CA2769203A1 - Liver x receptor agonists - Google Patents
Liver x receptor agonists Download PDFInfo
- Publication number
- CA2769203A1 CA2769203A1 CA2769203A CA2769203A CA2769203A1 CA 2769203 A1 CA2769203 A1 CA 2769203A1 CA 2769203 A CA2769203 A CA 2769203A CA 2769203 A CA2769203 A CA 2769203A CA 2769203 A1 CA2769203 A1 CA 2769203A1
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- CA
- Canada
- Prior art keywords
- compound
- hydroxyl
- deleted
- independently
- 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.)
- Abandoned
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- 238000000034 method Methods 0.000 claims abstract description 24
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Classifications
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
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- Psychiatry (AREA)
- Child & Adolescent Psychology (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22938609P | 2009-07-29 | 2009-07-29 | |
| US61/229,386 | 2009-07-29 | ||
| PCT/US2010/043719 WO2011014661A2 (en) | 2009-07-29 | 2010-07-29 | Liver x receptor agonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2769203A1 true CA2769203A1 (en) | 2011-02-03 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2769203A Abandoned CA2769203A1 (en) | 2009-07-29 | 2010-07-29 | Liver x receptor agonists |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US8829213B2 (enExample) |
| EP (1) | EP2459581A4 (enExample) |
| JP (1) | JP2013500986A (enExample) |
| CN (1) | CN102482315A (enExample) |
| CA (1) | CA2769203A1 (enExample) |
| WO (1) | WO2011014661A2 (enExample) |
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| EP4245369A3 (en) | 2011-09-08 | 2023-11-22 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| CN103360456B (zh) * | 2012-04-04 | 2015-07-29 | 浙江大学 | 三萜类化合物及制备和应用 |
| CN103360453B (zh) * | 2012-04-04 | 2015-10-07 | 浙江大学 | 四环三萜类化合物的制备和抗衰老应用 |
| EP2759295A1 (en) | 2013-01-29 | 2014-07-30 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Foam cell specific Liver X Receptor (LXR) alpha agonist, SIRT1 inhibitors as well as p300 inhibitors as pharmaceutically active agents |
| DK3932932T3 (da) | 2013-03-13 | 2025-08-18 | Sage Therapeutics Inc | Neuroaktive sterioder og fremgangsmåder til anvendelse deraf |
| CN104072564B (zh) * | 2013-03-28 | 2016-08-17 | 广州市赛普特医药科技股份有限公司 | 2β,3α,5α-三羟基-雄甾-6-酮及其制备方法与用途 |
| JP6320861B2 (ja) * | 2013-10-16 | 2018-05-09 | 株式会社ファンケル | コレステロール吸収阻害剤 |
| AU2015204572B2 (en) | 2014-01-10 | 2020-07-30 | Inspirna, Inc. | LXR agonists and uses thereof |
| EP4306114A1 (en) | 2014-06-18 | 2024-01-17 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| EP3221332B1 (en) | 2014-11-19 | 2019-04-24 | NZP UK Limited | 5.beta.-6-alkyl-7-hydroxy-3-one steroids as intermediates for the production of steroidal fxr modulators |
| MX381239B (es) | 2014-11-19 | 2025-03-12 | Nzp Uk Ltd | Esteroides de 6.alfa.-alquil-6,7-diona como intermedios para la producción de moduladores esteroideos del receptor x farnesoide (fxr). |
| BR112017010319B1 (pt) | 2014-11-19 | 2023-04-11 | NZP UK Limited | Esteroides 6-alquil-7-hidróxi-4-en-3-ona e processo para a preparação dos mesmos |
| PL3221333T3 (pl) | 2014-11-19 | 2020-01-31 | NZP UK Limited | Steroidy, 6.alfa-alkilo-3,7-diony jako związki pośrednie do wytwarzania steroidowych modulatorów fxr |
| WO2017007832A1 (en) | 2015-07-06 | 2017-01-12 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| ES2865258T3 (es) | 2015-07-06 | 2021-10-15 | Sage Therapeutics Inc | Oxiesteroles y procedimientos de uso de los mismos |
| PE20180482A1 (es) | 2015-07-06 | 2018-03-07 | Sage Therapeutics Inc | Oxiesteroles y metodos de uso de los mismos |
| EP3397258A2 (en) * | 2015-12-30 | 2018-11-07 | Consejo Nacional De Investigaciones Cientificas Y Tecnicas (CONICET) | Use of brassinosteroid analogs for the treatment of dermal disorders by selectively modulating liver x receptors (lxr) and dermal disease treatment by brassinosteroid analogs acting as selective liver x receptor (lxr) modulators |
| EP3402477A4 (en) | 2016-01-11 | 2019-08-21 | The Rockefeller University | METHOD FOR THE TREATMENT OF DISEASES RELATED TO MYELOID-DERIVED SUPPRESSOR CELLS |
| WO2017173358A1 (en) | 2016-04-01 | 2017-10-05 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| WO2017193046A1 (en) | 2016-05-06 | 2017-11-09 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| CN106188205B (zh) * | 2016-05-06 | 2017-08-25 | 深圳以诺生物制药有限公司 | 一种罗汉果醇衍生物单体及其组合物的用途 |
| GB201608776D0 (en) | 2016-05-18 | 2016-06-29 | Dextra Lab Ltd | Methods and compounds |
| GB201608777D0 (en) | 2016-05-18 | 2016-06-29 | Dextra Lab Ltd | Compounds |
| IT201600068742A1 (it) * | 2016-07-01 | 2018-01-01 | Bar Pharmaceuticals Soc A Responsabilita Limitata | Derivati dell'acido iodesossicolico e loro uso |
| JP6966486B2 (ja) | 2016-07-07 | 2021-11-17 | セージ セラピューティクス， インコーポレイテッド | オキシステロールおよびその使用方法 |
| AU2017337121B2 (en) | 2016-09-30 | 2022-01-27 | Sage Therapeutics, Inc. | C7 substituted oxysterols and methods as NMDA modulators |
| TWI815800B (zh) | 2016-10-18 | 2023-09-21 | 美商賽吉醫療公司 | 氧固醇(oxysterol)及其使用方法 |
| MA46565A (fr) | 2016-10-18 | 2019-08-28 | Sage Therapeutics Inc | Oxystérols et leurs procédés d'utilisation |
| JP2021504315A (ja) | 2017-11-21 | 2021-02-15 | ルジェニクス，インコーポレーテッド | 多形及びその使用 |
| WO2020041673A1 (en) | 2018-08-23 | 2020-02-27 | President And Fellows Of Harvard College | Compositions and methods related to cholic acid-7-sulfate as a treatment for diabetes |
| EP3890745B1 (en) | 2018-12-04 | 2025-11-19 | President and Fellows of Harvard College | Synthetic derivatives of cholic acid 7-sulfate and uses thereof |
| JP2022514257A (ja) * | 2018-12-13 | 2022-02-10 | アイノス，インコーポレイテッド | ドライアイ疾患の治療のための局所点眼製剤におけるｌｘｒアゴニスト |
| MX2022007164A (es) | 2019-12-13 | 2022-09-12 | Inspirna Inc | Sales metálicas y usos de estas. |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2698853A (en) | 1951-08-11 | 1955-01-04 | Monsanto Chemicals | Oxidation of steroids |
| FR1482102A (fr) | 1966-03-31 | 1967-05-26 | Centre Nat Rech Scient | Nouveaux dérivés de stéroïdes et procédé de préparation |
| US3784598A (en) | 1972-01-20 | 1974-01-08 | Ciba Geigy Corp | Process for the conversion of a 3-hydroxy-5,6-oxido group of a steroid into a delta4-3-oxo group |
| JPS4976857A (enExample) | 1972-12-06 | 1974-07-24 | ||
| US3963765A (en) | 1973-04-01 | 1976-06-15 | Yehuda Mazur | Preparation of derivatives of cholesterol |
| US3887545A (en) | 1973-11-12 | 1975-06-03 | Hoffmann La Roche | Synthesis of 1{60 -hydroxylated cholesterol derivatives |
| US4006172A (en) | 1976-04-26 | 1977-02-01 | The Upjohn Company | Process for 7-keto-Δ5 -steroids |
| US4125544A (en) | 1977-06-09 | 1978-11-14 | G. D. Searle | 20/22/23/24-Oxa-7-oxocholesterols and esters thereof |
| AU520334B2 (en) | 1977-08-29 | 1982-01-28 | G.D. Searle & Co. | 25-alkylcholesterol derivatives |
| US4193930A (en) | 1977-08-29 | 1980-03-18 | G. D. Searle & Co. | 25-Alkyl-3β-hydroxycholest-5-en-7-ones and esters thereof |
| JPS563000A (en) | 1979-06-20 | 1981-01-13 | Green Cross Corp:The | Water-soluble cholesterol derivative |
| US4639420A (en) | 1984-11-21 | 1987-01-27 | Schaffner Carl P | Method for the immunoanalysis of cholesterol epoxides |
| US4917998A (en) * | 1986-05-06 | 1990-04-17 | Epitope, Inc. | Method of detecting AIDS virus infection |
| IT1212141B (it) | 1987-06-03 | 1989-11-08 | So Ri Far S R L | Composizioni farmaceutiche per la prevenzione e terapia della calcolosi delle vie biliari e della dispepsia biliare. |
| US5151545A (en) | 1987-10-13 | 1992-09-29 | Pfizer Inc. | 3,5-dihydroxy-6,8-nonadienoic acids and derivatives as hypocholesterolemic agents |
| US5562910A (en) | 1989-09-25 | 1996-10-08 | University Of Utah Research Foundation | Vaccine compositions and method for enhancing an immune response |
| US5424463A (en) | 1990-08-29 | 1995-06-13 | Humanetics Corporation | Δ5-androstenes useful for promoting weight maintenance or weight loss and treatment process |
| JPH0749438B2 (ja) | 1990-10-31 | 1995-05-31 | 東京田辺製薬株式会社 | タウリン抱合型胆汁酸の精製方法 |
| IL105050A0 (en) | 1992-03-27 | 1993-07-08 | Lilly Co Eli | Steroid derivatives |
| IT1255241B (it) | 1992-07-22 | 1995-10-20 | Simos Contos | Derivato di acido biliare e suo uso in terapia |
| IT1255486B (it) | 1992-08-04 | 1995-11-06 | Erregierre Ind Chim | Processo per preparare gli acidi biliari coniugati con la taurina |
| US5482935A (en) | 1993-01-05 | 1996-01-09 | American Home Product Corporation | Anti-atherosclerotic use of 17 alpha-dihydroequilin |
| TW289757B (enExample) | 1993-05-08 | 1996-11-01 | Hoechst Ag | |
| IT1270853B (it) | 1993-05-20 | 1997-05-13 | Sanofi Elf | Procedimento per la preparazione di derivati taurocolanici |
| CN1055929C (zh) | 1993-09-20 | 2000-08-30 | 中国科学院上海有机化学研究所 | 三氟甲基甾体化合物及其制备方法 |
| IT1274000B (it) | 1994-04-06 | 1997-07-14 | Alfa Wassermann Spa | Derivati di acidi biliari utili nella terapia della calcolosi biliare da colesterolo e nelle patologie indotte da colestasi |
| HU223613B1 (hu) | 1994-05-19 | 2004-10-28 | Merck & Co. Inc. | Új eljárás delta5 szteroidok 7-oxo-származékká történő oxidálására |
| US5583239A (en) | 1995-05-30 | 1996-12-10 | Lehigh University | Antimicrobial sterol conjugates |
| WO1998032444A1 (en) | 1997-01-24 | 1998-07-30 | The Regents Of The University Of California | USE OF FXR, PPARα AND LXRα ACTIVATORS TO RESTORE BARRIER FUNCTION, PROMOTE EPIDERMAL DIFFERENTIATION AND INHIBIT PROLIFERATION |
| US6060465A (en) | 1997-02-06 | 2000-05-09 | Miljkovic; Dusan | Bile acids and their derivatives as glycoregulatory agents |
| CA2356887A1 (en) | 1998-12-23 | 2000-06-29 | Glaxo Group Limited | Assays for ligands for nuclear receptors |
| AU2409600A (en) | 1999-01-07 | 2000-07-24 | Tularik Inc. | Fxr receptor-mediated modulation of cholesterol metabolism |
| BR0010197A (pt) | 1999-04-30 | 2002-07-16 | Arch Dev Corp | Derivados de esteróides |
| JP2002030097A (ja) * | 2000-07-11 | 2002-01-29 | Kyorin Pharmaceut Co Ltd | ステロイド誘導体の製造方法 |
| JP2002030096A (ja) * | 2000-07-11 | 2002-01-29 | Kyorin Pharmaceut Co Ltd | 神経細胞突起再生剤及びその製造方法 |
| DE10105041A1 (de) | 2001-02-05 | 2002-08-14 | Tell Pharm Ag Hergiswil | Tripeptide und Tripeptid-Derivate für die Behandlung neurodegenerativer Krankheiten |
| CA2438221A1 (en) | 2001-02-08 | 2002-08-15 | The University Of Chicago | Steroidal derivatives |
| US7078396B2 (en) | 2001-05-03 | 2006-07-18 | Arch Development Corporation | Method of treating disorder related to high cholesterol concentration |
| ES2296928T3 (es) * | 2001-05-03 | 2008-05-01 | The University Of Chicago | Receptores x hepaticos. |
| WO2003039480A2 (en) | 2001-11-08 | 2003-05-15 | The University Of Chicago | Method of treating disorder related to high cholesterol concentration |
| AU2003228485A1 (en) | 2002-04-12 | 2003-10-27 | The University Of Chicago | Farnesoid x-activated receptor agonists |
| US20070032464A1 (en) * | 2004-10-08 | 2007-02-08 | Shutsung Liao | Methods of treating cancers |
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- 2010-07-29 US US12/846,326 patent/US8829213B2/en not_active Expired - Fee Related
- 2010-07-29 CN CN2010800336173A patent/CN102482315A/zh active Pending
- 2010-07-29 WO PCT/US2010/043719 patent/WO2011014661A2/en not_active Ceased
- 2010-07-29 JP JP2012523043A patent/JP2013500986A/ja active Pending
- 2010-07-29 CA CA2769203A patent/CA2769203A1/en not_active Abandoned
- 2010-07-29 EP EP10805047A patent/EP2459581A4/en not_active Withdrawn
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| US20110059932A1 (en) | 2011-03-10 |
| CN102482315A (zh) | 2012-05-30 |
| EP2459581A4 (en) | 2012-12-26 |
| JP2013500986A (ja) | 2013-01-10 |
| EP2459581A2 (en) | 2012-06-06 |
| US8829213B2 (en) | 2014-09-09 |
| WO2011014661A3 (en) | 2011-06-09 |
| WO2011014661A2 (en) | 2011-02-03 |
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