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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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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- 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
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- 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
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- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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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 |
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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 |
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| 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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| HUE062616T2 (hu) | 2011-09-08 | 2023-11-28 | Sage Therapeutics Inc | Neuroaktív szteroidok, készítmények és alkalmazásaik |
| 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 |
| CN103360456B (zh) * | 2012-04-04 | 2015-07-29 | 浙江大学 | 三萜类化合物及制备和应用 |
| 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 |
| FI3932932T3 (fi) | 2013-03-13 | 2025-10-15 | Sage Therapeutics Inc | Neuroaktiivisia steroideja ja niiden käyttömenetelmiä |
| 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 |
| JP6628745B2 (ja) | 2014-06-18 | 2020-01-15 | 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 |
| EA033427B1 (ru) | 2014-11-19 | 2019-10-31 | Nzp Uk Ltd | 6-алкил-7-гидрокси-4-ен-3-оновые стероиды в качестве промежуточных соединений для получения стероидных модуляторов fxr |
| KR102526632B1 (ko) | 2014-11-19 | 2023-04-27 | 엔제트피 유케이 리미티드 | 스테로이드 FXR 조절인자를 제조하기 위한 중간체로서의 5β-6-알킬-7-하이드록시-3-온 스테로이드 |
| ES2748692T3 (es) | 2014-11-19 | 2020-03-17 | Nzp Uk Ltd | Esteroides 6.alfa.-alquil-3,7-diona como intermedios para la producción de moduladores FXR de esteroides |
| JP6698085B2 (ja) | 2014-11-19 | 2020-05-27 | エヌゼットピー ユーケー リミテッド | ステロイドＦＸＲモジュレーター製造のための中間体としての６α−アルキル−６，７−ジオン−ステロイド |
| PT3319611T (pt) | 2015-07-06 | 2021-04-22 | Sage Therapeutics Inc | Oxisteróis e métodos de utilização dos mesmos |
| WO2017007832A1 (en) | 2015-07-06 | 2017-01-12 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| DK3812392T3 (da) | 2015-07-06 | 2025-07-21 | Sage Therapeutics Inc | Oxysteroler og fremgangsmåder til anvendelse deraf |
| 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 |
| AU2017207291B2 (en) | 2016-01-11 | 2023-06-15 | The Rockefeller University | Methods for the treatment of myeloid derived suppressor cells related disorders |
| ES2921010T3 (es) | 2016-04-01 | 2022-08-16 | Sage Therapeutics Inc | Oxisteroles y procedimientos de uso de los mismos |
| 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 |
| WO2018009867A1 (en) | 2016-07-07 | 2018-01-11 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| MA46351A (fr) | 2016-09-30 | 2021-06-02 | Sage Therapeutics Inc | Oxystérols substitués en c7 et procédés en tant que modulateurs nmda |
| KR102521573B1 (ko) | 2016-10-18 | 2023-04-14 | 세이지 테라퓨틱스, 인크. | 옥시스테롤 및 그의 사용 방법 |
| DK3529257T3 (da) | 2016-10-18 | 2023-08-07 | Sage Therapeutics Inc | Oxysteroler og fremgangsmåder til anvendelse deraf |
| EP3713575A4 (en) | 2017-11-21 | 2021-08-25 | Rgenix, Inc. | POLYMORPHS AND THEIR USES |
| US12186329B2 (en) | 2018-08-23 | 2025-01-07 | President And Fellows Of Harvard College | Compositions and methods related to cholic acid 7-sulfate as a treatment for diabetes |
| WO2020117945A1 (en) | 2018-12-04 | 2020-06-11 | President And Fellows Of Harvard College | Synthetic derivatives of cholic acid 7-sulfate and uses thereof |
| WO2020123869A1 (en) * | 2018-12-13 | 2020-06-18 | eyeNOS, Inc. | Lxr agonist in topical ophthalmic formulation for treatment of dry-eye disorder |
| CN120757601A (zh) | 2019-05-10 | 2025-10-10 | 哈佛大学的校长及成员们 | 肠道细菌胆汁酸代谢的小分子调节剂 |
| JP7689964B2 (ja) | 2019-12-13 | 2025-06-09 | インスピルナ，インコーポレーテッド | 金属塩及びその使用 |
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 |
| CH643566A5 (de) | 1977-08-29 | 1984-06-15 | Searle & Co | 25-alkylcholesterin-derivate. |
| 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. |
| WO1989003212A1 (en) | 1987-10-13 | 1989-04-20 | 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 |
| US5506223A (en) | 1990-08-29 | 1996-04-09 | 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 |
| CN1152316A (zh) | 1994-05-19 | 1997-06-18 | 麦克公司 | 具有烯丙基的甾族化合物的氧化 |
| US5583239A (en) | 1995-05-30 | 1996-12-10 | Lehigh University | Antimicrobial sterol conjugates |
| EP1019059A4 (en) | 1997-01-24 | 2004-01-14 | Univ California | USE OF FXR, PPAR-ALPHA AND LXR-ALPHA ACTIVATORS TO RESTORE THE BARRIER FUNCTION, TO PROMOTE EPIDERMIS DIFFERENTIATION, AND TO PROLIFERATE |
| US6060465A (en) | 1997-02-06 | 2000-05-09 | Miljkovic; Dusan | Bile acids and their derivatives as glycoregulatory agents |
| ES2326850T3 (es) | 1998-12-23 | 2009-10-20 | Glaxo Group Limited | Ensayos para ligandos de receptores nucleares. |
| US6465258B1 (en) | 1999-01-07 | 2002-10-15 | Tularik, Inc. | FXR receptor-mediated modulation cholesterol metabolism |
| JP2002543216A (ja) | 1999-04-30 | 2002-12-17 | アーチ ディベロップメント コーポレイション | ステロイド誘導体 |
| 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 |
| WO2002062302A2 (en) | 2001-02-08 | 2002-08-15 | The University Of Chicago | Steroidal derivatives |
| JP4309661B2 (ja) | 2001-05-03 | 2009-08-05 | ザ ユニバーシティー オブ シカゴ | 肝臓ｘ受容体 |
| US7078396B2 (en) | 2001-05-03 | 2006-07-18 | Arch Development Corporation | Method of treating disorder related to high cholesterol concentration |
| 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 CA CA2769203A patent/CA2769203A1/en not_active Abandoned
- 2010-07-29 WO PCT/US2010/043719 patent/WO2011014661A2/en not_active Ceased
- 2010-07-29 CN CN2010800336173A patent/CN102482315A/zh active Pending
- 2010-07-29 US US12/846,326 patent/US8829213B2/en not_active Expired - Fee Related
- 2010-07-29 EP EP10805047A patent/EP2459581A4/en not_active Withdrawn
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| US20110059932A1 (en) | 2011-03-10 |
| WO2011014661A2 (en) | 2011-02-03 |
| US8829213B2 (en) | 2014-09-09 |
| JP2013500986A (ja) | 2013-01-10 |
| EP2459581A4 (en) | 2012-12-26 |
| CN102482315A (zh) | 2012-05-30 |
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