TWI659945B - 作爲鈉通道調節劑之醯胺 - Google Patents
作爲鈉通道調節劑之醯胺 Download PDFInfo
- Publication number
- TWI659945B TWI659945B TW103103690A TW103103690A TWI659945B TW I659945 B TWI659945 B TW I659945B TW 103103690 A TW103103690 A TW 103103690A TW 103103690 A TW103103690 A TW 103103690A TW I659945 B TWI659945 B TW I659945B
- Authority
- TW
- Taiwan
- Prior art keywords
- another embodiment
- alkyl
- pain
- benzylidene
- halogen
- Prior art date
Links
- SCVAJTQTAYTWBF-UHFFFAOYSA-N CC(C)Oc(cccc1)c1Oc(ccc(C(F)(F)F)c1)c1C(Nc1ccc(C(O)=O)nc1)=O Chemical compound CC(C)Oc(cccc1)c1Oc(ccc(C(F)(F)F)c1)c1C(Nc1ccc(C(O)=O)nc1)=O SCVAJTQTAYTWBF-UHFFFAOYSA-N 0.000 description 1
- JPVADBDXDGHZBJ-UHFFFAOYSA-N COc(cc(cc1)F)c1Oc(cc(c(Cl)c1)Cl)c1C(Nc(cc1)ccc1C(O)=O)=O Chemical compound COc(cc(cc1)F)c1Oc(cc(c(Cl)c1)Cl)c1C(Nc(cc1)ccc1C(O)=O)=O JPVADBDXDGHZBJ-UHFFFAOYSA-N 0.000 description 1
- BQNMADFVJFWVJU-UHFFFAOYSA-N COc(cccc1)c1Oc1ccc(C(F)(F)F)cc1C(Nc1ccc(C(O)=O)nc1)=O Chemical compound COc(cccc1)c1Oc1ccc(C(F)(F)F)cc1C(Nc1ccc(C(O)=O)nc1)=O BQNMADFVJFWVJU-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)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361759062P | 2013-01-31 | 2013-01-31 | |
| US61/759,062 | 2013-01-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201443005A TW201443005A (zh) | 2014-11-16 |
| TWI659945B true TWI659945B (zh) | 2019-05-21 |
Family
ID=50114569
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW103103690A TWI659945B (zh) | 2013-01-31 | 2014-01-29 | 作爲鈉通道調節劑之醯胺 |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US9108903B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2951155B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP6346622B2 (cg-RX-API-DMAC7.html) |
| KR (1) | KR102226588B1 (cg-RX-API-DMAC7.html) |
| CN (1) | CN104968647B (cg-RX-API-DMAC7.html) |
| AR (1) | AR094668A1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU2014212431B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BR112015018284B1 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2898653C (cg-RX-API-DMAC7.html) |
| IL (1) | IL240196B (cg-RX-API-DMAC7.html) |
| MX (1) | MX359882B (cg-RX-API-DMAC7.html) |
| RU (1) | RU2658920C2 (cg-RX-API-DMAC7.html) |
| SG (1) | SG11201505954RA (cg-RX-API-DMAC7.html) |
| TW (1) | TWI659945B (cg-RX-API-DMAC7.html) |
| WO (1) | WO2014120820A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR095192A1 (es) | 2013-01-31 | 2015-09-30 | Vertex Pharma | Quinolina y quinazolinamidas como modulares de canales de sodio |
| AR094667A1 (es) | 2013-01-31 | 2015-08-19 | Vertex Pharma | Piridonamidas como moduladores de canales de sodio |
| CA2918365C (en) | 2013-07-19 | 2021-09-07 | Vertex Pharmaceuticals Incorporated | Sulfonamides as modulators of sodium channels |
| UA121379C2 (uk) | 2013-12-13 | 2020-05-25 | Вертекс Фармасьютикалз Інкорпорейтед | Проліки піридонамідів, застосовувані як модулятори натрієвих каналів |
| JP7104070B2 (ja) | 2017-05-16 | 2022-07-20 | 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 | ナトリウムチャネルの調節因子としての重水素化ピリドンアミドおよびそのプロドラッグ |
| ES3008911T3 (en) | 2017-07-11 | 2025-03-25 | Vertex Pharma | Carboxamides as modulators of sodium channels |
| US20190343817A1 (en) | 2018-02-12 | 2019-11-14 | Vertex Pharmaceuticals Incorporated | 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 |
| JOP20210097A1 (ar) * | 2018-11-02 | 2023-01-30 | Merck Sharp & Dohme | مركبات 2-أمينو-n-أريل غير متجانس-نيكوتيناميد كمثبطات nav1.8 |
| CA3125244A1 (en) * | 2019-01-04 | 2020-07-09 | Jiangsu Hengrui Medicine Co., Ltd. | 6-oxo-1,6-dihydropyridazine derivative, preparation method therefor and medical use thereof |
| WO2020146612A1 (en) | 2019-01-10 | 2020-07-16 | Vertex Pharmaceuticals Incorporated | Esters and carbamates as modulators of sodium channels |
| US12441703B2 (en) | 2019-01-10 | 2025-10-14 | Vertex Pharmaceuticals Incorporated | Carboxamides as modulators of sodium channels |
| US20220162169A1 (en) * | 2019-02-20 | 2022-05-26 | Jiangsu Hengrui Medicine Co., Ltd. | 6-oxo-1,6-dihydropyridazine prodrug derivative, preparation method therefor, and application thereof in medicine |
| 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 |
| JP2022548104A (ja) * | 2019-09-12 | 2022-11-16 | オリオン コーポレーション | ピリジン窒素酸化物及びその製造方法と使用 |
| SI4069691T1 (sl) * | 2019-12-06 | 2025-02-28 | Vertex Pharmaceuticals Incorporated | Substituirani tetrahidrofurani kot modulatorji natrijevih kanalčkov |
| 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 |
| MX2022015581A (es) | 2020-06-17 | 2023-01-24 | Merck Sharp & Dohme Llc | 2-oxoimidazolidin-4-carboxamidas como inhibidores de nav1.8. |
| 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 |
| MX2023010704A (es) * | 2021-03-11 | 2023-12-07 | Shanghai Jemincare Pharmaceuticals Co Ltd | Forma cristalina de un compuesto de oxido de nitrogeno de piridina y uso de la misma. |
| BR112023023239A2 (pt) | 2021-05-07 | 2024-01-23 | Merck Sharp & Dohme Llc | Carboxamidas de cicloalquil 3-oxopiperazina e carboxamidas de cicloheteroalquil 3-oxopiperazina como inibidores de nav1.8 |
| WO2022256679A1 (en) | 2021-06-04 | 2022-12-08 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamide analogs as modulators of sodium channels |
| JP2024520648A (ja) | 2021-06-04 | 2024-05-24 | 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 | ナトリウムチャネルの調節因子としての置換テトラヒドロフラン－２－カルボキサミド |
| CA3221960A1 (en) | 2021-06-04 | 2022-12-08 | Vertex Pharmaceuticals Incorporated | Hydroxy and (halo)alkoxy substituted tetrahydrofurans as modulators of sodium channels |
| EP4347031B1 (en) | 2021-06-04 | 2025-10-29 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamides as modulators of sodium channels |
| 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 |
| 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 |
| AU2023257313A1 (en) | 2022-04-22 | 2024-10-31 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| CN119487003A (zh) | 2022-04-22 | 2025-02-18 | 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 |
| CR20240513A (es) | 2022-04-22 | 2025-04-30 | Vertex Pharma | Compuestos de heteroarilo para el tratamiento del dolor |
| EP4511114A1 (en) | 2022-04-22 | 2025-02-26 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| KR20250006217A (ko) | 2022-04-25 | 2025-01-10 | 사이트원 테라퓨틱스, 인코포레이티드 | 통증 치료를 위한 Naν1.8의 바이사이클릭 헤테로사이클릭 아미드 억제제 |
| EP4630405A1 (en) | 2022-12-06 | 2025-10-15 | Vertex Pharmaceuticals Incorporated | Process for the synthesis of substituted tetrahydrofuran modulators of sodium channels |
| WO2024153856A1 (en) * | 2023-01-18 | 2024-07-25 | Orion Corporation | Process for the preparation of 3-(4,5-dichloro-2-(4-(trifluoromethoxy)phenoxy)benzamido)pyridine 1-oxide |
| TW202535867A (zh) | 2023-10-23 | 2025-09-16 | 美商維泰克斯製藥公司 | 用於治療疼痛之鈉通道調節劑及其固體形式的製備方法 |
| WO2025090480A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| WO2025090516A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Methods of preparing compounds for treating pain and solid forms thereof |
| 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 |
| 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 (1)
| 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 |
Family Cites Families (5)
| 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 |
| MX2008013194A (es) | 2006-04-11 | 2008-12-01 | Vertex Pharma | Composiciones utiles como inhibidores de canales de sodio regulados por voltaje. |
| US8779197B2 (en) * | 2007-10-11 | 2014-07-15 | Vertex Pharmaceuticals Incorporated | Aryl amides 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 |
| EP2435407B1 (en) * | 2009-05-29 | 2019-12-25 | RaQualia Pharma Inc. | Aryl substituted carboxamide derivatives as calcium or sodium channel blockers |
-
2014
- 2014-01-29 US US14/167,741 patent/US9108903B2/en active Active
- 2014-01-29 AR ARP140100282A patent/AR094668A1/es unknown
- 2014-01-29 BR BR112015018284-4A patent/BR112015018284B1/pt not_active IP Right Cessation
- 2014-01-29 CN CN201480006878.4A patent/CN104968647B/zh active Active
- 2014-01-29 SG SG11201505954RA patent/SG11201505954RA/en unknown
- 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 MX MX2015009591A patent/MX359882B/es active IP Right Grant
- 2014-01-29 WO PCT/US2014/013667 patent/WO2014120820A1/en not_active Ceased
- 2014-01-29 RU RU2015136779A patent/RU2658920C2/ru active
- 2014-01-29 AU AU2014212431A patent/AU2014212431B2/en active Active
- 2014-01-29 JP JP2015556113A patent/JP6346622B2/ja active Active
- 2014-01-29 EP EP14704981.1A patent/EP2951155B1/en active Active
- 2014-01-29 CA CA2898653A patent/CA2898653C/en active Active
-
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 (1)
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR102226588B1 (ko) | 2021-03-11 |
| MX359882B (es) | 2018-10-15 |
| WO2014120820A9 (en) | 2015-07-02 |
| AU2014212431A1 (en) | 2015-08-06 |
| US20140221435A1 (en) | 2014-08-07 |
| BR112015018284B1 (pt) | 2023-03-07 |
| US9421196B2 (en) | 2016-08-23 |
| BR112015018284A2 (pt) | 2017-07-18 |
| JP6346622B2 (ja) | 2018-06-20 |
| RU2015136779A (ru) | 2017-03-07 |
| CN104968647A (zh) | 2015-10-07 |
| WO2014120820A1 (en) | 2014-08-07 |
| MX2015009591A (es) | 2016-04-15 |
| JP2016508500A (ja) | 2016-03-22 |
| SG11201505954RA (en) | 2015-08-28 |
| US20150328196A1 (en) | 2015-11-19 |
| IL240196B (en) | 2019-08-29 |
| CA2898653C (en) | 2021-09-28 |
| EP2951155A1 (en) | 2015-12-09 |
| IL240196A0 (en) | 2015-09-24 |
| TW201443005A (zh) | 2014-11-16 |
| KR20150118964A (ko) | 2015-10-23 |
| AU2014212431B2 (en) | 2018-04-05 |
| AR094668A1 (es) | 2015-08-19 |
| EP2951155B1 (en) | 2019-06-19 |
| CN104968647B (zh) | 2018-01-26 |
| CA2898653A1 (en) | 2014-08-07 |
| RU2658920C2 (ru) | 2018-06-26 |
| US9108903B2 (en) | 2015-08-18 |
| NZ710293A (en) | 2020-09-25 |
| HK1217692A1 (en) | 2017-01-20 |
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