PE20160860A1 - Derivados de etinil-imidazolidin-2,4-diona como moduladores de mglur 4 - Google Patents
Derivados de etinil-imidazolidin-2,4-diona como moduladores de mglur 4Info
- Publication number
- PE20160860A1 PE20160860A1 PE2016000958A PE2016000958A PE20160860A1 PE 20160860 A1 PE20160860 A1 PE 20160860A1 PE 2016000958 A PE2016000958 A PE 2016000958A PE 2016000958 A PE2016000958 A PE 2016000958A PE 20160860 A1 PE20160860 A1 PE 20160860A1
- Authority
- PE
- Peru
- Prior art keywords
- phenyl
- imidazolidine
- dione
- modulators
- alkyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 abstract 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 3
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 abstract 2
- PODGWZAGEWXSLD-UHFFFAOYSA-N 1-ethynylimidazolidine-2,4-dione Chemical compound C(#C)N1C(NC(C1)=O)=O PODGWZAGEWXSLD-UHFFFAOYSA-N 0.000 abstract 1
- -1 2-phenylethynyl Chemical group 0.000 abstract 1
- XUWBZYFUJHXHKH-UHFFFAOYSA-N 3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1-propan-2-ylimidazolidine-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N(CC1=O)C(C)C)=O XUWBZYFUJHXHKH-UHFFFAOYSA-N 0.000 abstract 1
- 206010003805 Autism Diseases 0.000 abstract 1
- 208000020706 Autistic disease Diseases 0.000 abstract 1
- 102100038354 Metabotropic glutamate receptor 4 Human genes 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 abstract 1
- 208000018737 Parkinson disease Diseases 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 230000003281 allosteric effect Effects 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 1
- 108010038422 metabotropic glutamate receptor 4 Proteins 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 125000004076 pyridyl group Chemical group 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/74—Two oxygen atoms, e.g. hydantoin with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to other ring members
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- 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
- A61P25/22—Anxiolytics
-
- 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
- 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
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B55/00—Racemisation; Complete or partial inversion
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen 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
- 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
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- 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
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- 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
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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- 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
- C07D498/02—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 two hetero rings
- C07D498/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Otolaryngology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
La presente invencion se refiere a compuestos derivados de etinil-imidazolidin-2,4-diona de formula I donde Y es C-R1, R1 es H o halogeno; R2 es H, alquilo C1-C7 o fenilo; R4 es H o alquilo inferior o R2 y R4 pueden formar conjuntamente los anillos (A), (B), entre otros; R5 es H o alquilo C1-C7 o R4 y R5 pueden formar un anillo heterocicloalquilo; R3 es fenilo o piridinilo. Son compuestos preferidos: 3-[2,6-difluoro-4-(2-feniletinil)fenil]-1-isopropil-imidazolidin-2,4-diona; (5RS)-3-[2,6-difrluoro-4-(2-feniletinil)fenil]-1-isopropil-5-metil-imidazolidin-2,4-diona. Tambien se refiere a un metodo de preparacion. Dichos compuestos son moduladores alostericos del receptor de mGluR4, siendo utiles en el tratamiento de la enfermedad de Parkinson, el trastorno obsesivo-compulsivo, el autismo, el cancer, la diabetes de tipo 2, entre otros
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14150700 | 2014-01-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20160860A1 true PE20160860A1 (es) | 2016-09-03 |
Family
ID=49917002
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2016000958A PE20160860A1 (es) | 2014-01-10 | 2015-01-07 | Derivados de etinil-imidazolidin-2,4-diona como moduladores de mglur 4 |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US9695128B2 (es) |
| EP (1) | EP3092219B1 (es) |
| JP (1) | JP6263633B2 (es) |
| KR (1) | KR101868248B1 (es) |
| CN (1) | CN106170479B (es) |
| AR (1) | AR099047A1 (es) |
| AU (1) | AU2015205661B2 (es) |
| BR (1) | BR112016010168A2 (es) |
| CA (1) | CA2934768A1 (es) |
| CL (1) | CL2016001739A1 (es) |
| CR (1) | CR20160198A (es) |
| EA (1) | EA029967B1 (es) |
| IL (1) | IL245327B (es) |
| MX (1) | MX369820B (es) |
| PE (1) | PE20160860A1 (es) |
| PH (1) | PH12016501100A1 (es) |
| SG (1) | SG11201605557TA (es) |
| TW (1) | TWI649310B (es) |
| UA (1) | UA119053C2 (es) |
| WO (1) | WO2015104271A1 (es) |
| ZA (1) | ZA201602890B (es) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6286577B2 (ja) * | 2014-02-25 | 2018-02-28 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | エチニル誘導体 |
| MX374409B (es) | 2015-07-15 | 2025-03-04 | Hoffmann La Roche | Derivados de etinilo como moduladores del receptor de glutamato metabotrópico. |
| AR105556A1 (es) * | 2015-08-03 | 2017-10-18 | Hoffmann La Roche | Derivados de etinilo |
| PL3484889T3 (pl) | 2016-07-18 | 2020-12-28 | F. Hoffmann-La Roche Ag | Pochodne etynylu |
| EP3668873B1 (en) | 2017-08-17 | 2021-06-30 | F. Hoffmann-La Roche AG | Imidazo[1,2-a]imidazol-2-one derivatives for the treatment of diseases such as parkinson's disease |
| US10517713B2 (en) | 2018-01-10 | 2019-12-31 | Cook Medical Technologies Llc | Vascular graft with helical flow compliance compartments |
| US10893929B2 (en) | 2018-01-10 | 2021-01-19 | Cook Medical Technologies Llc | Vascular graft with compartments for compliance matching |
| EP3827001A1 (en) | 2018-07-26 | 2021-06-02 | Domain Therapeutics | Substituted quinazolinone derivatives and their use as positive allosteric modulators of mglur4 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2009013169A (es) * | 2007-06-03 | 2010-04-30 | Univ Vanderbilt | Moduladores alostericos positivos del mglur5 benzamida y metodos de elaboracion y uso de los mismos. |
| CA2773038A1 (en) * | 2009-09-04 | 2011-03-10 | P. Jeffrey Conn | Mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction |
| US8420661B2 (en) * | 2010-04-13 | 2013-04-16 | Hoffmann-La Roche Inc. | Arylethynyl derivatives |
| WO2012162635A1 (en) * | 2011-05-26 | 2012-11-29 | Sunovion Pharmaceuticals Inc. | Metabotropic glutamate receptors 5 modulators and methods of use thereof |
-
2015
- 2015-01-06 TW TW104100333A patent/TWI649310B/zh not_active IP Right Cessation
- 2015-01-07 CN CN201580002922.9A patent/CN106170479B/zh not_active Expired - Fee Related
- 2015-01-07 MX MX2016008887A patent/MX369820B/es active IP Right Grant
- 2015-01-07 BR BR112016010168A patent/BR112016010168A2/pt not_active IP Right Cessation
- 2015-01-07 SG SG11201605557TA patent/SG11201605557TA/en unknown
- 2015-01-07 EA EA201691046A patent/EA029967B1/ru not_active IP Right Cessation
- 2015-01-07 AU AU2015205661A patent/AU2015205661B2/en not_active Ceased
- 2015-01-07 EP EP15700850.9A patent/EP3092219B1/en active Active
- 2015-01-07 CA CA2934768A patent/CA2934768A1/en not_active Abandoned
- 2015-01-07 KR KR1020167018069A patent/KR101868248B1/ko not_active Expired - Fee Related
- 2015-01-07 PE PE2016000958A patent/PE20160860A1/es unknown
- 2015-01-07 JP JP2016545871A patent/JP6263633B2/ja not_active Expired - Fee Related
- 2015-01-07 WO PCT/EP2015/050127 patent/WO2015104271A1/en not_active Ceased
- 2015-01-08 AR ARP150100038A patent/AR099047A1/es unknown
- 2015-07-01 UA UAA201608260A patent/UA119053C2/uk unknown
-
2016
- 2016-04-27 IL IL245327A patent/IL245327B/en active IP Right Grant
- 2016-04-28 ZA ZA2016/02890A patent/ZA201602890B/en unknown
- 2016-04-28 CR CR20160198A patent/CR20160198A/es unknown
- 2016-06-09 PH PH12016501100A patent/PH12016501100A1/en unknown
- 2016-07-07 CL CL2016001739A patent/CL2016001739A1/es unknown
- 2016-07-08 US US15/205,466 patent/US9695128B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN106170479B (zh) | 2019-02-12 |
| CA2934768A1 (en) | 2015-07-16 |
| PH12016501100B1 (en) | 2016-07-11 |
| BR112016010168A2 (pt) | 2017-08-08 |
| JP6263633B2 (ja) | 2018-01-17 |
| SG11201605557TA (en) | 2016-08-30 |
| CR20160198A (es) | 2016-06-17 |
| CL2016001739A1 (es) | 2017-05-12 |
| EA201691046A1 (ru) | 2016-12-30 |
| KR20160095099A (ko) | 2016-08-10 |
| US20170008854A1 (en) | 2017-01-12 |
| IL245327B (en) | 2018-12-31 |
| IL245327A0 (en) | 2016-06-30 |
| CN106170479A (zh) | 2016-11-30 |
| PH12016501100A1 (en) | 2016-07-11 |
| AU2015205661B2 (en) | 2018-08-23 |
| ZA201602890B (en) | 2017-07-26 |
| UA119053C2 (uk) | 2019-04-25 |
| EP3092219B1 (en) | 2018-09-19 |
| KR101868248B1 (ko) | 2018-06-15 |
| US9695128B2 (en) | 2017-07-04 |
| AR099047A1 (es) | 2016-06-22 |
| TWI649310B (zh) | 2019-02-01 |
| HK1226054A1 (zh) | 2017-09-22 |
| WO2015104271A1 (en) | 2015-07-16 |
| MX2016008887A (es) | 2016-10-04 |
| JP2017502066A (ja) | 2017-01-19 |
| EP3092219A1 (en) | 2016-11-16 |
| MX369820B (es) | 2019-11-22 |
| TW201531464A (zh) | 2015-08-16 |
| EA029967B1 (ru) | 2018-06-29 |
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