CN104968647B - 作为钠通道调节剂的酰胺 - Google Patents
作为钠通道调节剂的酰胺 Download PDFInfo
- Publication number
- CN104968647B CN104968647B CN201480006878.4A CN201480006878A CN104968647B CN 104968647 B CN104968647 B CN 104968647B CN 201480006878 A CN201480006878 A CN 201480006878A CN 104968647 B CN104968647 B CN 104968647B
- Authority
- CN
- China
- Prior art keywords
- another example
- alkyl
- halogen
- pain
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- 0 *c(c(*)c1)ccc1F Chemical compound *c(c(*)c1)ccc1F 0.000 description 5
- LJWAPDSCYTZUJU-UHFFFAOYSA-O COc(ccc([NH3+])c1)c1F Chemical compound COc(ccc([NH3+])c1)c1F LJWAPDSCYTZUJU-UHFFFAOYSA-O 0.000 description 1
- FRTZGCNYYJYILQ-UHFFFAOYSA-N COc1cc(F)ccc1Oc(cc(c(Cl)c1)Cl)c1C(Nc1ccnc(C(O)=O)c1)=O Chemical compound COc1cc(F)ccc1Oc(cc(c(Cl)c1)Cl)c1C(Nc1ccnc(C(O)=O)c1)=O FRTZGCNYYJYILQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary 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
- A61P25/04—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
-
- 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
- A61P9/06—Antiarrhythmics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/58—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/64—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361759062P | 2013-01-31 | 2013-01-31 | |
| US61/759,062 | 2013-01-31 | ||
| PCT/US2014/013667 WO2014120820A1 (en) | 2013-01-31 | 2014-01-29 | Amides as modulators of sodium channels |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104968647A CN104968647A (zh) | 2015-10-07 |
| CN104968647B true CN104968647B (zh) | 2018-01-26 |
Family
ID=50114569
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480006878.4A Active CN104968647B (zh) | 2013-01-31 | 2014-01-29 | 作为钠通道调节剂的酰胺 |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US9108903B2 (OSRAM) |
| EP (1) | EP2951155B1 (OSRAM) |
| JP (1) | JP6346622B2 (OSRAM) |
| KR (1) | KR102226588B1 (OSRAM) |
| CN (1) | CN104968647B (OSRAM) |
| AR (1) | AR094668A1 (OSRAM) |
| AU (1) | AU2014212431B2 (OSRAM) |
| BR (1) | BR112015018284B1 (OSRAM) |
| CA (1) | CA2898653C (OSRAM) |
| IL (1) | IL240196B (OSRAM) |
| MX (1) | MX359882B (OSRAM) |
| RU (1) | RU2658920C2 (OSRAM) |
| SG (1) | SG11201505954RA (OSRAM) |
| TW (1) | TWI659945B (OSRAM) |
| WO (1) | WO2014120820A1 (OSRAM) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102295748B1 (ko) | 2013-01-31 | 2021-09-01 | 버텍스 파마슈티칼스 인코포레이티드 | 나트륨 채널의 조절제로서의 피리돈 아미드 |
| EP2951168B1 (en) | 2013-01-31 | 2017-01-04 | Vertex Pharmaceuticals Incorporated | Quinoline and quinoxaline amides as modulators of sodium channels |
| JP6337109B2 (ja) | 2013-07-19 | 2018-06-06 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | ナトリウムチャネルの調節剤としてのスルホンアミド |
| TWI703154B (zh) | 2013-12-13 | 2020-09-01 | 美商維泰克斯製藥公司 | 作為鈉通道調節劑之吡啶酮醯胺之前藥 |
| UA124857C2 (uk) | 2017-05-16 | 2021-12-01 | Вертекс Фармасьютикалз Інкорпорейтед | Дейтеровані піридонаміди і їх проліки як модулятори натрієвих каналів |
| UY37806A (es) | 2017-07-11 | 2020-01-31 | Vertex Pharma | Carboxamidas como moduladores de los canales de sodio |
| EP3752152A1 (en) | 2018-02-12 | 2020-12-23 | Vertex Pharmaceuticals Incorporated | A method of treating pain |
| EP3873468A4 (en) | 2018-11-02 | 2022-10-26 | Merck Sharp & Dohme LLC | 2-AMINO-N-PHENYL-NICOTINAMIDES AS NAV1.8 INHIBITORS |
| KR102812202B1 (ko) | 2018-11-02 | 2025-05-23 | 머크 샤프 앤드 돔 엘엘씨 | Nav1.8 억제제로서의 2-아미노-n-헤테로아릴-니코틴아미드 |
| EP3907218A4 (en) * | 2019-01-04 | 2022-09-21 | Jiangsu Hengrui Medicine Co., Ltd. | 6-OXO-1,6-DIHYDROPYRIDAZINE DERIVATIVE, METHOD FOR PREPARATION AND MEDICAL USE |
| US12441703B2 (en) | 2019-01-10 | 2025-10-14 | Vertex Pharmaceuticals Incorporated | Carboxamides as modulators of sodium channels |
| WO2020146612A1 (en) | 2019-01-10 | 2020-07-16 | Vertex Pharmaceuticals Incorporated | Esters and carbamates as modulators of sodium channels |
| BR112021014178A2 (pt) * | 2019-02-20 | 2021-09-21 | Jiangsu Hengrui Medicine Co., Ltd. | Derivado de pró-fármaco de 6-oxo-1,6-diidropiridazina, método de preparação para o mesmo e aplicação do mesmo na medicina |
| WO2020176763A1 (en) | 2019-02-27 | 2020-09-03 | Vertex Pharmaceuticals Incorporated | Dosage form comprising prodrug of na 1.8 sodium channel inhibitor |
| WO2020219867A1 (en) | 2019-04-25 | 2020-10-29 | Vertex Pharmaceuticals Incorporated | Pyridone amide co-crystal compositions for the treatment of pain |
| CA3150400A1 (en) * | 2019-09-12 | 2021-03-18 | Shanghai Jemincare Pharmaceuticals Co., Ltd | Pyridine oxynitride, preparation method therefor and use thereof |
| HUE069128T2 (hu) | 2019-12-06 | 2025-02-28 | Vertex Pharma | Szubsztituált tetrahidrofurán vegyületek mint nátriumcsatornák modulátorai |
| CN114437062B (zh) * | 2020-04-30 | 2024-05-17 | 成都海博为药业有限公司 | 一种可作为钠通道调节剂的化合物及其用途 |
| JP7323723B2 (ja) | 2020-06-17 | 2023-08-08 | メルク・シャープ・アンド・ドーム・エルエルシー | Ｎａｖ１．８阻害剤としての２－オキソイミダゾリジン－４－カルボキサミド |
| CN113880771B (zh) * | 2020-07-03 | 2023-09-19 | 福建盛迪医药有限公司 | 一种选择性Nav抑制剂的结晶形式及其制备方法 |
| CN114031518B (zh) * | 2020-12-08 | 2023-08-18 | 成都海博为药业有限公司 | 一种苄胺或苄醇衍生物及其用途 |
| CN112225695B (zh) * | 2020-12-15 | 2021-03-02 | 上海济煜医药科技有限公司 | 一种氮氧化合物及其制备方法和用途 |
| WO2022188872A1 (zh) * | 2021-03-11 | 2022-09-15 | 上海济煜医药科技有限公司 | 吡啶氮氧化合物晶型及其应用 |
| KR20240005878A (ko) | 2021-05-07 | 2024-01-12 | 머크 샤프 앤드 돔 엘엘씨 | Nav1.8 억제제로서의 시클로알킬 3-옥소피페라진 카르복스아미드 및 시클로헤테로알킬 3-옥소피페라진 카르복스아미드 |
| AU2022284886A1 (en) | 2021-06-04 | 2023-11-30 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamides as modulators of sodium channels |
| CN117794918A (zh) | 2021-06-04 | 2024-03-29 | 沃泰克斯药物股份有限公司 | 经取代的四氢呋喃类似物作为钠通道调节剂 |
| US20240285596A1 (en) | 2021-06-04 | 2024-08-29 | Vertex Pharmaceuticals Incorporated | Solid dosage forms and dosing regimens comprising (2r,3s,4s,5r)-4-[[3-(3,4-difluoro-2-methoxy-phenyl)-4,5-dimethyl-5-(trifluoromethyl) tetrahydrofuran-2-carbonyl]amino]pyridine-2-carboxamide |
| US20240294512A1 (en) | 2021-06-04 | 2024-09-05 | Vertex Pharmaceuticals Incorporated | Hydroxy and (halo)alkoxy substituted tetrahydrofurans as modulators of sodium channels |
| US20240368135A1 (en) | 2021-06-04 | 2024-11-07 | Vertex Pharmaceuticals Incorporated | Substituted tetrahydrofuran-2-carboxamides as modulators of sodium channels |
| US20240400544A1 (en) | 2021-06-04 | 2024-12-05 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamide analogs as modulators of sodium channels |
| AU2023255558A1 (en) | 2022-04-22 | 2024-10-31 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| TW202404969A (zh) | 2022-04-22 | 2024-02-01 | 美商維泰克斯製藥公司 | 用於治療疼痛之雜芳基化合物 |
| JP2025513454A (ja) | 2022-04-22 | 2025-04-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | 疼痛の治療のためのヘテロアリール化合物 |
| CN119522214A (zh) | 2022-04-22 | 2025-02-25 | 沃泰克斯药物股份有限公司 | 用于治疗疼痛的杂芳基化合物 |
| WO2023211990A1 (en) | 2022-04-25 | 2023-11-02 | Siteone Therapeutics, Inc. | Bicyclic heterocyclic amide inhibitors of na v1.8 for the treatment of pain |
| KR20250120351A (ko) | 2022-12-06 | 2025-08-08 | 버텍스 파마슈티칼스 인코포레이티드 | 나트륨 채널의 치환된 테트라하이드로푸란 조절제의 합성을 위한 방법 |
| TW202434235A (zh) * | 2023-01-18 | 2024-09-01 | 芬蘭商奧利安公司 | ３－（４，５－二氯－２－（４－（三氟甲氧基）苯氧基）苯甲醯胺基）吡啶１－氧化物的製備方法 |
| TW202523313A (zh) | 2023-10-23 | 2025-06-16 | 美商維泰克斯製藥公司 | 用於治療疼痛之雜芳基化合物 |
| WO2025090516A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Methods of preparing compounds for treating pain and solid forms thereof |
| WO2025090480A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| WO2025090511A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Methods of preparing modulators of sodium channels and solid forms of the same for treating pain |
| US20250186419A1 (en) | 2023-12-07 | 2025-06-12 | Vertex Pharmaceuticals Incorporated | Dosing regimens for treating pain |
| WO2025160286A1 (en) | 2024-01-24 | 2025-07-31 | Siteone Therapeutics, Inc. | 2-aryl cycloalkyl and heterocycloalkyl inhibitors of nav1.8 for the treatment of pain |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101855210A (zh) * | 2007-10-11 | 2010-10-06 | 沃泰克斯药物股份有限公司 | 用作电压-门控钠通道抑制剂的酰胺类 |
| CN101883758A (zh) * | 2007-10-11 | 2010-11-10 | 沃泰克斯药物股份有限公司 | 用作电压门控的钠通道抑制剂的芳基酰胺类化合物 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2511231A (en) * | 1949-03-26 | 1950-06-13 | Eastman Kodak Co | 1-cyanophenyl-3-acylamino-5-pyrazolone couplers for color photography |
| US8841483B2 (en) | 2006-04-11 | 2014-09-23 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of voltage-gated sodium channels |
| US8519137B2 (en) | 2007-10-11 | 2013-08-27 | Vertex Pharmaceuticals Incorporated | Heteroaryl amides useful as inhibitors of voltage-gated sodium channels |
| CN105254557A (zh) * | 2009-05-29 | 2016-01-20 | 拉夸里亚创药株式会社 | 作为钙或钠通道阻滞剂的芳基取代羧酰胺衍生物 |
-
2014
- 2014-01-29 EP EP14704981.1A patent/EP2951155B1/en active Active
- 2014-01-29 WO PCT/US2014/013667 patent/WO2014120820A1/en not_active Ceased
- 2014-01-29 US US14/167,741 patent/US9108903B2/en active Active
- 2014-01-29 AU AU2014212431A patent/AU2014212431B2/en active Active
- 2014-01-29 AR ARP140100282A patent/AR094668A1/es unknown
- 2014-01-29 CN CN201480006878.4A patent/CN104968647B/zh active Active
- 2014-01-29 BR BR112015018284-4A patent/BR112015018284B1/pt not_active IP Right Cessation
- 2014-01-29 MX MX2015009591A patent/MX359882B/es active IP Right Grant
- 2014-01-29 CA CA2898653A patent/CA2898653C/en active Active
- 2014-01-29 JP JP2015556113A patent/JP6346622B2/ja active Active
- 2014-01-29 RU RU2015136779A patent/RU2658920C2/ru active
- 2014-01-29 KR KR1020157023600A patent/KR102226588B1/ko not_active Expired - Fee Related
- 2014-01-29 TW TW103103690A patent/TWI659945B/zh active
- 2014-01-29 SG SG11201505954RA patent/SG11201505954RA/en unknown
-
2015
- 2015-07-27 US US14/809,841 patent/US9421196B2/en active Active
- 2015-07-28 IL IL240196A patent/IL240196B/en active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101855210A (zh) * | 2007-10-11 | 2010-10-06 | 沃泰克斯药物股份有限公司 | 用作电压-门控钠通道抑制剂的酰胺类 |
| CN101883758A (zh) * | 2007-10-11 | 2010-11-10 | 沃泰克斯药物股份有限公司 | 用作电压门控的钠通道抑制剂的芳基酰胺类化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201443005A (zh) | 2014-11-16 |
| BR112015018284A2 (pt) | 2017-07-18 |
| WO2014120820A9 (en) | 2015-07-02 |
| IL240196B (en) | 2019-08-29 |
| KR102226588B1 (ko) | 2021-03-11 |
| US9421196B2 (en) | 2016-08-23 |
| AU2014212431A1 (en) | 2015-08-06 |
| JP6346622B2 (ja) | 2018-06-20 |
| TWI659945B (zh) | 2019-05-21 |
| AR094668A1 (es) | 2015-08-19 |
| HK1217692A1 (en) | 2017-01-20 |
| US9108903B2 (en) | 2015-08-18 |
| CA2898653A1 (en) | 2014-08-07 |
| JP2016508500A (ja) | 2016-03-22 |
| KR20150118964A (ko) | 2015-10-23 |
| CA2898653C (en) | 2021-09-28 |
| AU2014212431B2 (en) | 2018-04-05 |
| RU2658920C2 (ru) | 2018-06-26 |
| MX2015009591A (es) | 2016-04-15 |
| WO2014120820A1 (en) | 2014-08-07 |
| SG11201505954RA (en) | 2015-08-28 |
| CN104968647A (zh) | 2015-10-07 |
| BR112015018284B1 (pt) | 2023-03-07 |
| US20150328196A1 (en) | 2015-11-19 |
| EP2951155B1 (en) | 2019-06-19 |
| IL240196A0 (en) | 2015-09-24 |
| EP2951155A1 (en) | 2015-12-09 |
| US20140221435A1 (en) | 2014-08-07 |
| NZ710293A (en) | 2020-09-25 |
| MX359882B (es) | 2018-10-15 |
| RU2015136779A (ru) | 2017-03-07 |
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