MX337477B - Derivados de diaminopiridina y procesos para su preparacion. - Google Patents
Derivados de diaminopiridina y procesos para su preparacion.Info
- Publication number
- MX337477B MX337477B MX2013009549A MX2013009549A MX337477B MX 337477 B MX337477 B MX 337477B MX 2013009549 A MX2013009549 A MX 2013009549A MX 2013009549 A MX2013009549 A MX 2013009549A MX 337477 B MX337477 B MX 337477B
- Authority
- MX
- Mexico
- Prior art keywords
- preparation
- pharmaceutically acceptable
- acceptable salt
- processes
- diaminopyrimidine derivative
- Prior art date
Links
- MISVBCMQSJUHMH-UHFFFAOYSA-N pyrimidine-4,6-diamine Chemical class NC1=CC(N)=NC=N1 MISVBCMQSJUHMH-UHFFFAOYSA-N 0.000 title abstract 3
- 238000000034 method Methods 0.000 title abstract 2
- 238000002360 preparation method Methods 0.000 title abstract 2
- 206010021518 Impaired gastric emptying Diseases 0.000 abstract 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 abstract 2
- 208000002551 irritable bowel syndrome Diseases 0.000 abstract 2
- 150000003839 salts Chemical class 0.000 abstract 2
- 108091005482 5-HT4 receptors Proteins 0.000 abstract 1
- 206010010774 Constipation Diseases 0.000 abstract 1
- 206010017753 Gastric atony Diseases 0.000 abstract 1
- 208000018522 Gastrointestinal disease Diseases 0.000 abstract 1
- 206010052105 Gastrointestinal hypomotility Diseases 0.000 abstract 1
- 201000005081 Intestinal Pseudo-Obstruction Diseases 0.000 abstract 1
- 206010054048 Postoperative ileus Diseases 0.000 abstract 1
- 230000003111 delayed effect Effects 0.000 abstract 1
- 206010012601 diabetes mellitus Diseases 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 230000004064 dysfunction Effects 0.000 abstract 1
- 201000006549 dyspepsia Diseases 0.000 abstract 1
- 230000005176 gastrointestinal motility Effects 0.000 abstract 1
- 208000001288 gastroparesis Diseases 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 239000000018 receptor agonist Substances 0.000 abstract 1
- 229940044601 receptor agonist Drugs 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P1/10—Laxatives
-
- 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
- A61P1/12—Antidiarrhoeals
-
- 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
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
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)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nutrition Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20110016981 | 2011-02-25 | ||
| PCT/KR2012/001427 WO2012115480A2 (en) | 2011-02-25 | 2012-02-24 | Diaminopyrimidine derivatives and processes for the preparation thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| MX2013009549A MX2013009549A (es) | 2013-09-06 |
| MX337477B true MX337477B (es) | 2016-03-07 |
Family
ID=46721361
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2013009549A MX337477B (es) | 2011-02-25 | 2012-02-24 | Derivados de diaminopiridina y procesos para su preparacion. |
| MX2013009627A MX336155B (es) | 2011-02-25 | 2012-02-24 | Derivados de diaminopirimidina y procesos para su preparacion. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2013009627A MX336155B (es) | 2011-02-25 | 2012-02-24 | Derivados de diaminopirimidina y procesos para su preparacion. |
Country Status (17)
| Country | Link |
|---|---|
| US (4) | US9890138B2 (enExample) |
| EP (2) | EP2678332B1 (enExample) |
| JP (2) | JP5890436B2 (enExample) |
| KR (2) | KR101671341B1 (enExample) |
| CN (2) | CN103402997B (enExample) |
| AU (2) | AU2012221927B2 (enExample) |
| BR (2) | BR112013019942B1 (enExample) |
| CA (2) | CA2827030C (enExample) |
| DK (1) | DK2678332T3 (enExample) |
| ES (2) | ES2587304T3 (enExample) |
| HU (1) | HUE029988T2 (enExample) |
| IN (1) | IN2013MN01519A (enExample) |
| MX (2) | MX337477B (enExample) |
| PL (2) | PL2678331T3 (enExample) |
| PT (1) | PT2678332T (enExample) |
| RU (1) | RU2587493C2 (enExample) |
| WO (2) | WO2012115480A2 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103402997B (zh) * | 2011-02-25 | 2015-08-26 | 柳韩洋行 | 二氨基嘧啶衍生物及其制备方法 |
| JP6412503B2 (ja) | 2012-11-21 | 2018-10-24 | ピーティーシー セラピューティクス， インコーポレイテッド | 置換逆ピリミジンＢｍｉ−１阻害剤 |
| KR101657616B1 (ko) * | 2013-05-24 | 2016-09-19 | 주식회사유한양행 | 피리미딘 고리를 포함하는 바이사이클릭 유도체 및 그의 제조방법 |
| KR102232595B1 (ko) | 2013-08-30 | 2021-03-26 | 피티씨 테라퓨틱스, 인크. | 치환된 피리미딘 bmi-1 저해제 |
| EP3071553A4 (en) | 2013-11-21 | 2017-08-02 | PTC Therapeutics, Inc. | Substituted pyridine and pyrazine bmi-1 inhibitors |
| CN104003944B (zh) * | 2014-05-29 | 2016-08-24 | 西北师范大学 | 一种嘧菌胺的制备方法 |
| NZ730012A (en) * | 2014-10-13 | 2019-06-28 | Yuhan Corp | Compounds and compositions for modulating egfr mutant kinase activities |
| US10300155B2 (en) | 2015-12-31 | 2019-05-28 | Washington University | Alpha-synuclein ligands |
| CN105646321A (zh) * | 2016-01-07 | 2016-06-08 | 中国药科大学 | (s)-3-羟基吡咯烷盐酸盐的制备方法 |
| GB201604647D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| KR102441327B1 (ko) | 2018-05-18 | 2022-09-07 | 주식회사유한양행 | 다이아미노피리미딘 유도체 또는 이의 산부가염의 신규의 제조방법 |
| JP2021535198A (ja) | 2018-08-17 | 2021-12-16 | ピーティーシー セラピューティクス， インコーポレイテッド | 膵臓癌を治療する方法 |
| CN118834204A (zh) | 2018-12-18 | 2024-10-25 | 阿斯利康(瑞典)有限公司 | 制药方法和中间体 |
| CN110317176A (zh) * | 2019-07-04 | 2019-10-11 | 沈阳药科大学 | 2-氨基嘧啶类化合物及其用途 |
| KR20220006776A (ko) * | 2020-07-09 | 2022-01-18 | 주식회사유한양행 | 다이아미노피리미딘 유도체 또는 이의 약학적으로 허용가능한 염을 포함하는 약학 조성물 및 이의 제조방법 |
| WO2025104079A1 (en) * | 2023-11-17 | 2025-05-22 | Helmholtz-Zentrum für Infektionsforschung GmbH | Salicylic acid and picolinic acid derivatives as inhibitors of energy coupling factor (ecf) transporters for the treatment of bacterial infections |
| WO2026061469A1 (zh) * | 2024-09-19 | 2026-03-26 | 马应龙药业集团股份有限公司 | 杂芳胺类化合物、其药物组合物及其应用 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4962115A (en) | 1981-10-01 | 1990-10-09 | Janssen Pharmaceutica N.V. | Novel N-(3-hydroxy-4-piperidinyl)benzamide derivatives |
| CZ284687B6 (cs) | 1986-04-30 | 1999-02-17 | Dainippon Pharmaceutical Co., Ltd. | Substituovaný benzamidový derivát, způsob jeho výroby a farmaceutický prostředek na jeho bázi |
| GB9005014D0 (en) | 1990-03-06 | 1990-05-02 | Janssen Pharmaceutica Nv | N.(4.piperidinyl)(dihydrobenzofuran or dihydro.2h.benzopyran)carboxamide derivatives |
| HUT64023A (en) | 1991-03-22 | 1993-11-29 | Sandoz Ag | Process for producing aminoguanidine derivatives and pharmaceutical compositions comprising such compounds |
| CA2174080A1 (en) * | 1993-10-12 | 1995-04-20 | Paul Edward Aldrich | 1n-alkyl-n-arylpyrimidinamines and derivatives thereof |
| JP3398152B2 (ja) * | 1993-10-12 | 2003-04-21 | ブリストル‐マイヤーズ・スクイブ・ファーマ・カンパニー | １ｎ−アルキル−ｎ−アリールピリミジンアミンおよびその誘導体 |
| IL112024A (en) * | 1993-12-21 | 1999-07-14 | Novo Nordisk As | Pharmaceutical compositions comprising tetrahydropyridine derivatives substituted with oxadiazole or thiadiazole for treating gastrointestinal motility disorders |
| AU688087B2 (en) | 1994-08-13 | 1998-03-05 | Yuhan Corporation | Novel pyrimidine derivatives and processes for the preparation thereof |
| US5739151A (en) * | 1996-07-19 | 1998-04-14 | Sepracor Inc. | Method for treating emesis and central nervous system disorders using optically pure (+) norcisapride |
| IN188411B (enExample) * | 1997-03-27 | 2002-09-21 | Yuhan Corp | |
| US6825198B2 (en) * | 2001-06-21 | 2004-11-30 | Pfizer Inc | 5-HT receptor ligands and uses thereof |
| MXPA06000771A (es) * | 2003-07-25 | 2006-04-18 | Ciba Sc Holding Ag | Uso de 2,4-bis(alquilamino)-pirimidinas o -quinazolinas substituidas como antimicrobianos. |
| JP2007507425A (ja) * | 2003-08-29 | 2007-03-29 | ダイノゲン ファーマシューティカルズ，インコーポレイテッド | 胃腸管運動障害を処置するために有用な組成物 |
| US20060057972A1 (en) | 2004-09-14 | 2006-03-16 | Wikel Harold L | Adapter for a modular wireless communication device |
| US20060128726A1 (en) | 2004-11-24 | 2006-06-15 | Xuebao Wang | Process for preparing novel crystalline forms of (2S)-1-[[(7R)-7-(3,4-dichlorophenyl)-4,7-dihydro-5-methylpyrazolo[1,5]pyrimidine-6-yl]carbonyl]-2-(4-fluorophenyl)pyrrolidine, novel stable forms produced therein and formulations |
| WO2006090224A1 (en) * | 2005-02-25 | 2006-08-31 | Pfizer Japan Inc. | Benzisoxazole derivatives |
| US20070032514A1 (en) * | 2005-07-01 | 2007-02-08 | Zahn Stephan K | 2,4-diamino-pyrimidines as aurora inhibitors |
| US20080293942A1 (en) | 2005-11-28 | 2008-11-27 | Cousins Russell D | Methods of Preparing 2-Imidazol-1-Yl-4-Methyl-6-Pyrrolidin-2-Yl-Pyrimidine and 4-(1-Alkylpyrrolidin-2-Yl)-2-(1H-Imidazol-1-Yl)-6-Methylpyrimidine Derivatives |
| US8044068B2 (en) * | 2006-04-04 | 2011-10-25 | Taisho Pharmaceutical Co., Ltd | Aminopyrrolidine compound |
| CA2648170A1 (en) * | 2006-04-10 | 2007-10-18 | Boehringer Ingelheim International Gmbh | 2, 4-diaminopyrimidine derivatives and their use for the treatment of cancer |
| AU2009216851B2 (en) * | 2008-02-22 | 2013-11-07 | F. Hoffmann-La Roche Ag | Modulators for amyloid beta |
| JP5918693B2 (ja) * | 2009-05-05 | 2016-05-18 | ダナ ファーバー キャンサー インスティテュート インコーポレイテッド | Ｅｇｆｒ阻害剤及び疾患の治療方法 |
| CN103402997B (zh) * | 2011-02-25 | 2015-08-26 | 柳韩洋行 | 二氨基嘧啶衍生物及其制备方法 |
-
2012
- 2012-02-24 CN CN201280010406.7A patent/CN103402997B/zh active Active
- 2012-02-24 ES ES12750114.6T patent/ES2587304T3/es active Active
- 2012-02-24 IN IN1519MUN2013 patent/IN2013MN01519A/en unknown
- 2012-02-24 US US14/001,489 patent/US9890138B2/en active Active
- 2012-02-24 DK DK12750114.6T patent/DK2678332T3/en active
- 2012-02-24 EP EP12750114.6A patent/EP2678332B1/en active Active
- 2012-02-24 KR KR1020120018926A patent/KR101671341B1/ko active Active
- 2012-02-24 JP JP2013555369A patent/JP5890436B2/ja active Active
- 2012-02-24 CA CA2827030A patent/CA2827030C/en active Active
- 2012-02-24 US US14/001,475 patent/US9850227B2/en active Active
- 2012-02-24 KR KR1020120018933A patent/KR101671348B1/ko active Active
- 2012-02-24 MX MX2013009549A patent/MX337477B/es active IP Right Grant
- 2012-02-24 CA CA2827072A patent/CA2827072C/en active Active
- 2012-02-24 WO PCT/KR2012/001427 patent/WO2012115480A2/en not_active Ceased
- 2012-02-24 AU AU2012221927A patent/AU2012221927B2/en active Active
- 2012-02-24 BR BR112013019942-3A patent/BR112013019942B1/pt active IP Right Grant
- 2012-02-24 PL PL12749916.8T patent/PL2678331T3/pl unknown
- 2012-02-24 RU RU2013142187/04A patent/RU2587493C2/ru active
- 2012-02-24 ES ES12749916.8T patent/ES2579830T3/es active Active
- 2012-02-24 MX MX2013009627A patent/MX336155B/es unknown
- 2012-02-24 EP EP12749916.8A patent/EP2678331B1/en active Active
- 2012-02-24 CN CN201280010354.3A patent/CN103391935B/zh active Active
- 2012-02-24 HU HUE12750114A patent/HUE029988T2/en unknown
- 2012-02-24 PL PL12750114.6T patent/PL2678332T3/pl unknown
- 2012-02-24 WO PCT/KR2012/001423 patent/WO2012115478A2/en not_active Ceased
- 2012-02-24 PT PT127501146T patent/PT2678332T/pt unknown
- 2012-02-24 BR BR112013020641-1A patent/BR112013020641B1/pt active IP Right Grant
- 2012-02-24 AU AU2012221925A patent/AU2012221925B2/en active Active
- 2012-02-24 JP JP2013555368A patent/JP5980236B2/ja active Active
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2017
- 2017-11-15 US US15/813,741 patent/US10640490B2/en active Active
- 2017-12-20 US US15/848,760 patent/US10227330B2/en active Active
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