ES2325782T3 - Empleo de compuestos efectivos como moduladores selectivos de receptores de opiaceos. - Google Patents
Empleo de compuestos efectivos como moduladores selectivos de receptores de opiaceos. Download PDFInfo
- Publication number
- ES2325782T3 ES2325782T3 ES03752716T ES03752716T ES2325782T3 ES 2325782 T3 ES2325782 T3 ES 2325782T3 ES 03752716 T ES03752716 T ES 03752716T ES 03752716 T ES03752716 T ES 03752716T ES 2325782 T3 ES2325782 T3 ES 2325782T3
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- Prior art keywords
- effective
- asimadoline
- compounds
- receptor
- selective
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02011047 | 2002-05-17 | ||
| EP02011047 | 2002-05-17 |
Publications (1)
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| ES2325782T3 true ES2325782T3 (es) | 2009-09-17 |
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| EP (2) | EP2074997A1 (enExample) |
| JP (1) | JP2005531557A (enExample) |
| KR (1) | KR101108014B1 (enExample) |
| CN (2) | CN101310723A (enExample) |
| AR (1) | AR040028A1 (enExample) |
| AT (1) | ATE429226T1 (enExample) |
| AU (1) | AU2003242527B2 (enExample) |
| BR (1) | BR0309969A (enExample) |
| CA (1) | CA2486000A1 (enExample) |
| DE (1) | DE60327315D1 (enExample) |
| DK (1) | DK1505974T3 (enExample) |
| ES (1) | ES2325782T3 (enExample) |
| MX (1) | MXPA04011333A (enExample) |
| PE (1) | PE20040455A1 (enExample) |
| PL (1) | PL371596A1 (enExample) |
| RU (1) | RU2336871C2 (enExample) |
| TW (1) | TWI314053B (enExample) |
| WO (1) | WO2003097051A2 (enExample) |
| ZA (1) | ZA200410160B (enExample) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10259245A1 (de) * | 2002-12-17 | 2004-07-01 | Merck Patent Gmbh | Derivate des Asimadolins mit kovalent gebundenen Säuren |
| DE602004007105T2 (de) | 2003-01-28 | 2008-02-28 | Microbia Inc., Cambridge | Zusammensetzung zur behandlung von gastrointestinalen störungen |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| PT2316456T (pt) | 2003-04-29 | 2017-09-05 | Orexigen Therapeutics Inc | Composições para afetar a perda de peso compreendendo naltrexona e bupropion |
| EP1870096A3 (en) * | 2003-04-29 | 2011-04-20 | Orexigen Therapeutics, Inc. | Compositions for affecting weight loss |
| US20080090859A1 (en) * | 2003-10-30 | 2008-04-17 | Tioga Pharmaceuticals, Inc. | Use of Selective Opiate Receptor Modulators In the Treatment Of Neuropathy |
| CN101370488B (zh) | 2005-11-22 | 2012-07-18 | 奥雷西根治疗公司 | 增加胰岛素敏感性的组合物 |
| US8916195B2 (en) | 2006-06-05 | 2014-12-23 | Orexigen Therapeutics, Inc. | Sustained release formulation of naltrexone |
| US20080110792A1 (en) | 2006-11-09 | 2008-05-15 | Orexigen Therapeutics, Inc. | Methods for administering weight loss medications |
| CA2682608A1 (en) * | 2007-03-30 | 2008-10-09 | Tioga Pharmaceuticals, Inc. | Kappa-opiate agonists for the treatment of diarrhea-predominant and alternating irritable bowel syndrome |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| ES2393885T7 (es) | 2007-06-04 | 2014-01-30 | Synergy Pharmaceuticals Inc. | Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
| MX2010012909A (es) | 2008-05-30 | 2011-02-25 | Orexigen Therapeutics Inc | Metodos para tratamiento de condiciones de grasa visceral. |
| WO2009149279A2 (en) | 2008-06-04 | 2009-12-10 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| AU2009270833B2 (en) | 2008-07-16 | 2015-02-19 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| WO2010065751A2 (en) | 2008-12-03 | 2010-06-10 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase c agonists and methods of use |
| EP3351248B1 (en) | 2008-12-31 | 2021-06-09 | Ardelyx, Inc. | Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| WO2018129556A1 (en) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| RU2413512C1 (ru) * | 2009-07-29 | 2011-03-10 | Федеральное государственное автономное образовательное учреждение высшего профессионального образования "ЮЖНЫЙ ФЕДЕРАЛЬНЫЙ УНИВЕРСИТЕТ" | Средство, обладающее каппа-опиоидной агонистической активностью |
| KR101841442B1 (ko) | 2010-01-11 | 2018-03-23 | 오렉시젠 세러퓨틱스 인크. | 주우울증 환자들에 있어서 체중 감량 치료를 제공하는 방법 |
| US9303027B2 (en) | 2010-07-19 | 2016-04-05 | Dr. Reddy's Laboratories Ltd. | Kappa opioid receptor agonists |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| EP3366698A1 (en) | 2011-03-01 | 2018-08-29 | Synergy Pharmaceuticals Inc. | Guanylate cyclase c agonists |
| IL300868A (en) | 2012-06-06 | 2023-04-01 | Orexigen Therapeutics Inc | Methods for treating overweight and obesity |
| US10376481B2 (en) | 2012-08-21 | 2019-08-13 | Ardelyx, Inc. | Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| CA2880338A1 (en) | 2012-08-21 | 2014-02-27 | Ardelyx, Inc. | Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| US9675587B2 (en) | 2013-03-14 | 2017-06-13 | Allergan Holdings Unlimited Company | Opioid receptor modulator dosage formulations |
| WO2014151206A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| US9486494B2 (en) | 2013-03-15 | 2016-11-08 | Synergy Pharmaceuticals, Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| KR102287207B1 (ko) | 2013-04-12 | 2021-08-09 | 알데릭스, 인코포레이티드 | Nhe3-결합 화합물 및 포스페이트 수송을 저해하는 방법 |
| EP3004138B1 (en) | 2013-06-05 | 2024-03-13 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
| EA023231B1 (ru) * | 2013-07-18 | 2016-05-31 | Федеральное государственное бюджетное учреждение "Научно-исследовательский институт нормальной физиологии имени П.К. Анохина" Российской академии медицинских наук (ФГБУ "НИИНФ им. П.К. Анохина" РАМН) | Применение агониста каппа опиоидных рецепторов периферического действия ici 204,448 для приготовления средств для лечения синдрома отмены никотина |
| WO2015065867A2 (en) * | 2013-10-28 | 2015-05-07 | Cara Therapeutics, Inc. | Peripheral kappa opioid receptor agonists for preventing, inhibiting or treating nausea and vomiting |
| US8969371B1 (en) | 2013-12-06 | 2015-03-03 | Orexigen Therapeutics, Inc. | Compositions and methods for weight loss in at risk patient populations |
| JP2020505333A (ja) | 2017-01-09 | 2020-02-20 | アルデリックス， インコーポレイテッド | Ｎｈｅ媒介性アンチポートの阻害薬 |
| CN110267944B (zh) | 2017-01-09 | 2024-03-08 | 阿德利克斯股份有限公司 | 可用于治疗胃肠道病症的化合物 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4889860A (en) * | 1985-09-23 | 1989-12-26 | Nova Pharmaceutical Corporation | Oximes of oxymorphone, naltrexone and naloxone as potent, selective opioid receptor agonists and antagonists |
| DE3935371A1 (de) | 1988-12-23 | 1990-07-05 | Merck Patent Gmbh | Stickstoffhaltige ringverbindungen |
| DE4034785A1 (de) | 1990-11-02 | 1992-05-07 | Merck Patent Gmbh | 1-(2-arylethyl)-pyrrolidine |
| US5389686A (en) * | 1989-02-20 | 1995-02-14 | Jouveinal Sa | Analgesic properties of fedotozine |
| DE4215213A1 (de) | 1992-05-09 | 1993-11-11 | Merck Patent Gmbh | Arylacetamide |
| DE4215231C1 (en) | 1992-05-09 | 1993-05-13 | Dornier Luftfahrt Gmbh, 8031 Wessling, De | Arrangement for mfg. fibre reinforced thermoplastic components - including unit for accommodating component, pressurising unit for assembled component and heating unit |
| DE19523502A1 (de) * | 1995-06-28 | 1997-01-02 | Merck Patent Gmbh | Kappa-Opiatagonisten für entzündliche Darmerkrankungen |
| DE19531464A1 (de) * | 1995-08-26 | 1997-02-27 | Merck Patent Gmbh | N-Methyl-N-[(1S-)-1-phenyl-2-((3S)-3-hydroxypyrrolidin 1-yl-)-ethyl]-2,2-diphenyl-acetamid |
| ES2252865T3 (es) * | 1997-09-26 | 2006-05-16 | Noven Pharmaceuticals, Inc. | Composiciones bioadhesivas y metodos para la administracion topica de agentes activos. |
| US20010051181A1 (en) * | 1997-12-22 | 2001-12-13 | Van Osdol William W. | Novel formulations for the transdermal administration of asimadoline |
| JPH11343244A (ja) * | 1998-03-30 | 1999-12-14 | Taisho Pharmaceut Co Ltd | 経口用組成物 |
| JP2000080047A (ja) * | 1998-06-30 | 2000-03-21 | Takeda Chem Ind Ltd | 医 薬 |
| WO2000004050A2 (en) * | 1998-07-14 | 2000-01-27 | Janssen Pharmaceutica N.V. | Neurotrophic growth factor |
| DE60018225T2 (de) * | 1999-03-01 | 2005-12-29 | Pfizer Products Inc., Groton | Oxamsäuren mit einer Cyanogruppe als Liganden für den Thyroidrezeptor |
| JP2005508830A (ja) * | 2000-06-19 | 2005-04-07 | エーザイ株式会社 | ピリジン誘導体を用いる方法 |
| DE10030893A1 (de) * | 2000-06-23 | 2002-01-03 | Henkel Kgaa | Paraaminophenol-Derivate und deren Verwendung |
| GB0015562D0 (en) * | 2000-06-23 | 2000-08-16 | Pfizer Ltd | Heterocycles |
| US6262062B1 (en) * | 2000-08-15 | 2001-07-17 | Cpd, Llc | Method of treating the syndrome of coronary heart disease risk factors in humans |
| US6569449B1 (en) * | 2000-11-13 | 2003-05-27 | University Of Kentucky Research Foundation | Transdermal delivery of opioid antagonist prodrugs |
| US6780891B2 (en) * | 2001-11-30 | 2004-08-24 | Sepracor Inc. | Tramadol analogs and uses thereof |
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2003
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- 2003-04-28 CA CA002486000A patent/CA2486000A1/en not_active Abandoned
- 2003-04-28 MX MXPA04011333A patent/MXPA04011333A/es active IP Right Grant
- 2003-04-28 US US10/514,887 patent/US20050176746A1/en not_active Abandoned
- 2003-04-28 WO PCT/EP2003/004428 patent/WO2003097051A2/en not_active Ceased
- 2003-04-28 CN CNA2008101295692A patent/CN101310723A/zh active Pending
- 2003-04-28 BR BR0309969-5A patent/BR0309969A/pt not_active Application Discontinuation
- 2003-04-28 DK DK03752716T patent/DK1505974T3/da active
- 2003-04-28 AT AT03752716T patent/ATE429226T1/de not_active IP Right Cessation
- 2003-04-28 DE DE60327315T patent/DE60327315D1/de not_active Expired - Lifetime
- 2003-04-28 EP EP03752716A patent/EP1505974B1/en not_active Expired - Lifetime
- 2003-04-28 CN CNB038111373A patent/CN100411618C/zh not_active Expired - Fee Related
- 2003-04-28 KR KR1020047018468A patent/KR101108014B1/ko not_active Expired - Fee Related
- 2003-04-28 RU RU2004137091/15A patent/RU2336871C2/ru not_active IP Right Cessation
- 2003-04-28 PL PL03371596A patent/PL371596A1/xx not_active Application Discontinuation
- 2003-04-28 ES ES03752716T patent/ES2325782T3/es not_active Expired - Lifetime
- 2003-04-28 AU AU2003242527A patent/AU2003242527B2/en not_active Ceased
- 2003-04-28 JP JP2004505050A patent/JP2005531557A/ja active Pending
- 2003-05-12 TW TW092112843A patent/TWI314053B/zh not_active IP Right Cessation
- 2003-05-13 PE PE2003000457A patent/PE20040455A1/es not_active Application Discontinuation
- 2003-05-16 AR ARP030101709A patent/AR040028A1/es unknown
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2004
- 2004-12-15 ZA ZA2004/10160A patent/ZA200410160B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RU2336871C2 (ru) | 2008-10-27 |
| EP2074997A1 (en) | 2009-07-01 |
| KR101108014B1 (ko) | 2012-01-25 |
| AU2003242527A1 (en) | 2003-12-02 |
| US20050176746A1 (en) | 2005-08-11 |
| AU2003242527B2 (en) | 2008-10-23 |
| MXPA04011333A (es) | 2005-02-14 |
| CN101310723A (zh) | 2008-11-26 |
| ATE429226T1 (de) | 2009-05-15 |
| CN100411618C (zh) | 2008-08-20 |
| HK1079451A1 (zh) | 2006-04-07 |
| RU2004137091A (ru) | 2005-09-10 |
| CA2486000A1 (en) | 2003-11-27 |
| WO2003097051A2 (en) | 2003-11-27 |
| EP1505974B1 (en) | 2009-04-22 |
| CN1655784A (zh) | 2005-08-17 |
| TWI314053B (en) | 2009-09-01 |
| ZA200410160B (en) | 2005-12-28 |
| DK1505974T3 (da) | 2009-08-17 |
| KR20050010807A (ko) | 2005-01-28 |
| DE60327315D1 (de) | 2009-06-04 |
| BR0309969A (pt) | 2005-04-26 |
| TW200307541A (en) | 2003-12-16 |
| PE20040455A1 (es) | 2004-08-07 |
| PL371596A1 (en) | 2005-06-27 |
| JP2005531557A (ja) | 2005-10-20 |
| EP1505974A2 (en) | 2005-02-16 |
| AR040028A1 (es) | 2005-03-09 |
| WO2003097051A3 (en) | 2004-12-09 |
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