4-TRIAZOL-3-YL) PYRIDIN-3-YL)-3,4-DIHYDROPYRAZINO(2,3-b)PYRAZIN-2(1H)-ONE, AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF |
| CN104402823B (zh) * | 2014-11-05 | 2016-03-23 | 上海浩登材料科技有限公司 | 一种1,2-二甲基咪唑的制备方法 |
| CN104496906B (zh) * | 2014-11-05 | 2016-03-23 | 上海浩登材料科技有限公司 | 一种咪唑的制备方法 |
| WO2017002089A1 (en) | 2015-07-02 | 2017-01-05 | Wockhardt Limited | Nitrogen containing bicyclic compounds and their use in treatment of bacterial infections |
| KR101796779B1 (ko) | 2015-12-22 | 2017-11-10 | 한국화학연구원 | 다이하이드로프테리딘-온 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 포함하는 pi3 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물 |
| JOP20170169A1 (ar) | 2016-08-29 | 2019-01-30 | Novartis Ag | مركبات بيريدازين ثلاثية الحلقة مندمجة تفيد في علاج العدوى بفيروس أورثوميكسو |
| US10138222B2 (en) * | 2016-09-15 | 2018-11-27 | Boehringer Ingelheim International Gmbh | Substituted benzamides as RIPK2 inhibitors |
| CN106543185B (zh) * | 2016-11-10 | 2017-12-15 | 吉林大学 | 一种靶向泛素化降解plk1和brd4蛋白的化合物及其应用 |
| SG11201912403SA (en) | 2017-06-22 | 2020-01-30 | Celgene Corp | Treatment of hepatocellular carcinoma characterized by hepatitis b virus infection |
| PL3759113T3 (pl) | 2018-02-28 | 2025-01-20 | Novartis Ag | Pochodne 10-(di(fenylo)metylo)-4-hydroksy-8,9,9a,10-tetrahydro-7h- pirolo[1’,2’:4,5]pirazyno[1,2-b]pirydazyno-3,5-dionowe i związki pokrewne jako inhibitory replikacji ortomyksowirusów do leczenia grypy |
| CN108794493B (zh) * | 2018-04-28 | 2020-04-24 | 北京施安泰医药技术开发有限公司 | 四氢吡咯并[2,1-h]蝶啶-6(5H)-酮衍生物、其药物组合物、制备方法和应用 |
| WO2020076728A1 (en) | 2018-10-08 | 2020-04-16 | Takeda Pharmaceutical Company Limited | SUBSTITUTED OXAZINOPTERIDINONES AS INHIBITORS OF mTOR |
| WO2023083297A1 (en) * | 2021-11-12 | 2023-05-19 | Insilico Medicine Ip Limited | Small molecule inhibitors of ubiquitin specific protease 1 (usp1) and uses thereof |
| CN114369064B (zh) * | 2022-01-10 | 2023-12-19 | 北京莱瑞森医药科技有限公司 | 一种西地那非中间体的制备方法 |
| CN114671810B (zh) * | 2022-03-21 | 2024-03-22 | 济南鸿湾生物技术有限公司 | 一种咪唑苯脲的制备方法 |
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| WO2009103010A2 (en) | 2008-02-13 | 2009-08-20 | Elan Pharmaceuticals, Inc. | Alpha-synuclein kinase |
| EP2112152A1 (en) | 2008-04-22 | 2009-10-28 | GPC Biotech AG | Dihydropteridinones as Plk Inhibitors |
| GB0807451D0 (en) | 2008-04-24 | 2008-05-28 | Chroma Therapeutics Ltd | Inhibitors of PLK |
| CA2745295C (en) | 2008-12-09 | 2017-01-10 | Gilead Sciences, Inc. | Modulators of toll-like receptors |
| CN101544642A (zh) * | 2009-03-12 | 2009-09-30 | 山东省医药工业研究所 | 4-蝶啶氨类化合物及其制备和用途 |
| ES2432315T3 (es) | 2009-08-28 | 2013-12-02 | Takeda Pharmaceutical Company Limited | Compuestos de hexahidrooxazinopterina para su uso como inhibidores de mTOR |
| CN102020643A (zh) | 2009-09-22 | 2011-04-20 | 上海恒瑞医药有限公司 | 二氢喋啶酮类衍生物、其制备方法及其在医药上的应用 |
| EP2536725B1 (en) | 2010-02-17 | 2015-10-28 | Boehringer Ingelheim International GmbH | Dihydropteridinones, method for production and use thereof |
-
2010
- 2010-12-21 CA CA 2783258 patent/CA2783258A1/en not_active Abandoned
- 2010-12-21 US US12/974,401 patent/US8445503B2/en not_active Expired - Fee Related
- 2010-12-21 SG SG2012046769A patent/SG181908A1/en unknown
- 2010-12-21 WO PCT/US2010/061535 patent/WO2011079114A1/en not_active Ceased
- 2010-12-21 BR BR112012015714A patent/BR112012015714A2/pt not_active IP Right Cessation
- 2010-12-21 JP JP2012546150A patent/JP2013515734A/ja active Pending
- 2010-12-21 EP EP20100798439 patent/EP2516441B1/en active Active
- 2010-12-21 WO PCT/US2010/061551 patent/WO2011079118A1/en not_active Ceased
- 2010-12-21 MX MX2012007273A patent/MX2012007273A/es active IP Right Grant
- 2010-12-21 RU RU2012131124/04A patent/RU2012131124A/ru not_active Application Discontinuation
- 2010-12-21 PH PH1/2012/501122A patent/PH12012501122A1/en unknown
- 2010-12-21 CN CN2010800645410A patent/CN102762568A/zh active Pending
- 2010-12-21 AU AU2010336509A patent/AU2010336509A1/en not_active Abandoned
- 2010-12-21 KR KR20127019405A patent/KR20120120252A/ko not_active Withdrawn
- 2010-12-21 US US12/974,622 patent/US8541418B2/en not_active Expired - Fee Related
-
2012
- 2012-06-06 ZA ZA2012/04136A patent/ZA201204136B/en unknown
- 2012-06-21 IL IL220563A patent/IL220563A0/en unknown
-
2013
- 2013-04-17 US US13/864,332 patent/US20130231335A1/en not_active Abandoned
- 2013-08-14 US US13/966,434 patent/US20130331376A1/en not_active Abandoned
-
2015
- 2015-01-14 US US14/596,824 patent/US20150126502A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| RU2012131124A (ru) | 2014-01-27 |
| CN102762568A (zh) | 2012-10-31 |
| KR20120120252A (ko) | 2012-11-01 |
| US20110207716A1 (en) | 2011-08-25 |
| US20130331376A1 (en) | 2013-12-12 |
| JP2013515734A (ja) | 2013-05-09 |
| IL220563A0 (en) | 2012-08-30 |
| ZA201204136B (en) | 2013-08-28 |
| US20150126502A1 (en) | 2015-05-07 |
| US8445503B2 (en) | 2013-05-21 |
| EP2516441B1 (en) | 2015-01-21 |
| US20130231335A1 (en) | 2013-09-05 |
| PH12012501122A1 (en) | 2012-10-29 |
| US20110212942A1 (en) | 2011-09-01 |
| US8541418B2 (en) | 2013-09-24 |
| SG181908A1 (en) | 2012-08-30 |
| BR112012015714A2 (pt) | 2017-04-25 |
| CA2783258A1 (en) | 2011-06-30 |
| AU2010336509A1 (en) | 2012-07-19 |
| WO2011079118A1 (en) | 2011-06-30 |
| WO2011079114A1 (en) | 2011-06-30 |
| EP2516441A1 (en) | 2012-10-31 |
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