MX2018007450A - Compuestos de diamina-arilsulfonamida sustituidos con hidroxialquilamina e hidroxicicloalquilamina con actividad selectiva en canales de sodio activados por voltaje. - Google Patents
Compuestos de diamina-arilsulfonamida sustituidos con hidroxialquilamina e hidroxicicloalquilamina con actividad selectiva en canales de sodio activados por voltaje.Info
- Publication number
- MX2018007450A MX2018007450A MX2018007450A MX2018007450A MX2018007450A MX 2018007450 A MX2018007450 A MX 2018007450A MX 2018007450 A MX2018007450 A MX 2018007450A MX 2018007450 A MX2018007450 A MX 2018007450A MX 2018007450 A MX2018007450 A MX 2018007450A
- Authority
- MX
- Mexico
- Prior art keywords
- hydroxycycloalkylamine
- hydroxyalkylamine
- voltage
- sodium channels
- compounds
- Prior art date
Links
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 title 1
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 3
- 150000003839 salts Chemical class 0.000 abstract 2
- 206010011224 Cough Diseases 0.000 abstract 1
- 102000004310 Ion Channels Human genes 0.000 abstract 1
- 208000003251 Pruritus Diseases 0.000 abstract 1
- 208000027520 Somatoform disease Diseases 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 210000002569 neuron Anatomy 0.000 abstract 1
- 208000027753 pain disease Diseases 0.000 abstract 1
- 230000002093 peripheral effect Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 230000002889 sympathetic effect Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/08—1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
-
- 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
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further 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
- A61K31/41—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
- A61K31/433—Thidiazoles
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
- C07D277/38—Nitrogen atoms
- C07D277/50—Nitrogen atoms bound to hetero atoms
- C07D277/52—Nitrogen atoms bound to hetero atoms to sulfur atoms, e.g. sulfonamides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Cephalosporin Compounds (AREA)
Abstract
Se divulgan compuestos de Fórmula A, o una sal del mismo: (ver Fórmula A) en donde R1, R2 y E se definen en el presente documento, dichos compuestos que tienen propiedades para inhibir los canales de iones Nav1.7 encontrados en neuronas perifericas y simpaticas; tambien se describen formulaciones farmaceuticas que comprenden los compuestos de Formula A o sus sales, y metodos de tratamiento de trastornos de dolor, tos, y picazon usando las mismas.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562269327P | 2015-12-18 | 2015-12-18 | |
| US201662290235P | 2016-02-02 | 2016-02-02 | |
| US201662420956P | 2016-11-11 | 2016-11-11 | |
| PCT/US2016/066445 WO2017106226A1 (en) | 2015-12-18 | 2016-12-14 | Hydroxyalkylamine- and hydroxycycloalkylamine-substituted diamine-arylsulfonamide compounds with selective activity in voltage-gated sodium channels |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2018007450A true MX2018007450A (es) | 2018-11-14 |
Family
ID=57708830
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2018007450A MX2018007450A (es) | 2015-12-18 | 2016-12-14 | Compuestos de diamina-arilsulfonamida sustituidos con hidroxialquilamina e hidroxicicloalquilamina con actividad selectiva en canales de sodio activados por voltaje. |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US10221167B2 (es) |
| EP (1) | EP3390374B1 (es) |
| JP (1) | JP6572392B2 (es) |
| KR (1) | KR20180095598A (es) |
| CN (1) | CN108699015A (es) |
| AR (1) | AR106987A1 (es) |
| AU (1) | AU2016370554B2 (es) |
| BR (1) | BR112018012327A2 (es) |
| CA (1) | CA3008611A1 (es) |
| CL (1) | CL2018001640A1 (es) |
| CO (1) | CO2018006137A2 (es) |
| CR (1) | CR20180322A (es) |
| DO (1) | DOP2018000150A (es) |
| EA (1) | EA201891313A1 (es) |
| EC (1) | ECSP18052850A (es) |
| HK (1) | HK1255027A1 (es) |
| IL (1) | IL260052A (es) |
| MX (1) | MX2018007450A (es) |
| NI (1) | NI201800067A (es) |
| PE (1) | PE20181495A1 (es) |
| PH (1) | PH12018501288A1 (es) |
| SG (1) | SG11201804936UA (es) |
| SV (1) | SV2018005708A (es) |
| TN (1) | TN2018000195A1 (es) |
| TW (1) | TW201726637A (es) |
| WO (1) | WO2017106226A1 (es) |
| ZA (1) | ZA201803591B (es) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12084472B2 (en) | 2015-12-18 | 2024-09-10 | Ardelyx, Inc. | Substituted 4-phenyl pyridine compounds as non-systemic TGR5 agonists |
| JP6572392B2 (ja) * | 2015-12-18 | 2019-09-11 | メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. | 電位作動型ナトリウムチャネルにおいて選択的活性を有する、ヒドロキシアルキルアミンおよびヒドロキシシクロアルキルアミンで置換されたジアミン−アリールスルホンアミド化合物 |
| AU2016370677A1 (en) * | 2015-12-18 | 2018-06-07 | Merck Sharp & Dohme Corp. | Diamino-alkylamino-linked arylsulfonamide compounds with selective activity in voltage-gated sodium channels |
| TWI773657B (zh) | 2015-12-18 | 2022-08-11 | 美商亞德利克斯公司 | 作爲非全身tgr5促效劑之經取代之4-苯基吡啶化合物 |
| CN110072855A (zh) | 2016-10-17 | 2019-07-30 | 基因泰克公司 | 治疗性化合物及其使用方法 |
| EP3532462B1 (en) * | 2016-10-27 | 2021-10-13 | Bristol-Myers Squibb Company | Acyl sulfonamide nav1.7 inhibitors |
| EP3541373B1 (en) | 2016-11-17 | 2023-11-01 | Merck Sharp & Dohme LLC | Diamino-alkylamino-linked arylsulfonamide compounds with selective activity in voltage-gated sodium channels |
| EP3601273B1 (en) | 2017-03-24 | 2021-12-01 | Genentech, Inc. | 4-piperidin-n-(pyrimidin-4-yl)chroman-7-sulfonamide derivatives as sodium channel inhibitors |
| US11028075B2 (en) | 2018-02-26 | 2021-06-08 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| CN111936494A (zh) | 2018-03-30 | 2020-11-13 | 豪夫迈·罗氏有限公司 | 作为钠通道抑制剂的取代的氢-吡啶并-吖嗪 |
| TW202003490A (zh) | 2018-05-22 | 2020-01-16 | 瑞士商赫孚孟拉羅股份公司 | 治療性化合物及其使用方法 |
| IL279810B2 (en) | 2018-08-31 | 2025-03-01 | Xenon Pharmaceuticals Inc | Heteroaryl-modified sulfonamide compounds and their use as medicinal agents |
| CN111285825B (zh) * | 2018-12-10 | 2023-02-17 | 中国科学院上海药物研究所 | 一类苯磺酰胺取代的衍生物,其制法及其用途 |
| WO2020248123A1 (en) | 2019-06-11 | 2020-12-17 | Merck Sharp & Dohme Corp. | Hydroxypyrrolidine-substituted arylsulfonamide compounds with selective activity in voltage-gated sodium channels |
| CN113527281B (zh) * | 2020-04-20 | 2023-12-22 | 昆山彭济凯丰生物科技有限公司 | 杂环化合物及其制备方法和应用 |
| CN117362206B (zh) * | 2023-12-08 | 2024-02-20 | 四川大学华西第二医院 | 一类芳基磺酰胺类化合物、合成方法及用途 |
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| WO2005013914A2 (en) * | 2003-08-08 | 2005-02-17 | Vertex Pharmaceuticals Incorporated | Heteroarylaminosulfonylphenyl derivatives for use as sodium or calcium channel blockers in the treatment of pain |
| MY158766A (en) | 2005-04-11 | 2016-11-15 | Xenon Pharmaceuticals Inc | Spiro-oxindole compounds and their uses as therapeutic agents |
| RU2009117642A (ru) | 2006-10-12 | 2010-11-20 | Ксенон Фармасьютикалз Инк. (Ca) | Применение спирооксиндоловых соединений в качестве терапевтических средств |
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| BR112014010197A2 (pt) | 2011-10-28 | 2017-04-18 | Merck Sharp & Dohme | composto, composição farmacêutica, método de tratamento de um distúrbio |
| CN104024251B (zh) | 2011-10-31 | 2017-08-11 | 克赛农制药股份有限公司 | 苯磺酰胺化合物及其作为治疗剂的用途 |
| CN104093716B (zh) | 2011-10-31 | 2017-06-23 | 克赛农制药股份有限公司 | 联芳醚磺酰胺化合物及其作为治疗剂的用途 |
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| US20150291514A1 (en) | 2012-01-04 | 2015-10-15 | Pfizer Limted | N-Aminosulfonyl Benzamides |
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| AR091112A1 (es) | 2012-05-22 | 2015-01-14 | Genentech Inc | Benzamidas n-sustituidas como inhibidores de los canales de sodio nav1.7 |
| BR112015000187A2 (pt) | 2012-07-06 | 2017-06-27 | Genentech Inc | benzamidas substituídas com n e métodos de uso das mesmas |
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| JP2015535251A (ja) | 2012-10-26 | 2015-12-10 | メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. | 電位作動型ナトリウムチャネルにおいて選択的活性を有するベンゾオキサゾリノン化合物 |
| AU2013334664A1 (en) | 2012-10-26 | 2015-05-07 | Merck Sharp & Dohme Corp. | N-substituted indazole sulfonamide compounds with selective activity in voltage-gated sodium channels |
| JP2014101287A (ja) | 2012-11-16 | 2014-06-05 | Daiichi Sankyo Co Ltd | インドール誘導体 |
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| EP2968234B1 (en) | 2013-03-15 | 2018-06-27 | Chromocell Corporation | Sodium channel modulators for the treatment of pain |
| MX2015010775A (es) | 2013-03-15 | 2016-04-25 | Genentech Inc | Benzoxazoles sustituidos y metodos para usarlos. |
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| CA2917198C (en) | 2013-07-10 | 2022-06-07 | Vertex Pharmaceuticals Incorporated | Fused piperidine amides as modulators of ion channels |
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| AU2016370677A1 (en) | 2015-12-18 | 2018-06-07 | Merck Sharp & Dohme Corp. | Diamino-alkylamino-linked arylsulfonamide compounds with selective activity in voltage-gated sodium channels |
| JP6572392B2 (ja) * | 2015-12-18 | 2019-09-11 | メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. | 電位作動型ナトリウムチャネルにおいて選択的活性を有する、ヒドロキシアルキルアミンおよびヒドロキシシクロアルキルアミンで置換されたジアミン−アリールスルホンアミド化合物 |
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| EP3541373B1 (en) | 2016-11-17 | 2023-11-01 | Merck Sharp & Dohme LLC | Diamino-alkylamino-linked arylsulfonamide compounds with selective activity in voltage-gated sodium channels |
-
2016
- 2016-12-14 JP JP2018531094A patent/JP6572392B2/ja not_active Expired - Fee Related
- 2016-12-14 TN TNP/2018/000195A patent/TN2018000195A1/en unknown
- 2016-12-14 US US15/378,465 patent/US10221167B2/en active Active
- 2016-12-14 KR KR1020187020090A patent/KR20180095598A/ko not_active Abandoned
- 2016-12-14 BR BR112018012327A patent/BR112018012327A2/pt not_active Application Discontinuation
- 2016-12-14 EA EA201891313A patent/EA201891313A1/ru unknown
- 2016-12-14 WO PCT/US2016/066445 patent/WO2017106226A1/en not_active Ceased
- 2016-12-14 AU AU2016370554A patent/AU2016370554B2/en not_active Ceased
- 2016-12-14 CN CN201680081234.0A patent/CN108699015A/zh active Pending
- 2016-12-14 MX MX2018007450A patent/MX2018007450A/es unknown
- 2016-12-14 EP EP16820497.2A patent/EP3390374B1/en active Active
- 2016-12-14 HK HK18114148.2A patent/HK1255027A1/zh unknown
- 2016-12-14 CR CR20180322A patent/CR20180322A/es unknown
- 2016-12-14 TW TW105141337A patent/TW201726637A/zh unknown
- 2016-12-14 PE PE2018001100A patent/PE20181495A1/es unknown
- 2016-12-14 SG SG11201804936UA patent/SG11201804936UA/en unknown
- 2016-12-14 AR ARP160103829A patent/AR106987A1/es unknown
- 2016-12-14 CA CA3008611A patent/CA3008611A1/en not_active Abandoned
-
2018
- 2018-05-30 ZA ZA2018/03591A patent/ZA201803591B/en unknown
- 2018-06-12 NI NI201800067A patent/NI201800067A/es unknown
- 2018-06-13 SV SV2018005708A patent/SV2018005708A/es unknown
- 2018-06-14 IL IL260052A patent/IL260052A/en unknown
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- 2018-06-15 CO CONC2018/0006137A patent/CO2018006137A2/es unknown
- 2018-06-15 CL CL2018001640A patent/CL2018001640A1/es unknown
- 2018-06-18 DO DO2018000150A patent/DOP2018000150A/es unknown
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2019
- 2019-01-11 US US16/246,068 patent/US20190233406A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP3390374A1 (en) | 2018-10-24 |
| US20170174674A1 (en) | 2017-06-22 |
| HK1255027A1 (zh) | 2019-08-02 |
| PH12018501288A1 (en) | 2019-01-28 |
| TW201726637A (zh) | 2017-08-01 |
| AU2016370554B2 (en) | 2018-11-29 |
| ZA201803591B (en) | 2019-04-24 |
| CL2018001640A1 (es) | 2018-08-03 |
| US10221167B2 (en) | 2019-03-05 |
| EP3390374B1 (en) | 2020-08-26 |
| CR20180322A (es) | 2018-08-21 |
| IL260052A (en) | 2018-07-31 |
| CA3008611A1 (en) | 2017-06-22 |
| JP6572392B2 (ja) | 2019-09-11 |
| SG11201804936UA (en) | 2018-07-30 |
| US20190233406A1 (en) | 2019-08-01 |
| KR20180095598A (ko) | 2018-08-27 |
| AU2016370554A1 (en) | 2018-06-14 |
| TN2018000195A1 (en) | 2019-10-04 |
| WO2017106226A1 (en) | 2017-06-22 |
| AR106987A1 (es) | 2018-03-07 |
| CN108699015A (zh) | 2018-10-23 |
| JP2019502681A (ja) | 2019-01-31 |
| DOP2018000150A (es) | 2018-07-31 |
| ECSP18052850A (es) | 2018-12-31 |
| EA201891313A1 (ru) | 2018-11-30 |
| PE20181495A1 (es) | 2018-09-18 |
| SV2018005708A (es) | 2018-12-14 |
| NI201800067A (es) | 2018-07-24 |
| CO2018006137A2 (es) | 2018-07-10 |
| BR112018012327A2 (pt) | 2018-12-04 |
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