CA2884802A1 - Galactoside inhibitor of galectin-3 and its use for treating pulmonary fibrosis - Google Patents
Galactoside inhibitor of galectin-3 and its use for treating pulmonary fibrosis Download PDFInfo
- Publication number
- CA2884802A1 CA2884802A1 CA2884802A CA2884802A CA2884802A1 CA 2884802 A1 CA2884802 A1 CA 2884802A1 CA 2884802 A CA2884802 A CA 2884802A CA 2884802 A CA2884802 A CA 2884802A CA 2884802 A1 CA2884802 A1 CA 2884802A1
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- Prior art keywords
- composition
- compound
- formula
- nebulizer
- galectin
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- Abandoned
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Landscapes
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Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2884802A CA2884802A1 (en) | 2012-10-31 | 2013-10-30 | Galactoside inhibitor of galectin-3 and its use for treating pulmonary fibrosis |
Applications Claiming Priority (10)
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|---|---|---|---|
| US201261720641P | 2012-10-31 | 2012-10-31 | |
| US61/720,641 | 2012-10-31 | ||
| CA2794066 | 2012-10-31 | ||
| CA2794066A CA2794066C (en) | 2012-10-31 | 2012-10-31 | Galactoside inhibitor of galectins |
| CA2795793 | 2012-11-15 | ||
| CA2795753A CA2795753A1 (en) | 2012-10-31 | 2012-11-15 | Novel galactoside inhibitor of galectins |
| US13/832,672 US9243021B2 (en) | 2012-10-31 | 2013-03-15 | Galactoside inhibitor of galectins |
| US13/832,672 | 2013-03-15 | ||
| PCT/EP2013/072691 WO2014067986A1 (en) | 2012-10-31 | 2013-10-30 | Galactoside inhibitor of galectin-3 and its use for treating pulmonary fibrosis |
| CA2884802A CA2884802A1 (en) | 2012-10-31 | 2013-10-30 | Galactoside inhibitor of galectin-3 and its use for treating pulmonary fibrosis |
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| CA2884802A1 true CA2884802A1 (en) | 2014-05-08 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA2884802A Abandoned CA2884802A1 (en) | 2012-10-31 | 2013-10-30 | Galactoside inhibitor of galectin-3 and its use for treating pulmonary fibrosis |
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|---|---|
| EP (2) | EP3278805A1 (https=) |
| JP (1) | JP2015535233A (https=) |
| CN (1) | CN104755088A (https=) |
| CA (1) | CA2884802A1 (https=) |
| ES (1) | ES2817888T3 (https=) |
| IN (1) | IN2015DN02573A (https=) |
| WO (1) | WO2014067986A1 (https=) |
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| US9243021B2 (en) | 2012-10-31 | 2016-01-26 | Galecto Biotech Ab | Galactoside inhibitor of galectins |
| EP2620443A1 (en) | 2012-01-25 | 2013-07-31 | Galecto Biotech AB | Novel galactoside inhibitors of galectins |
| JP6735680B2 (ja) | 2014-07-09 | 2020-08-05 | ガレクト バイオテック エービー | ガレクチンの新規ハイブリッドガラクトシド阻害剤 |
| JP6707548B2 (ja) | 2015-01-16 | 2020-06-10 | ガレクト・バイオテック・エイビイ | ガレクチンの新規なガラクトシド阻害剤 |
| CA2970062C (en) * | 2015-01-30 | 2023-02-28 | Galecto Biotech Ab | Alpha-d-galactoside inhibitors of galectins |
| WO2016180483A1 (en) * | 2015-05-12 | 2016-11-17 | Galecto Biotech Ab | Once-daily treatment of pulmonary fibrosis |
| JP6915956B2 (ja) * | 2015-05-15 | 2021-08-11 | ガレクト・バイオテック・エイビイ | 肺線維症の１日１回の治療 |
| WO2017019770A1 (en) * | 2015-07-27 | 2017-02-02 | Wayne State University | Compositions and methods relating to galectin detection |
| CA3000924A1 (en) | 2015-11-09 | 2017-05-18 | Galecto Biotech Ab | Novel galactoside inhibitors of galectins |
| EP3896075A1 (en) | 2015-12-18 | 2021-10-20 | Galecto Biotech AB | Polymorphic forms and process |
| MX394409B (es) * | 2016-03-04 | 2025-03-24 | Galectin Sciences Llc | Compuestos de seleno-galactosida para la prevención y el tratamiento de las enfermedades asociadas con galectina y el uso de los mismos. |
| US10988502B2 (en) * | 2016-07-12 | 2021-04-27 | Galecto Biotech Ab | Alpha-D-galactoside inhibitors of galectins |
| CA3025867A1 (en) * | 2016-07-12 | 2018-01-18 | Galecto Biotech Ab | Alpha-d-galactoside inhibitors of galectins |
| EP3621973A4 (en) | 2017-05-12 | 2021-10-27 | Galectin Sciences, LLC | COMPOUNDS FOR THE PREVENTION AND TREATMENT OF DISEASES AND USES THEREOF |
| WO2019067702A1 (en) | 2017-09-27 | 2019-04-04 | Bristol-Myers Squibb Company | INHIBITORS WITH SMALL MOLECULES OF GALECTIN-3 |
| US11072626B2 (en) | 2017-10-11 | 2021-07-27 | Bristol-Myers Squibb Company | Small molecule inhibitors of Galectin-3 |
| KR20200104889A (ko) | 2017-12-29 | 2020-09-04 | 글리코미메틱스, 인크. | E-셀렉틴 및 갈렉틴-3의 이종이기능성 억제제 |
| JP2021510692A (ja) | 2018-01-10 | 2021-04-30 | ガレクト バイオテック エービー | ガレクチンの新規なガラクトシド阻害剤 |
| EP3793545A4 (en) * | 2018-05-17 | 2022-04-06 | Actuate Therapeutics Inc. | TREATMENT OF IDIOPATHIC PULMONARY FIBROSIS WITH BETA INHIBITORS IN THE FORM OF GLYCOGEN SYNTHASE KINASE 3 |
| CN112292386B (zh) * | 2018-06-15 | 2024-06-11 | 百时美施贵宝公司 | 作为半乳凝素-3抑制剂的基于四氢吡喃的硫代二糖模拟物 |
| US20210138080A1 (en) * | 2018-06-29 | 2021-05-13 | Glykos Biomedical Oy | Conjugates |
| JP2022508720A (ja) | 2018-10-15 | 2022-01-19 | ガレクト バイオテック エービー | ガレクチンのガラクトシド阻害剤 |
| CN113286632A (zh) | 2018-10-15 | 2021-08-20 | 格莱克特生物技术公司 | 半乳糖凝集素的半乳糖苷抑制剂前药 |
| WO2020104335A1 (en) | 2018-11-21 | 2020-05-28 | Galecto Biotech Ab | Alpha-d-galactoside inhibitors of galectins |
| KR20210100139A (ko) | 2018-12-06 | 2021-08-13 | 브리스톨-마이어스 스큅 컴퍼니 | 갈렉틴-3의 소분자 억제제 |
| CA3122321A1 (en) | 2018-12-27 | 2020-07-02 | Glycomimetics, Inc. | Galectin-3 inhibiting c-glycosides |
| US11845771B2 (en) | 2018-12-27 | 2023-12-19 | Glycomimetics, Inc. | Heterobifunctional inhibitors of E-selectin and galectin-3 |
| EP3947407B1 (en) | 2019-03-26 | 2024-06-12 | Bristol-Myers Squibb Company | Small molecule inhibitors of galectin-3 |
| US12269819B2 (en) | 2019-04-10 | 2025-04-08 | Bristol-Myers Squibb Company | Small molecule inhibitors of Galectin-3 |
| US12291547B2 (en) | 2019-06-14 | 2025-05-06 | UNIVERSITé LAVAL | Synthesis of 3-azido-3-deoxy-D-galactopyranose |
| CN114222749A (zh) * | 2019-06-24 | 2022-03-22 | 格莱克特生物技术公司 | 3,3′-二脱氧-3,3′-双-[4-(3-氟苯基)-1H-1,2,3-三唑-1-基]-1,1′-磺胺二基-二-β-D-吡喃半乳糖苷的大规模方法 |
| US12410207B2 (en) | 2019-07-03 | 2025-09-09 | Galecto Biotech Ab | Galactoside inhibitor of galectins |
| JP7674276B2 (ja) | 2019-07-03 | 2025-05-09 | ガレクト バイオテック エービー | ガレクチンの新規なガラクトシド阻害剤 |
| WO2021004940A1 (en) | 2019-07-05 | 2021-01-14 | Galecto Biotech Ab | Novel galactoside inhibitor of galectins |
| CN114206893A (zh) | 2019-08-09 | 2022-03-18 | 爱杜西亚药品有限公司 | (杂)芳基-甲基-硫代-β-D-吡喃半乳糖苷衍生物 |
| WO2021028323A1 (en) | 2019-08-09 | 2021-02-18 | Idorsia Pharmaceuticals Ltd | (2-acetamidyl)thio-beta-d-galactopyranoside derivatives |
| MA56883B1 (fr) | 2019-08-15 | 2025-04-30 | Idorsia Pharmaceuticals Ltd | Dérivés de 2-hydroxycycloalcane-1-carbamoyle |
| CN114585619B (zh) | 2019-08-29 | 2024-09-27 | 爱杜西亚药品有限公司 | α-D-吡喃半乳糖苷衍生物 |
| WO2021123506A1 (en) | 2019-12-18 | 2021-06-24 | Glykos Biomedical Oy | Stabile conjugate |
| WO2021195020A1 (en) * | 2020-03-23 | 2021-09-30 | G3 Pharmaceuticals, Inc. | Methods and compositions for preventing and treating fibrosis resulting from a coronavirus infection |
| JP2023519952A (ja) | 2020-03-31 | 2023-05-15 | ガレクト バイオテック エービー | １，２，４，６－テトラ－ｏ－アセチル－３－アジド－３－デオキシ－ｄ－ガラクトピラノシドを調製するための大規模方法 |
| US12275720B2 (en) | 2020-05-05 | 2025-04-15 | Bristol-Myers Squibb Company | Small molecule inhibitors of galectin-3 |
| US12286424B2 (en) | 2020-05-11 | 2025-04-29 | Bristol-Myers Squibb Company | Small molecule inhibitors of galectin-3 |
| KR20230018431A (ko) | 2020-05-28 | 2023-02-07 | 브리스톨-마이어스 스큅 컴퍼니 | 갈렉틴-3 억제제 |
| US12312362B2 (en) | 2020-10-06 | 2025-05-27 | Idorsia Pharmaceuticals Ltd | Spiro derivatives of Alpha-D-galactopyranosides |
| EP4237419A1 (en) | 2020-11-02 | 2023-09-06 | Idorsia Pharmaceuticals Ltd | Galectin-3 inhibiting 2-hydroxycycloalkane-1 -carbamoyl derivatives |
| CN116806219A (zh) | 2021-02-09 | 2023-09-26 | 爱杜西亚药品有限公司 | 羟基杂环烷-氨甲酰基衍生物 |
| RS67032B1 (sr) | 2021-03-03 | 2025-08-29 | Idorsia Pharmaceuticals Ltd | Alfa-d-galaktopiranozidni derivati supstituisani triazolil-metilom |
| WO2025111704A1 (en) * | 2023-12-01 | 2025-06-05 | UNIVERSITé LAVAL | Selective inhibitors of galectin-3 |
Family Cites Families (19)
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| US5152456A (en) | 1989-12-12 | 1992-10-06 | Bespak, Plc | Dispensing apparatus having a perforate outlet member and a vibrating device |
| GB9027234D0 (en) | 1990-12-15 | 1991-02-06 | Harris Pharma Ltd | An inhalation device |
| DE69230613T2 (de) | 1991-07-02 | 2000-12-28 | Inhale Inc | Verfahren und vorrichtung zum abgeben von medikamenten in aerosolform |
| EP0938907B1 (en) | 1996-01-03 | 2001-12-05 | Glaxo Group Limited | Inhalation device |
| DE19726110C2 (de) | 1997-06-20 | 1999-07-22 | Draegerwerk Ag | Aerosolgenerator für Beatmungssysteme |
| US6962151B1 (en) | 1999-11-05 | 2005-11-08 | Pari GmbH Spezialisten für effektive Inhalation | Inhalation nebulizer |
| DE10102846B4 (de) | 2001-01-23 | 2012-04-12 | Pari Pharma Gmbh | Aerosolgenerator |
| ATE269735T1 (de) | 2001-10-18 | 2004-07-15 | Pari Gmbh | Inhalationstherapievorrichtung |
| JP2005513031A (ja) * | 2001-11-26 | 2005-05-12 | アラクノーバ・セラピューティックス・リミテッド | 肺線維症の処置のためのｐｐａｒアクチベーターの使用 |
| DE60235883D1 (de) | 2002-08-02 | 2010-05-20 | Pari Pharma Gmbh | Vorrichtung zur Erzeugung von Flüssigkeitströpfchen |
| DE10250625A1 (de) | 2002-10-30 | 2004-05-19 | Pari GmbH Spezialisten für effektive Inhalation | Inhalationstherapievorrichtung |
| DE10257381B4 (de) | 2002-12-09 | 2006-09-14 | Pari GmbH Spezialisten für effektive Inhalation | Inhalationstherapievorrichtung |
| SE0401301D0 (sv) | 2004-05-21 | 2004-05-21 | Forskarpatent I Syd Ab | Novel 3-triazolyl-galactoside inhibitors of galectins |
| SE0401300D0 (sv) | 2004-05-21 | 2004-05-21 | Forskarpatent I Syd Ab | Novel Galactoside Inhibitors of Galectins |
| US20080249144A1 (en) * | 2004-07-22 | 2008-10-09 | Kaken Pharmaceuitical Co., Ltd. | Preventive or Therapeutic Agent for Chronic Inflammatory Lung Disease |
| ES2652488T3 (es) | 2009-04-28 | 2018-02-02 | Galecto Biotech Ab | Nuevos inhibidores de galactósidos de galectinas |
| DE102009026636B4 (de) | 2009-06-02 | 2011-04-14 | Pari Pharma Gmbh | Verfahren zum Verschweißen einer Membran mit einem Träger bei der Herstellung eines Membranverneblers |
| BR112013026313A8 (pt) * | 2011-04-12 | 2018-01-30 | Moerae Matrix Inc | composições e métodos para prevenir ou tratar doenças, condições ou processos caracterizados por proliferação anormal de fibroblastos e depósito de matriz extracelular |
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