PE20150902A1 - Compuestos de 2-fenil-5-heterociclil-tetrahidro-2h-piran-3-amina para uso en el tratamiento de diabetes y sus trastornos asociado - Google Patents
Compuestos de 2-fenil-5-heterociclil-tetrahidro-2h-piran-3-amina para uso en el tratamiento de diabetes y sus trastornos asociadoInfo
- Publication number
- PE20150902A1 PE20150902A1 PE2015000501A PE2015000501A PE20150902A1 PE 20150902 A1 PE20150902 A1 PE 20150902A1 PE 2015000501 A PE2015000501 A PE 2015000501A PE 2015000501 A PE2015000501 A PE 2015000501A PE 20150902 A1 PE20150902 A1 PE 20150902A1
- Authority
- PE
- Peru
- Prior art keywords
- treatment
- diabetes
- heterociclil
- tetrahidro
- piran
- Prior art date
Links
- 206010012601 diabetes mellitus Diseases 0.000 title abstract 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title 1
- -1 2,5-difluorophenyl Chemical group 0.000 abstract 4
- 150000001875 compounds Chemical class 0.000 abstract 3
- 208000008589 Obesity Diseases 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 208000030159 metabolic disease Diseases 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 235000020824 obesity Nutrition 0.000 abstract 1
- WUUOEJJGRCQGBQ-UHFFFAOYSA-N oxan-3-amine Chemical compound NC1CCCOC1 WUUOEJJGRCQGBQ-UHFFFAOYSA-N 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 229940002612 prodrug Drugs 0.000 abstract 1
- 239000000651 prodrug Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
Classifications
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- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- 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
-
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed 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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed 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
- C07D487/02—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 two hetero rings
- C07D487/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—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
- 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
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—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
- 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
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
-
- 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
- C07D495/02—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 two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (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)
- Epidemiology (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
La invencion se relaciona con compuestos de la formula general (I) sus formas tautomericas, sus enatiomeros, sus diastereomeros, sus sales farmaceuticamente aceptadas, o pro-farmacos de los mismos, que son utiles para el tratamiento o prevencion de diabetes mellitus (DM), obesidad y otros trastornos metabolicos. La invencion tambien se relaciona con el proceso para la fabricacion de dichos compuestos, y composiciones farmaceuticas que los contienen y su uso. Los compuestos preferidos son: (2R, 3S, 5R)-2-(2,5-difluorofenil)-5-(5-(metilsulfonil)-hexahidro-pirrolo [3,4-c]pirrol-2 (1H)-il) tetrahidro-2H-piran-3 amina; (2R S,5R)-2-(2,5-difluorofenil)-5-(7-(metilsulfonil)-2,7-diazaspiro [4. 4]-nonan-2-il) tetrahidro-2H-piran-3-anima, entre otros
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN3030MU2012 | 2012-10-17 |
Publications (1)
Publication Number | Publication Date |
---|---|
PE20150902A1 true PE20150902A1 (es) | 2015-06-25 |
Family
ID=49917687
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PE2015000501A PE20150902A1 (es) | 2012-10-17 | 2013-10-17 | Compuestos de 2-fenil-5-heterociclil-tetrahidro-2h-piran-3-amina para uso en el tratamiento de diabetes y sus trastornos asociado |
Country Status (23)
Country | Link |
---|---|
US (1) | US20150246025A1 (es) |
EP (1) | EP2909199A1 (es) |
JP (1) | JP2016500685A (es) |
KR (1) | KR20150070325A (es) |
CN (1) | CN104736534A (es) |
AP (1) | AP2015008366A0 (es) |
AR (1) | AR093047A1 (es) |
AU (1) | AU2013333405A1 (es) |
BR (1) | BR112015008717A2 (es) |
CA (1) | CA2886710A1 (es) |
CL (1) | CL2015000976A1 (es) |
CO (1) | CO7350641A2 (es) |
EA (1) | EA201590735A1 (es) |
HK (1) | HK1207860A1 (es) |
IL (1) | IL238027A0 (es) |
MA (1) | MA38079A1 (es) |
MX (1) | MX2015004846A (es) |
PE (1) | PE20150902A1 (es) |
PH (1) | PH12015500860A1 (es) |
SG (1) | SG11201502653VA (es) |
TW (1) | TWI500613B (es) |
WO (1) | WO2014061031A1 (es) |
ZA (1) | ZA201502290B (es) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105085528A (zh) * | 2014-05-15 | 2015-11-25 | 成都贝斯凯瑞生物科技有限公司 | 作为二肽基肽酶-iv抑制剂的氨基四氢吡喃衍生物 |
WO2016014324A1 (en) * | 2014-07-21 | 2016-01-28 | Merck Sharp & Dohme Corp. | Process for preparing chiral dipeptidyl peptidase-iv inhibitors |
CN106478631B (zh) * | 2015-08-24 | 2019-04-05 | 四川科伦药物研究院有限公司 | 长效二肽基肽酶-iv抑制剂、用途及其中间体的制备方法 |
TWI682933B (zh) * | 2015-08-27 | 2020-01-21 | 大陸商四川海思科製藥有限公司 | 三員稠合環取代的胺基六員環類衍生物及其在醫藥上的應用 |
CN105198847B (zh) * | 2015-10-28 | 2017-05-17 | 四川凯科医药科技有限公司 | 一种化合物的制备方法 |
CN106146405B (zh) * | 2016-06-22 | 2018-11-30 | 湖北生物医药产业技术研究院有限公司 | 药物杂质中间体及其制备方法和用途 |
RS59306B1 (sr) * | 2017-03-20 | 2019-10-31 | Forma Therapeutics Inc | Kompozicije pirolopirola kao aktivatori piruvat kinaze (pkr) |
BR112021005188A2 (pt) | 2018-09-19 | 2021-06-08 | Forma Therapeutics, Inc. | tratamento de anemia falciforme com um composto de ativação de piruvato cinase r |
US12122778B2 (en) | 2018-09-19 | 2024-10-22 | Novo Nordisk Health Care Ag | Activating pyruvate kinase R |
CN109928971B (zh) * | 2019-03-14 | 2024-01-16 | 广东东阳光药业股份有限公司 | 芳基取代的氨基四氢吡喃类化合物及其用途 |
US12128035B2 (en) | 2021-03-19 | 2024-10-29 | Novo Nordisk Health Care Ag | Activating pyruvate kinase R |
CN115304605B (zh) * | 2022-01-21 | 2023-10-03 | 陕西国际商贸学院 | 具有抗肿瘤活性的氧杂环丁烷衍生物及其制备方法和应用 |
WO2024112764A1 (en) | 2022-11-21 | 2024-05-30 | Novo Nordisk Health Care Ag | Synthesis of pyrrolo[3,4-c]pyrroles |
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IL111785A0 (en) | 1993-12-03 | 1995-01-24 | Ferring Bv | Dp-iv inhibitors and pharmaceutical compositions containing them |
DE122010000020I1 (de) | 1996-04-25 | 2010-07-08 | Prosidion Ltd | Verfahren zur Senkung des Blutglukosespiegels in Säugern |
TW492957B (en) | 1996-11-07 | 2002-07-01 | Novartis Ag | N-substituted 2-cyanopyrrolidnes |
US6011155A (en) | 1996-11-07 | 2000-01-04 | Novartis Ag | N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
CO5150173A1 (es) | 1998-12-10 | 2002-04-29 | Novartis Ag | Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv |
US6107317A (en) | 1999-06-24 | 2000-08-22 | Novartis Ag | N-(substituted glycyl)-thiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
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-
2013
- 2013-10-16 TW TW102137331A patent/TWI500613B/zh not_active IP Right Cessation
- 2013-10-17 CN CN201380054443.2A patent/CN104736534A/zh active Pending
- 2013-10-17 SG SG11201502653VA patent/SG11201502653VA/en unknown
- 2013-10-17 BR BR112015008717A patent/BR112015008717A2/pt not_active IP Right Cessation
- 2013-10-17 KR KR1020157012688A patent/KR20150070325A/ko not_active Application Discontinuation
- 2013-10-17 PE PE2015000501A patent/PE20150902A1/es not_active Application Discontinuation
- 2013-10-17 JP JP2015537421A patent/JP2016500685A/ja not_active Ceased
- 2013-10-17 US US14/436,504 patent/US20150246025A1/en not_active Abandoned
- 2013-10-17 AP AP2015008366A patent/AP2015008366A0/xx unknown
- 2013-10-17 WO PCT/IN2013/000627 patent/WO2014061031A1/en active Application Filing
- 2013-10-17 AU AU2013333405A patent/AU2013333405A1/en not_active Abandoned
- 2013-10-17 EP EP13817742.3A patent/EP2909199A1/en not_active Withdrawn
- 2013-10-17 MA MA38079A patent/MA38079A1/fr unknown
- 2013-10-17 MX MX2015004846A patent/MX2015004846A/es unknown
- 2013-10-17 CA CA2886710A patent/CA2886710A1/en not_active Abandoned
- 2013-10-17 AR ARP130103771A patent/AR093047A1/es unknown
- 2013-10-17 EA EA201590735A patent/EA201590735A1/ru unknown
-
2015
- 2015-03-30 IL IL238027A patent/IL238027A0/en unknown
- 2015-04-07 ZA ZA2015/02290A patent/ZA201502290B/en unknown
- 2015-04-16 CO CO15085319A patent/CO7350641A2/es unknown
- 2015-04-16 CL CL2015000976A patent/CL2015000976A1/es unknown
- 2015-04-17 PH PH12015500860A patent/PH12015500860A1/en unknown
- 2015-08-31 HK HK15108497.4A patent/HK1207860A1/xx unknown
Also Published As
Publication number | Publication date |
---|---|
BR112015008717A2 (pt) | 2017-07-04 |
SG11201502653VA (en) | 2015-05-28 |
WO2014061031A1 (en) | 2014-04-24 |
US20150246025A1 (en) | 2015-09-03 |
AP2015008366A0 (en) | 2015-04-30 |
EA201590735A1 (ru) | 2016-04-29 |
CN104736534A (zh) | 2015-06-24 |
CO7350641A2 (es) | 2015-08-10 |
TW201429960A (zh) | 2014-08-01 |
EP2909199A1 (en) | 2015-08-26 |
AU2013333405A1 (en) | 2015-05-07 |
MX2015004846A (es) | 2015-07-21 |
KR20150070325A (ko) | 2015-06-24 |
JP2016500685A (ja) | 2016-01-14 |
MA38079A1 (fr) | 2016-09-30 |
CA2886710A1 (en) | 2014-04-24 |
CL2015000976A1 (es) | 2015-12-18 |
AR093047A1 (es) | 2015-05-13 |
PH12015500860A1 (en) | 2015-06-22 |
HK1207860A1 (en) | 2016-02-12 |
ZA201502290B (en) | 2016-01-27 |
TWI500613B (zh) | 2015-09-21 |
IL238027A0 (en) | 2015-05-31 |
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