RU2612351C2 - Сложноэфирные пролекарства [3-(1-(1h-имидазол-4-ил)этил)-2-метилфенил]метанола - Google Patents
Сложноэфирные пролекарства [3-(1-(1h-имидазол-4-ил)этил)-2-метилфенил]метанола Download PDFInfo
- Publication number
- RU2612351C2 RU2612351C2 RU2013116541A RU2013116541A RU2612351C2 RU 2612351 C2 RU2612351 C2 RU 2612351C2 RU 2013116541 A RU2013116541 A RU 2013116541A RU 2013116541 A RU2013116541 A RU 2013116541A RU 2612351 C2 RU2612351 C2 RU 2612351C2
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- RU
- Russia
- Prior art keywords
- methyl
- ethyl
- imidazol
- acid
- benzyl ether
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- -1 iso-butyric acid 3 - [(S) -1- (1H-imidazol-4-yl) ethyl] -2-methyl-benzyl ester Chemical class 0.000 claims description 34
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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| PCT/US2011/052004 WO2012037499A1 (en) | 2010-09-16 | 2011-09-16 | Ester pro-drugs of [3-(1-(1h-imidazol-4-yl)ethyl)-2-methylphenyl] methanol |
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| RU2013116403/15A RU2013116403A (ru) | 2010-09-16 | 2011-09-16 | Сложноэфирные пролекарства [3-(1-(1h-имидазол-4-ил)этил)-2-метилфенил]метанола для лечения заболеваний сетчатки |
| RU2013116405/15A RU2013116405A (ru) | 2010-09-16 | 2011-09-16 | Сложноэфирные пролекарства [3-(1-(1н-имидазол-4-ил)этил)-2-метилфенил]метанола для лечения заболеваний и состояний кожи |
| RU2013116763/15A RU2013116763A (ru) | 2010-09-16 | 2011-09-16 | Сложноэфирные пролекарства [3-(1-(1н-имидазол-4)этил)-2-метилфенил]метанола для снижения внутриглазного давления |
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| RU2013116405/15A RU2013116405A (ru) | 2010-09-16 | 2011-09-16 | Сложноэфирные пролекарства [3-(1-(1н-имидазол-4-ил)этил)-2-метилфенил]метанола для лечения заболеваний и состояний кожи |
| RU2013116763/15A RU2013116763A (ru) | 2010-09-16 | 2011-09-16 | Сложноэфирные пролекарства [3-(1-(1н-имидазол-4)этил)-2-метилфенил]метанола для снижения внутриглазного давления |
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| JP2012518007A (ja) | 2009-02-13 | 2012-08-09 | アラーガン インコーポレイテッド | （３‐（１‐（１ｈ‐イミダゾール‐４‐イル）エチル）‐２‐メチルフェニル）メタノールを含む医薬組成物 |
| KR101841442B1 (ko) | 2010-01-11 | 2018-03-23 | 오렉시젠 세러퓨틱스 인크. | 주우울증 환자들에 있어서 체중 감량 치료를 제공하는 방법 |
| US8653123B2 (en) * | 2010-09-16 | 2014-02-18 | Allergan, Inc. | Ester pro-drugs of [3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl] methanol for treating retinal diseases |
| WO2013016073A1 (en) * | 2011-07-22 | 2013-01-31 | Allergan, Inc. | Alpha-2 adrenergic modulators for treating visual disorders mediated by central visual projections from the eye |
| EP2782569A1 (en) | 2011-11-21 | 2014-10-01 | Allergan, Inc. | Pharmaceutical compositions comprising 4-[1-(2,3-dimethylphenyl)ethyl]-3h-imidazole derivatives for treating retinal diseases |
| USD794650S1 (en) | 2014-11-28 | 2017-08-15 | Samsung Electronics Co., Ltd. | Display screen or portion thereof with a graphical user interface |
| CN108310442B (zh) * | 2017-01-17 | 2021-08-27 | 台北科技大学 | 眼科用组合物 |
| KR102050506B1 (ko) | 2017-06-20 | 2019-11-29 | 한국식품연구원 | 망막 질환 예방, 개선, 완화 또는 치료용 조성물 |
| CN108872431B (zh) * | 2018-07-09 | 2021-03-23 | 成都倍特药业股份有限公司 | 一种检测4-(1-(2,5-二甲基苯基)乙基)-1h-咪唑或/和其盐酸盐的方法 |
| CN112552314B (zh) * | 2018-08-24 | 2022-03-04 | 杭州阿诺生物医药科技有限公司 | Sting激动剂小分子抗肿瘤化合物及其应用 |
| AU2022258105A1 (en) * | 2021-04-16 | 2023-10-26 | Ads Therapeutics Llc | Alpha2 adrenergic agonist codrugs conjugated with muscarinic agonist drugs |
| KR20250141793A (ko) * | 2023-02-08 | 2025-09-29 | 보슈 롬 아일랜드 리미티드 | 시력을 개선시키기 위한 알파-2-아드레날린성 효능제 |
| WO2025179071A1 (en) * | 2024-02-20 | 2025-08-28 | Bausch + Lomb Ireland Limited | Sustained-release drug delivery compositions for treating ocular diseases |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995014007A1 (en) * | 1993-11-15 | 1995-05-26 | Schering Corporation | Phenyl-alkyl imidazoles as h3-receptor antagonists |
| EA200501870A1 (ru) * | 2003-05-27 | 2006-06-30 | Сосьете Де Консей Решерш Э Д`Аппликасьон Сьентифик (С.К.Р.А.С.) | Новые производные имидазолов, способ их получения и их применение в качестве лекарственного средства |
| WO2010093930A1 (en) * | 2009-02-13 | 2010-08-19 | Allergan, Inc. | Pharmaceutical compositions comprising (3-(1-(1h-imidazol-4-yl)ethyl)-2-methylphenyl)methanol |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0642332T3 (da) | 1992-05-13 | 1997-06-16 | Sandoz Ltd | Ophthalmiske præparater indeholdende cyclosporin |
| US5459133A (en) * | 1992-06-05 | 1995-10-17 | Telor Ophthalmic Pharmaceuticals, Inc. | Methods and products for treating presbyopia |
| US5474979A (en) | 1994-05-17 | 1995-12-12 | Allergan, Inc. | Nonirritating emulsions for sensitive tissue |
| EP0957073A1 (en) * | 1998-05-12 | 1999-11-17 | Schwarz Pharma Ag | Novel derivatives of 3,3-diphenylpropylamines |
| US20040214829A1 (en) * | 2000-07-14 | 2004-10-28 | Allergan, Inc. | Compositions containing alpha-2-adrenergic agonist components |
| US20020198209A1 (en) | 2001-05-03 | 2002-12-26 | Allergan Sales Inc. | Compositions having enhanced pharmacokinetic characteristics |
| US7439241B2 (en) * | 2003-05-27 | 2008-10-21 | Galderma Laboratories, Inc. | Compounds, formulations, and methods for treating or preventing rosacea |
| CN1823518A (zh) * | 2003-07-14 | 2006-08-23 | 皇家飞利浦电子股份有限公司 | 投影设备 |
| CA2538445A1 (en) | 2003-09-12 | 2005-04-21 | Allergan, Inc. | Methods and compositions for the treatment of pain and other alpha 2 adrenergic-mediated conditions |
| US20050059583A1 (en) | 2003-09-15 | 2005-03-17 | Allergan, Inc. | Methods of providing therapeutic effects using cyclosporin components |
| US20050244463A1 (en) * | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Sustained release intraocular implants and methods for treating ocular vasculopathies |
| MXPA06013649A (es) | 2004-05-25 | 2007-07-09 | Sansrosa Pharmaceutical Dev In | Compuestos, formulaciones, y metodos para tratar o prevenir desordenes inflamatorios de la piel. |
| US20050277584A1 (en) | 2004-06-09 | 2005-12-15 | Allergan, Inc. | Pharmaceutical compositions comprising cyclosporins |
| CN101031549A (zh) * | 2004-09-24 | 2007-09-05 | 阿勒根公司 | 作为特异性α2肾上腺素能激动剂的4－（苯甲基和取代苯甲基）－咪唑－2－硫酮 |
| US7931909B2 (en) | 2005-05-10 | 2011-04-26 | Allergan, Inc. | Ocular therapy using alpha-2 adrenergic receptor compounds having enhanced anterior clearance rates |
| US7297679B2 (en) | 2005-07-13 | 2007-11-20 | Allergan, Inc. | Cyclosporin compositions |
| US20070015691A1 (en) | 2005-07-13 | 2007-01-18 | Allergan, Inc. | Cyclosporin compositions |
| US20070082070A1 (en) * | 2005-10-11 | 2007-04-12 | Stookey Evangeline L | Treating skin disorders |
| US7902247B2 (en) | 2008-01-09 | 2011-03-08 | Allergan, Inc. | Substituted-aryl-2-phenylethyl-1H-imidazole compounds as subtype selective modulators of alpha 2B and/or alpha 2C adrenergic receptors |
| AU2010210513A1 (en) | 2009-02-06 | 2011-09-01 | Allergan, Inc. | Pyridine compounds as subtype selective modulators of alpha2B and/or alpha 2C adrenergic receptors |
| US8394800B2 (en) * | 2009-11-19 | 2013-03-12 | Galderma Laboratories, L.P. | Method for treating psoriasis |
| US8653123B2 (en) * | 2010-09-16 | 2014-02-18 | Allergan, Inc. | Ester pro-drugs of [3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl] methanol for treating retinal diseases |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995014007A1 (en) * | 1993-11-15 | 1995-05-26 | Schering Corporation | Phenyl-alkyl imidazoles as h3-receptor antagonists |
| EA200501870A1 (ru) * | 2003-05-27 | 2006-06-30 | Сосьете Де Консей Решерш Э Д`Аппликасьон Сьентифик (С.К.Р.А.С.) | Новые производные имидазолов, способ их получения и их применение в качестве лекарственного средства |
| WO2010093930A1 (en) * | 2009-02-13 | 2010-08-19 | Allergan, Inc. | Pharmaceutical compositions comprising (3-(1-(1h-imidazol-4-yl)ethyl)-2-methylphenyl)methanol |
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