JP5701750B2 - 肝保護剤アセトアミノフェンミューチュアルプロドラッグ - Google Patents
肝保護剤アセトアミノフェンミューチュアルプロドラッグ Download PDFInfo
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- JP5701750B2 JP5701750B2 JP2011510694A JP2011510694A JP5701750B2 JP 5701750 B2 JP5701750 B2 JP 5701750B2 JP 2011510694 A JP2011510694 A JP 2011510694A JP 2011510694 A JP2011510694 A JP 2011510694A JP 5701750 B2 JP5701750 B2 JP 5701750B2
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- pharmaceutically acceptable
- compound
- solvate
- acceptable salt
- foregoing
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Classifications
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- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/04—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C233/07—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
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- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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- 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
- A61K31/47—Quinolines; Isoquinolines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
Landscapes
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
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| JP5757864B2 (ja) * | 2008-05-20 | 2015-08-05 | ニューロジェシックス， インコーポレイテッド | 水溶性アセトアミノフェン類似体 |
| AU2009249071A1 (en) | 2008-05-20 | 2009-11-26 | Neurogesx, Inc. | Hepatoprotectant acetaminophen mutual prodrugs |
| AU2009249069A1 (en) | 2008-05-20 | 2009-11-26 | Neurogesx, Inc. | Carbonate prodrugs and methods of using the same |
| EP2758133A4 (en) | 2011-09-22 | 2015-05-27 | Acorda Therapeutics Inc | ACETAMINOPHONE CONJUGATES, COMPOSITIONS AND METHOD OF USE THEREOF |
| US20140179615A1 (en) * | 2012-07-12 | 2014-06-26 | Hainan Weikang Pharmaceutical (Qianshan) Co., Ltd. | Glutathione and Acetaminophen Composition and Preparation Method Thereof |
| CA3042642A1 (en) | 2013-08-12 | 2015-02-19 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded immediate release abuse deterrent pill |
| WO2015095391A1 (en) | 2013-12-17 | 2015-06-25 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
| US9492444B2 (en) | 2013-12-17 | 2016-11-15 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
| DK3169315T3 (da) | 2014-07-17 | 2020-08-10 | Pharmaceutical Manufacturing Res Services In | Væskefyldt doseringsform til forhindring af misbrug med øjeblikkelig frigivelse |
| WO2016025897A1 (en) * | 2014-08-15 | 2016-02-18 | Purdue Pharma L.P. | Acetaminophen-containing analgesic formulations with reduced hepatotoxicity |
| AU2015336065A1 (en) | 2014-10-20 | 2017-05-04 | Pharmaceutical Manufacturing Research Services, Inc. | Extended release abuse deterrent liquid fill dosage form |
| US11389409B2 (en) * | 2019-08-30 | 2022-07-19 | Remedy Diagnostics LLC | Transdermal device comprising acetaminophen prodrug |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4035507A (en) * | 1975-04-17 | 1977-07-12 | Interx Research Corporation | Novel, transient pro-drug forms of L-DOPA to treat Parkinson's disease |
| GB1583602A (en) | 1977-05-26 | 1981-01-28 | Sterwin Ag | N-acetyl-para-aminophenyl-n'-acetyl-amino-thioalkanoic acid ester derivatives |
| US4562024A (en) | 1982-07-06 | 1985-12-31 | Sterling Drug Inc. | Process for preparing granulate containing poorly compressible medicinally active matter |
| CH654302A5 (de) * | 1983-05-04 | 1986-02-14 | Sandoz Ag | Acylaminophenolderivate, ihre herstellung und arzneimittel, welche sie enthalten. |
| US5001115A (en) * | 1989-05-17 | 1991-03-19 | University Of Florida | Prodrugs of biologically active hydroxyaromatic compounds |
| US5474757A (en) * | 1992-10-16 | 1995-12-12 | Rutgers University | Prevention of acetaminophen overdose toxicity with organosulfur compounds |
| DE4327462A1 (de) * | 1993-08-16 | 1995-02-23 | Carl Heinrich Dr Weischer | Neue N-Acetyl-p-Aminophenol-Derivate zur Bekämpfung von Schmerzzuständen |
| US5916910A (en) | 1997-06-04 | 1999-06-29 | Medinox, Inc. | Conjugates of dithiocarbamates with pharmacologically active agents and uses therefore |
| US6710086B1 (en) | 2000-02-25 | 2004-03-23 | Medinox, Inc. | Protected forms of pharmacologically active agents and uses therefor |
| ES2234840T3 (es) | 2000-03-14 | 2005-07-01 | Actelion Pharmaceuticals Ltd. | Derivados de 1,2,3,4- tetrahidroisoquinolina. |
| WO2001068069A2 (en) | 2000-03-15 | 2001-09-20 | King's College London | Pharmaceutical composition comprising paracetamol |
| IT1319202B1 (it) | 2000-10-12 | 2003-09-26 | Nicox Sa | Farmaci per le malattie a base infiammatoria. |
| US20030073618A1 (en) * | 2001-02-08 | 2003-04-17 | Kozhemyakin Leonid A. | Compounds comprising disulfide-containing peptides and nitrogenous bases, and medical uses thereof |
| KR20030033007A (ko) | 2001-05-31 | 2003-04-26 | 코울터 파머수티컬, 인코포레이티드 | 세포독소, 약물전구체, 링커 및 이에 유용한 안정화제 |
| NZ529661A (en) | 2001-06-05 | 2006-03-31 | Control Delivery Systems | Sustained-release analgesic compounds |
| US20030118528A1 (en) | 2001-11-19 | 2003-06-26 | Walters Kenneth A. | Topical delivery of codrugs |
| US20050164994A1 (en) | 2001-12-10 | 2005-07-28 | Control Deliver Systems, Inc. | Treatment of genitourinary tract disorders |
| EP1461122A4 (en) | 2001-12-10 | 2006-08-23 | Control Delivery Sys Inc | TREATMENT OF DISEASES OF THE UROGENITAL SYSTEM |
| WO2003061626A1 (en) | 2002-01-18 | 2003-07-31 | Control Delivery Systems, Inc. | Polymeric gel system for the controlled delivery of codrugs |
| US20040058946A1 (en) | 2002-07-05 | 2004-03-25 | Buchwald Stephen L. | Abuse-resistant prodrugs of oxycodone and other pharmaceuticals |
| US7381721B2 (en) | 2003-03-17 | 2008-06-03 | Adolor Corporation | Substituted piperidine compounds |
| KR20140015122A (ko) | 2003-10-01 | 2014-02-06 | 아돌로 코포레이션 | 스피로시클릭 헤테로시클릭 유도체 및 이의 사용 방법 |
| CN100453528C (zh) | 2003-11-12 | 2009-01-21 | 应用超微系统股份有限公司 | 非对称胶凝剂 |
| US20050113294A1 (en) | 2003-11-21 | 2005-05-26 | Adolor Corporation. | Carboxamide and amino derivatives and methods of their use |
| TW200616604A (en) | 2004-08-26 | 2006-06-01 | Nicholas Piramal India Ltd | Nitric oxide releasing prodrugs containing bio-cleavable linker |
| US7598261B2 (en) | 2005-03-31 | 2009-10-06 | Adolor Corporation | Spirocyclic heterocyclic derivatives and methods of their use |
| JP2009502931A (ja) | 2005-07-27 | 2009-01-29 | オレキシジェン・セラピューティクス・インコーポレーテッド | 体重減少を促すための組成物 |
| EP1998781A2 (en) | 2006-03-24 | 2008-12-10 | Wyeth a Corporation of the State of Delaware | Treatment of pain |
| EP2121029A2 (en) | 2006-12-05 | 2009-11-25 | Neurogesx, Inc. | Prodrugs and methods of making and using the same |
| JP5757864B2 (ja) | 2008-05-20 | 2015-08-05 | ニューロジェシックス， インコーポレイテッド | 水溶性アセトアミノフェン類似体 |
| AU2009249071A1 (en) | 2008-05-20 | 2009-11-26 | Neurogesx, Inc. | Hepatoprotectant acetaminophen mutual prodrugs |
| AU2009249069A1 (en) | 2008-05-20 | 2009-11-26 | Neurogesx, Inc. | Carbonate prodrugs and methods of using the same |
-
2009
- 2009-05-20 AU AU2009249071A patent/AU2009249071A1/en not_active Abandoned
- 2009-05-20 JP JP2011510694A patent/JP5701750B2/ja not_active Expired - Fee Related
- 2009-05-20 RU RU2010151951/15A patent/RU2010151951A/ru not_active Application Discontinuation
- 2009-05-20 WO PCT/US2009/044749 patent/WO2009143299A1/en not_active Ceased
- 2009-05-20 KR KR1020107028511A patent/KR101717145B1/ko not_active Expired - Fee Related
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- 2009-05-20 CA CA2724788A patent/CA2724788C/en not_active Expired - Fee Related
- 2009-05-20 US US12/993,091 patent/US20110263545A1/en not_active Abandoned
- 2009-05-20 CN CN2009801282430A patent/CN102149412A/zh active Pending
- 2009-05-20 EP EP09751527A patent/EP2285419A4/en not_active Withdrawn
- 2009-05-20 BR BRPI0912820A patent/BRPI0912820A2/pt not_active IP Right Cessation
- 2009-05-20 MX MX2010012647A patent/MX2010012647A/es active IP Right Grant
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2010
- 2010-11-17 IL IL209384A patent/IL209384A0/en unknown
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2014
- 2014-02-03 JP JP2014018474A patent/JP2014111632A/ja not_active Withdrawn
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2015
- 2015-09-14 JP JP2015180278A patent/JP2015227384A/ja not_active Withdrawn
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2017
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2019
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Also Published As
| Publication number | Publication date |
|---|---|
| MX2010012647A (es) | 2010-12-14 |
| EP2285419A1 (en) | 2011-02-23 |
| CA2724788A1 (en) | 2009-11-26 |
| JP2019081793A (ja) | 2019-05-30 |
| US20190062273A1 (en) | 2019-02-28 |
| JP2011523645A (ja) | 2011-08-18 |
| CA2724788C (en) | 2016-12-06 |
| JP2014111632A (ja) | 2014-06-19 |
| JP2017186380A (ja) | 2017-10-12 |
| JP2015227384A (ja) | 2015-12-17 |
| US20110263545A1 (en) | 2011-10-27 |
| RU2010151951A (ru) | 2012-06-27 |
| US9951001B2 (en) | 2018-04-24 |
| WO2009143299A1 (en) | 2009-11-26 |
| AU2009249071A1 (en) | 2009-11-26 |
| BRPI0912820A2 (pt) | 2015-10-13 |
| KR101717145B1 (ko) | 2017-03-16 |
| US20160326107A1 (en) | 2016-11-10 |
| KR20110011694A (ko) | 2011-02-08 |
| JP2021036001A (ja) | 2021-03-04 |
| EP2285419A4 (en) | 2012-05-02 |
| IL209384A0 (en) | 2011-01-31 |
| CA2946445C (en) | 2019-01-08 |
| CA2946445A1 (en) | 2009-11-26 |
| CN102149412A (zh) | 2011-08-10 |
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