CA2794018C - Compositions and methods for the treatment of degenerative diseases - Google Patents
Compositions and methods for the treatment of degenerative diseases Download PDFInfo
- Publication number
- CA2794018C CA2794018C CA2794018A CA2794018A CA2794018C CA 2794018 C CA2794018 C CA 2794018C CA 2794018 A CA2794018 A CA 2794018A CA 2794018 A CA2794018 A CA 2794018A CA 2794018 C CA2794018 C CA 2794018C
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- CA
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- Prior art keywords
- compound
- pharmaceutically acceptable
- acceptable salt
- administration
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
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- C07D401/06—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 linked by a carbon chain containing only aliphatic carbon atoms
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- 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
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- 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
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Landscapes
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- Engineering & Computer Science (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
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| US31718510P | 2010-03-24 | 2010-03-24 | |
| US61/317,185 | 2010-03-24 | ||
| PCT/US2011/029846 WO2011119869A1 (en) | 2010-03-24 | 2011-03-24 | Compositions and methods for the treatment of degenerative diseases |
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| EP2906946A1 (en) | 2012-10-09 | 2015-08-19 | The Procter & Gamble Company | Method of identifying or evaluating beneficial actives and compositions containing the same |
| WO2014059009A1 (en) | 2012-10-09 | 2014-04-17 | The Procter & Gamble Company | Method of identifying synergistic cosmetic combinations |
| GEP201706757B (en) | 2012-12-21 | 2017-10-25 | Alios Biopharma Inc | Substituted nucleosides, nucleotides and analogs thereof |
| US20140275178A1 (en) * | 2013-03-13 | 2014-09-18 | Musc Foundation For Research Development | Thiazole compounds, compositions and methods for treatment of degenerative diseases and disorders |
| US8921401B2 (en) | 2013-02-07 | 2014-12-30 | Musc Foundation For Research Development | Pyrazole compounds, compositions and methods for treatment of degenerative diseases and disorders |
| US9079853B2 (en) * | 2013-02-07 | 2015-07-14 | Musc Foundation For Research Development | Isatin compounds, compositions and methods for treatment of degenerative diseases and disorders |
| CA3126082A1 (en) | 2013-03-14 | 2014-09-18 | Universite Laval | Use of electroretinography (erg) for the assessment of psychiatric disorders |
| EP3180335B1 (en) | 2014-08-11 | 2021-05-05 | Angion Biomedica Corporation | Cytochrome p450 inhibitors and uses thereof |
| CN107531631B (zh) | 2014-12-31 | 2021-09-03 | 安吉昂生物医药公司 | 用于治疗疾病的方法和药剂 |
| CN104803946A (zh) * | 2015-03-03 | 2015-07-29 | 佛山市赛维斯医药科技有限公司 | 含腈基噻唑和环戊二烯结构的ptp1b抑制剂及其用途 |
| AU2016254049A1 (en) * | 2015-04-30 | 2017-11-02 | Musc Foundation For Research Development | Oxindole compounds and pharmaceutical compositions thereof |
| US10421756B2 (en) | 2015-07-06 | 2019-09-24 | Rodin Therapeutics, Inc. | Heterobicyclic N-aminophenyl-amides as inhibitors of histone deacetylase |
| LT3319959T (lt) | 2015-07-06 | 2021-12-27 | Alkermes, Inc. | Histono deacetilazės hetero-halogeno inhibitoriai |
| US10967019B2 (en) | 2015-11-30 | 2021-04-06 | Taiwan Mitochondrion Applied Technology Co., Ltd. | Method for protecting mitochondria in retina cell |
| TWI666023B (zh) * | 2016-09-26 | 2019-07-21 | 台灣粒線體應用技術股份有限公司 | 餘甘子萃取物用於製備保護視網膜中粒線體的醫藥組合物的用途 |
| KR20240036709A (ko) * | 2016-03-11 | 2024-03-20 | 에이씨 이뮨 에스에이 | 진단 및 치료를 위한 바이사이클릭 화합물 |
| ES2909086T3 (es) | 2017-01-11 | 2022-05-05 | Alkermes Inc | Inhibidores bicíclicos de histona desacetilasa |
| SG11202000970WA (en) | 2017-08-07 | 2020-02-27 | Rodin Therapeutics Inc | Bicyclic inhibitors of histone deacetylase |
| CN114026085A (zh) | 2019-04-11 | 2022-02-08 | 安吉昂生物医药公司 | (e)-3-[2-(2-噻吩基)乙烯基]-1h-吡唑的固体形式 |
| AU2021224588B2 (en) | 2020-02-18 | 2024-07-18 | Gilead Sciences, Inc. | Antiviral compounds |
| TWI794742B (zh) | 2020-02-18 | 2023-03-01 | 美商基利科學股份有限公司 | 抗病毒化合物 |
| TWI874791B (zh) | 2020-02-18 | 2025-03-01 | 美商基利科學股份有限公司 | 抗病毒化合物 |
| JP7830341B2 (ja) | 2020-03-26 | 2026-03-16 | ディアメンティス・インコーポレイテッド | 網膜信号データを処理し、状態を識別するためのシステムおよび方法 |
| JP7688152B2 (ja) | 2021-04-16 | 2025-06-03 | ギリアード サイエンシーズ， インコーポレイテッド | アミドを使用してカルバヌクレオシドを調製する方法 |
| JP7719954B2 (ja) | 2021-08-18 | 2025-08-06 | ギリアード サイエンシーズ， インコーポレイテッド | リン脂質化合物並びにその製造方法及び使用方法 |
| IL314207A (en) * | 2022-01-26 | 2024-09-01 | Suzhou Genhouse Bio Co Ltd | MAT2A inhibitor for the treatment of MTAP deletion type cancer |
| JP2025507352A (ja) | 2022-02-09 | 2025-03-18 | ディアメンティス・インコーポレイテッド | 網膜刺激および／または網膜信号データの収集のためのシステムと方法 |
| AR130747A1 (es) * | 2022-10-13 | 2025-01-15 | Hanmi Pharmaceutical Co Ltd | Compuestos novedosos derivados de triciclo y usos de los mismos |
| KR20250121114A (ko) | 2022-12-16 | 2025-08-11 | 아스트라제네카 아베 | 2,6,9-삼치환된 퓨린 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA962269A (en) * | 1971-05-05 | 1975-02-04 | Uniroyal Ltd. | Thiazoles, and their use as insecticides |
| US3852293A (en) * | 1972-06-21 | 1974-12-03 | Uniroyal Inc | 4-phenyl-2-(3-pyridyl)-thiazole carboxamides |
| JPS57183768A (en) * | 1981-05-06 | 1982-11-12 | Kanto Ishi Pharma Co Ltd | 4-methyl-5-(o-carboxyphenyl)carbamoylthiazole derivative and its preparation |
| US4788207A (en) * | 1988-02-29 | 1988-11-29 | Fmc Corporation | Photoactivated miticidal and insecticidal ethynylthiazoles |
| DE19845402B4 (de) * | 1998-10-02 | 2005-04-07 | Aventis Pharma Deutschland Gmbh | Mit Heterocyclen substituierte Propanolaminderivate, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| TWI243164B (en) * | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
| EP1402900A1 (en) * | 2001-06-11 | 2004-03-31 | Takeda Chemical Industries, Ltd. | Medicinal compositions |
| DE60324898D1 (de) * | 2002-02-25 | 2009-01-08 | Lilly Co Eli | Modulatoren von peroxisome proliferator-aktivierten rezeptoren |
| WO2003101927A1 (en) * | 2002-05-31 | 2003-12-11 | Proteotech, Inc. | Compounds, compositions and methods for the treatment of amyloid diseases and synucleinopathies such as alzheimer's disease, type 2 diabetes, and parkinson's disease |
| WO2006094237A2 (en) * | 2005-03-03 | 2006-09-08 | Sirtris Pharmaceuticals, Inc. | Acridine and quinoline dervatives as sirtuin modulators |
| AR056317A1 (es) * | 2005-04-20 | 2007-10-03 | Xenon Pharmaceuticals Inc | Compuestos de oxindol y composicion farmaceutica |
| GB0701426D0 (en) * | 2007-01-25 | 2007-03-07 | Univ Sheffield | Compounds and their use |
| CL2008001822A1 (es) * | 2007-06-20 | 2009-03-13 | Sirtris Pharmaceuticals Inc | Compuestos derivados de tiazolo[5,4-b]piridina; composicion farmaceutica que comprende a dichos compuestos; y uso del compuesto en el tratamiento de la resistencia a la insulina, sindrome metabolico, diabetes, entre otras. |
| RU2007139634A (ru) * | 2007-10-25 | 2009-04-27 | Сергей Олегович Бачурин (RU) | Новые тиазол-, триазол- или оксадиазол-содержащие тетрациклические соединения |
| WO2009064388A2 (en) * | 2007-11-09 | 2009-05-22 | Liu Jun O | Inhibitors of human methionine aminopeptidase 1 and methods of treating disorders |
-
2011
- 2011-03-24 US US13/636,754 patent/US20130137728A1/en not_active Abandoned
- 2011-03-24 AU AU2011232347A patent/AU2011232347B2/en not_active Ceased
- 2011-03-24 EP EP11715106A patent/EP2550260A1/en not_active Withdrawn
- 2011-03-24 WO PCT/US2011/029846 patent/WO2011119869A1/en not_active Ceased
- 2011-03-24 JP JP2013501494A patent/JP2013522376A/ja active Pending
- 2011-03-24 CA CA2794018A patent/CA2794018C/en not_active Expired - Fee Related
-
2015
- 2015-09-28 JP JP2015189524A patent/JP2015232051A/ja active Pending
-
2016
- 2016-01-15 US US14/996,662 patent/US20160237074A1/en not_active Abandoned
- 2016-08-09 JP JP2016156126A patent/JP2016188257A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CA2794018A1 (en) | 2011-09-29 |
| US20130137728A1 (en) | 2013-05-30 |
| WO2011119869A1 (en) | 2011-09-29 |
| JP2016188257A (ja) | 2016-11-04 |
| JP2015232051A (ja) | 2015-12-24 |
| AU2011232347B2 (en) | 2015-08-06 |
| EP2550260A1 (en) | 2013-01-30 |
| AU2011232347A1 (en) | 2012-10-04 |
| US20160237074A1 (en) | 2016-08-18 |
| JP2013522376A (ja) | 2013-06-13 |
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| EEER | Examination request | ||
| MKLA | Lapsed |
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