AU2005257997B2 - Retinal derivatives and methods for the use thereof for the treatment of visual disorders - Google Patents
Retinal derivatives and methods for the use thereof for the treatment of visual disorders Download PDFInfo
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- AU2005257997B2 AU2005257997B2 AU2005257997A AU2005257997A AU2005257997B2 AU 2005257997 B2 AU2005257997 B2 AU 2005257997B2 AU 2005257997 A AU2005257997 A AU 2005257997A AU 2005257997 A AU2005257997 A AU 2005257997A AU 2005257997 B2 AU2005257997 B2 AU 2005257997B2
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- Prior art keywords
- cis
- retinyl
- ester
- retinal derivative
- retinal
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- C07C403/10—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms by etherified hydroxy groups
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- C07C403/06—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms
- C07C403/12—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms by esterified hydroxy groups
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- C07C403/14—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by doubly-bound oxygen atoms
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/20—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by carboxyl groups or halides, anhydrides, or (thio)esters thereof
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/52—Esters of acyclic unsaturated carboxylic acids having the esterified carboxyl group bound to an acyclic carbon atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
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Landscapes
- Health & Medical Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Physiology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (2)
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| AU2012216808A AU2012216808B2 (en) | 2004-06-18 | 2012-09-12 | Retinal derivatives and methods for the use thereof for the treatment of visual disorders |
| AU2015207903A AU2015207903B2 (en) | 2004-06-18 | 2015-07-30 | Retinal derivatives and methods for the use thereof for the treatment of visual disorders |
Applications Claiming Priority (3)
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| US58088904P | 2004-06-18 | 2004-06-18 | |
| US60/580,889 | 2004-06-18 | ||
| PCT/US2005/021812 WO2006002097A2 (en) | 2004-06-18 | 2005-06-20 | Retinal derivatives and methods for the use thereof for the treatment of visual disorders |
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| AU2012216808A Division AU2012216808B2 (en) | 2004-06-18 | 2012-09-12 | Retinal derivatives and methods for the use thereof for the treatment of visual disorders |
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| AU2005257997A1 AU2005257997A1 (en) | 2006-01-05 |
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| US20040242704A1 (en) | 2003-03-14 | 2004-12-02 | University Of Washington, Techtransfer - Invention Licensing | Stabilized mutant opsin proteins |
| BRPI0511396B1 (pt) | 2004-06-18 | 2021-07-27 | University Of Washington | Uso de 9-cis-retinil éster e uso de um derivado de retinal sintético |
| SI1768657T1 (sl) | 2004-06-23 | 2009-02-28 | Sirion Terapeutics Inc | Postopki in sestavki za zdravljenje oftalmičnih obolenj z derivati retinila |
| CA2638753A1 (en) * | 2004-12-08 | 2006-06-15 | Sirion Therapeutics, Inc. | Methods, assays and compositions for treating retinol-related diseases |
| EP2069390A4 (en) * | 2006-07-27 | 2009-12-30 | Univ Florida | OPSIN STABILIZING COMPOUNDS AND METHODS OF USE |
| CA2657238A1 (en) * | 2006-07-27 | 2008-01-31 | University Of Florida Research Foundation, Inc. | Compositions and methods for treating or preventing ophthalmic disease |
| WO2008063768A2 (en) * | 2006-10-12 | 2008-05-29 | Case Western Reserve University | Compositions and methods for treating metabolic diseases |
| BRPI0810063A2 (pt) | 2007-04-20 | 2014-10-14 | Acucela Inc | Composto, composição farmacêutica, e, métodos para modular fluxo de cromóforo em um ciclo retinóide, para tratar uma doença ou distúrbio oftálmico em um indivíduo, para inibir adaptação ao escuro em uma célula fotorreceptora de bastão da retina, para inibir regeneração de rodopsina em uma célula fotoreceptora de bastão da retina, para reduzir isquemia em um olho de um indivíduo, para inibir neovascularização na retina de um olho de um indivíduo, e para inibir degeneração de uma célula da retina em uma retina |
| JP6022746B2 (ja) * | 2008-02-11 | 2016-11-09 | ユニヴァーシティ オブ ワシントン | 加齢関連性網膜機能不全の治療及び予防方法 |
| AU2015200520B2 (en) * | 2008-02-11 | 2017-02-09 | University Of Washington | Methods for the treatment and prevention of age-related retinal dysfunction |
| JP5443470B2 (ja) * | 2008-04-29 | 2014-03-19 | 株式会社日健総本社 | 眼障害の治療方法 |
| IN2012DN00352A (https=) | 2009-06-16 | 2015-08-21 | Bikam Pharmaceuticals Inc | |
| RU2546005C2 (ru) * | 2009-09-15 | 2015-04-10 | Кью Эл Ти ИНК. | Фармацевтические составы, содержащие 9-цис-ретиниловые сложные эфиры в липидном наполнителе |
| EP2509596B1 (en) | 2009-12-08 | 2019-08-28 | Case Western Reserve University | Gamma aminoacids for treating ocular disorders |
| US8889660B2 (en) | 2010-01-20 | 2014-11-18 | Case Western Reserve University | Methods for treating obesity or an obesity related condition |
| US9173856B2 (en) | 2010-04-19 | 2015-11-03 | Qlt Inc. | Therapeutic regimen and methods for treating or ameliorating visual disorders associated with an endogenous retinoid deficiency |
| CN106106368A (zh) * | 2010-11-05 | 2016-11-16 | 斯坦福大学托管董事会 | 光控cns功能障碍 |
| WO2013082149A1 (en) * | 2011-11-28 | 2013-06-06 | Case Western Reserve University | Polysaccharide therapeutic conjugates |
| CA2865935C (en) * | 2012-03-01 | 2021-12-14 | Qlt Inc. | Therapeutic regimens and methods for improving visual function in visual disorders associated with an endogenous retinoid deficiency |
| US20150038582A1 (en) * | 2012-03-01 | 2015-02-05 | Qlt Inc. | Therapeutic regimens and methods for improving visual function in visual disorders associated with an endogenous retinoid deficiency |
| US9730941B2 (en) | 2012-06-07 | 2017-08-15 | Beth Israel Deaconess Medical Center, Inc. | Methods and compositions for the inhibition of Pin1 |
| WO2013188727A2 (en) * | 2012-06-15 | 2013-12-19 | The Children's Hospital Of Philadelphia | Novel pro- and codrug derivatives for nanoparticle delivery of select anticancer agents formed using rapidly cleavable phenolic ester bridges |
| US10471118B2 (en) | 2014-05-30 | 2019-11-12 | Case Western Reserve University | Retinylamine derivitives for treatment of ocular disorders |
| US11129845B2 (en) | 2014-06-18 | 2021-09-28 | Case Western Reserve University | Compositions and methods for the delivery of nucleic acids |
| WO2016011265A2 (en) | 2014-07-17 | 2016-01-21 | Beth Israel Deaconess Medical Center, Inc. | Biomarkers for pin1-associated disorders |
| US10925980B2 (en) | 2014-08-04 | 2021-02-23 | Case Western Reserve University | Molecular probes and methods of use |
| US10548864B2 (en) | 2015-03-12 | 2020-02-04 | Beth Israel Deaconess Medical Center, Inc. | Enhanced ATRA-related compounds for the treatment of proliferative diseases, autoimmune diseases, and addiction conditions |
| US11407786B2 (en) | 2015-06-18 | 2022-08-09 | Case Western Reserve University | Compositions and methods for the delivery of nucleic acids |
| US12060318B2 (en) | 2015-10-09 | 2024-08-13 | Case Western Reserve University | Compositions and methods for the delivery of nucleic acids |
| AU2017258776B2 (en) * | 2016-04-28 | 2023-07-13 | Spark Therapeutics, Inc. | Relative potency assay for viral vector encoding isomerohydrolases |
| EP4161502A4 (en) * | 2020-06-09 | 2024-07-10 | Eluminex Biosciences (Suzhou) Limited | Methods of treating visual disorders using daily low dosing of a retinoid compound |
| WO2023150258A1 (en) * | 2022-02-04 | 2023-08-10 | New York University | Use of retinoids for treatment of atrial fibrillation |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3196078A (en) * | 1962-01-30 | 1965-07-20 | Ortho Pharma Corp | Process for combating retinits pigmentosa |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB797977A (en) * | 1956-01-16 | 1958-07-09 | Hoffmann La Roche | Vitamin-a esters and a process for the manufacture thereof |
| US3196048A (en) | 1961-12-19 | 1965-07-20 | Exxon Research Engineering Co | Cathode catalyst for fuel cells |
| US3517067A (en) | 1964-02-11 | 1970-06-23 | Eastman Kodak Co | Syntheses of quaternary phosphonium salts |
| DE2300107C2 (de) * | 1973-01-03 | 1982-03-11 | Basf Ag, 6700 Ludwigshafen | Vitamin A-Säureanilid-4-carbonsäureäthylester, Verfahren zu seiner Herstellung und diesen enthaltende Zubereitungen |
| DE2456959A1 (de) * | 1974-12-03 | 1976-06-16 | Basf Ag | 4-(e)- und 4-(z)-7-methyl-9-(2,6,6trimethyl-1-cyclohexen-1-yl)-nona-2,4,6,8tetraencarbonsaeure, ihre derivate und diese enthaltende zubereitungen |
| JPS61275266A (ja) | 1985-05-28 | 1986-12-05 | Taisho Pharmaceut Co Ltd | レチノイド誘導体 |
| US5310764A (en) | 1992-05-08 | 1994-05-10 | Steven Baranowitz | Treatment of age related macular degeneration with beta-carotene |
| JPH06340525A (ja) * | 1993-06-02 | 1994-12-13 | Lion Corp | 安定な低眼刺激性ビタミンa類可溶化点眼剤 |
| WO1995026734A1 (en) | 1994-04-04 | 1995-10-12 | Freeman William R | Use of phosphonylmethoxyalkyl nucleosides for the treatment of raised intraocular pressure |
| RU2106843C1 (ru) * | 1994-06-29 | 1998-03-20 | Красноярская государственная медицинская академия | Способ лечения близорукости |
| JPH08198746A (ja) * | 1995-01-18 | 1996-08-06 | Lion Corp | 可溶化点眼剤 |
| US5837728A (en) | 1995-01-27 | 1998-11-17 | Molecular Design International | 9-cis retinoic acid esters and amides and uses thereof |
| US5489611A (en) | 1995-02-10 | 1996-02-06 | Warner-Lambert Company | Method for lowering plasma levels of lipoprotein (a) |
| CZ311997A3 (cs) * | 1995-04-03 | 1998-01-14 | Johnson & Johnson Consumer Products, Inc. | Kompozice určená k péči o pleť obsahující retinoidy a liposomy |
| US5620970A (en) * | 1995-06-05 | 1997-04-15 | Alcon Laboratories, Inc. | Topical ophthalmic carbonic anhydrase inhibitor formulations |
| US5716627A (en) | 1996-04-25 | 1998-02-10 | Elizabeth Arden Co., Division Of Conopco, Inc. | Skin care compositions containing fatty acid amides, azoles, and retinol or retinyl ester |
| EP0908179A1 (en) * | 1997-08-23 | 1999-04-14 | Werner Bollag | Treatment of cell-mediated immune diseases |
| US6391924B1 (en) | 1997-12-10 | 2002-05-21 | Hampar Karageozian | Taurine derivatives useable in the treatment of ophthalmic disorders |
| US6552009B2 (en) | 1998-07-16 | 2003-04-22 | Gentrix Llc | Compositions and methods of treating abnormal cell proliferation |
| US6372463B1 (en) | 1999-05-06 | 2002-04-16 | The President & Fellows Of Harvard College | Mutations in nucleic acid molecules encoding 11-CIS retinol dehydrogenase, the mutated proteins, and uses thereof |
| US6300328B1 (en) | 1999-08-06 | 2001-10-09 | Alcon Universal Ltd. | Selective inhibitors of adenosine monophosphate deaminase for the treatment of optic nerve and retinal damage |
| JP2003529567A (ja) | 2000-03-10 | 2003-10-07 | インサイト・ビジョン・インコーポレイテッド | 後眼部眼疾患を治療および予防する方法と組成物 |
| US20020028849A1 (en) | 2000-04-18 | 2002-03-07 | Godkin James D. | Use of retinol in assisted-reproduction protocols |
| US6696069B2 (en) | 2000-06-30 | 2004-02-24 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Skin care cosmetic compositions containing phosphates and/or sulfates of branched alcohols and/or ethoxylates thereof |
| JP4210115B2 (ja) * | 2001-01-11 | 2009-01-14 | チェビジェン・インコーポレイテッド | 新規レチノール誘導体および製造方法および用途 |
| WO2002058586A2 (en) | 2001-01-26 | 2002-08-01 | Steven Baranowitz | Systemic formulations containing beta-carotene and derivatives thereof |
| GB0103998D0 (en) | 2001-02-19 | 2001-04-04 | King S College London | Method |
| CA2442670A1 (en) | 2001-04-13 | 2002-10-24 | The Trustees Of The University Of Pennsylvania | Method of treating or retarding the development of blindness |
| CA2474154A1 (en) * | 2002-01-18 | 2003-07-24 | Tatton Technologies, Llc. | Methods for treating eye disorders |
| US20030215413A1 (en) | 2002-03-22 | 2003-11-20 | L'oreal | Compositions containing stabilized retinoid |
| US20040097587A1 (en) | 2002-03-27 | 2004-05-20 | Arbiser Jack L | Compositions and methods of treatment of ulcerating diseases, burns, and related conditions |
| AU2003220624A1 (en) | 2002-03-29 | 2003-10-13 | Maxim Pharmaceuticals, Inc. | Use of rom production and release inhibitors to treat and prevent intraocular damage |
| US20040242704A1 (en) | 2003-03-14 | 2004-12-02 | University Of Washington, Techtransfer - Invention Licensing | Stabilized mutant opsin proteins |
| EP1722766A2 (en) | 2004-02-17 | 2006-11-22 | President And Fellows Of Harvard College | Management of ophthalmologic disorders, including macular degeneration |
| US7566808B2 (en) * | 2004-02-17 | 2009-07-28 | President And Fellows Of Harvard College | Management of ophthalmologic disorders, including macular degeneration |
| KR20070011379A (ko) | 2004-03-17 | 2007-01-24 | 라스 미카엘 라르센 | 시각 사이클 억제에 의한 망막증의 예방 |
| BRPI0511396B1 (pt) | 2004-06-18 | 2021-07-27 | University Of Washington | Uso de 9-cis-retinil éster e uso de um derivado de retinal sintético |
| SI1768657T1 (sl) | 2004-06-23 | 2009-02-28 | Sirion Terapeutics Inc | Postopki in sestavki za zdravljenje oftalmičnih obolenj z derivati retinila |
| WO2006033734A2 (en) | 2004-08-18 | 2006-03-30 | Sirion Therapeutics, Inc. | Combination compositions comprising 13-cis-retinyl derivatives and uses thereof to treat opthalmic disorders |
| WO2006039551A2 (en) | 2004-09-30 | 2006-04-13 | The Regents Of The University Of California | Local administration of retinoids to treat deficiencies in dark adaptation |
| EP2187880B1 (en) | 2007-09-12 | 2013-12-18 | The Trustees of Columbia University in the City of New York | Compositions and methods for treating macular degeneration |
| JP6022746B2 (ja) | 2008-02-11 | 2016-11-09 | ユニヴァーシティ オブ ワシントン | 加齢関連性網膜機能不全の治療及び予防方法 |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3196078A (en) * | 1962-01-30 | 1965-07-20 | Ortho Pharma Corp | Process for combating retinits pigmentosa |
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