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 | |
| CA2794066A CA2794066C (en) | 2012-10-31 | 2012-10-31 | Galactoside inhibitor of galectins |
| CA2794066 | 2012-10-31 | ||
| US61/720,641 | 2012-10-31 | ||
| CA2795753A CA2795753A1 (en) | 2012-10-31 | 2012-11-15 | Novel galactoside inhibitor of galectins |
| CA2795793 | 2012-11-15 | ||
| US13/832,672 US9243021B2 (en) | 2012-10-31 | 2013-03-15 | Galactoside inhibitor of galectins |
| US13/832,672 | 2013-03-15 | ||
| CA2884802A CA2884802A1 (en) | 2012-10-31 | 2013-10-30 | Galactoside inhibitor of galectin-3 and its use for treating pulmonary fibrosis |
| PCT/EP2013/072691 WO2014067986A1 (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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| Country | Link |
|---|---|
| EP (2) | EP3278805A1 (OSRAM) |
| JP (1) | JP2015535233A (OSRAM) |
| CN (1) | CN104755088A (OSRAM) |
| CA (1) | CA2884802A1 (OSRAM) |
| ES (1) | ES2817888T3 (OSRAM) |
| IN (1) | IN2015DN02573A (OSRAM) |
| WO (1) | WO2014067986A1 (OSRAM) |
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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 |
| EP3166956B1 (en) * | 2014-07-09 | 2020-03-18 | Galecto Biotech AB | Novel hybrid galactoside inhibitor of galectins |
| ES2776255T3 (es) | 2015-01-16 | 2020-07-29 | Galecto Biotech Ab | Novedoso inhibidor de galactósido de galectinas |
| CN113621005B (zh) | 2015-01-30 | 2025-07-04 | 格莱克特生物技术公司 | 半乳糖凝集素的α-D-半乳糖苷抑制剂 |
| EP3294293B1 (en) | 2015-05-12 | 2020-11-18 | 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 |
| US10369136B2 (en) | 2015-12-18 | 2019-08-06 | Galecto Biotech Ab | Polymorphic forms and process |
| KR102346913B1 (ko) * | 2016-03-04 | 2022-01-04 | 갈랙틴 사이언시즈, 엘엘씨 | 갈렉틴과 관련된 질환의 예방 및 치료를 위한 셀레노갈락토시드 화합물 및 이의 용도 |
| WO2018011093A1 (en) | 2016-07-12 | 2018-01-18 | Galecto Biotech Ab | Alpha-d-galactoside inhibitors of galectins |
| CN109563119A (zh) * | 2016-07-12 | 2019-04-02 | 格莱克特生物技术公司 | 半乳糖凝集素的α-D-半乳糖苷抑制剂 |
| CA3062648A1 (en) * | 2017-05-12 | 2018-11-15 | Galectin Sciences, Llc | Compounds for the prevention and treatment of diseases and the use thereof |
| WO2019067702A1 (en) | 2017-09-27 | 2019-04-04 | Bristol-Myers Squibb Company | INHIBITORS WITH SMALL MOLECULES OF GALECTIN-3 |
| WO2019075045A1 (en) | 2017-10-11 | 2019-04-18 | Bristol-Myers Squibb Company | INHIBITORS WITH SMALL MOLECULES OF GALECTIN-3 |
| CA3085356A1 (en) | 2017-12-29 | 2019-07-04 | Glycomimetics, Inc. | Heterobifunctional inhibitors of e-selectin and galectin-3 |
| WO2019137971A1 (en) | 2018-01-10 | 2019-07-18 | Galecto Biotech Ab | Novel galactoside inhibitor of galectins |
| WO2019222483A1 (en) | 2018-05-17 | 2019-11-21 | Board Of Regents, The University Of Texas System | Treatment of idiopathic pulmonary fibrosis with glycogen synthase kinase 3 form beta inhibitors |
| JP7190513B2 (ja) * | 2018-06-15 | 2022-12-15 | ブリストル－マイヤーズ スクイブ カンパニー | ガレクチン－３抑制剤を模したテトラヒドロピラン系チオ二糖類 |
| 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 |
| CA3116515A1 (en) | 2018-11-21 | 2020-05-28 | Galecto Biotech Ab | Alpha-d-galactoside inhibitors of galectins |
| CN113166122A (zh) | 2018-12-06 | 2021-07-23 | 百时美施贵宝公司 | 半乳糖凝集素-3的小分子抑制剂 |
| BR112021012482A2 (pt) | 2018-12-27 | 2021-09-08 | Glycomimetics, Inc. | C-glicosídeos inibidores de galectina-3 |
| US11845771B2 (en) | 2018-12-27 | 2023-12-19 | Glycomimetics, Inc. | Heterobifunctional inhibitors of E-selectin and galectin-3 |
| WO2020198266A1 (en) | 2019-03-26 | 2020-10-01 | Bristol-Myers Squibb Company | Small molecule inhibitors of galectin-3 |
| KR102890853B1 (ko) | 2019-04-10 | 2025-11-24 | 브리스톨-마이어스 스큅 컴퍼니 | 갈렉틴-3의 소분자 억제제 |
| WO2020248068A1 (en) | 2019-06-14 | 2020-12-17 | UNIVERSITé LAVAL | Synthesis of 3-azido-3-deoxy-d-galactopyranose |
| WO2020260351A1 (en) | 2019-06-24 | 2020-12-30 | Galecto Biotech Ab | Large scale process of 3,3'-dideoxy-3,3'-bis-[4-(3-fluorophenyl)-1h-1,2,3-triazol-1-yl]-1,1'-sulfanediyl-di-beta-d-galactopyranoside |
| US12441754B2 (en) | 2019-07-03 | 2025-10-14 | Galecto Biotech Ab | Galactoside inhibitor of galectins |
| EP3993872A1 (en) | 2019-07-03 | 2022-05-11 | Galecto Biotech AB | Novel galactoside inhibitor of galectins |
| CN114450282A (zh) | 2019-07-05 | 2022-05-06 | 格莱克特生物技术公司 | 半乳糖凝集素的新型半乳糖苷抑制剂 |
| CN114206892A (zh) | 2019-08-09 | 2022-03-18 | 爱杜西亚药品有限公司 | (2-乙酰氨基)硫代-β-D-吡喃半乳糖苷衍生物 |
| JP7612662B2 (ja) | 2019-08-09 | 2025-01-14 | イドルシア・ファーマシューティカルズ・リミテッド | （ヘテロ）アリール－メチル－チオ－ベータ－ｄ－ガラクトピラノシド誘導体 |
| UA128909C2 (uk) | 2019-08-15 | 2024-11-20 | Ідорсія Фармасьютікалз Лтд | 2-гідроксициклоалкан-1-карбамоїльні похідні |
| WO2021038068A1 (en) | 2019-08-29 | 2021-03-04 | Idorsia Pharmaceuticals Ltd | Alpha-d-galactopyranoside derivatives |
| US20230038373A1 (en) | 2019-12-18 | 2023-02-09 | Glykos Biomedical Oy | Stabile conjugate |
| US20230107479A1 (en) * | 2020-03-23 | 2023-04-06 | G3 Pharmaceuticals, Inc. | Methods and compositions for preventing and treating fibrosis resulting from a coronavirus infection |
| CA3173316A1 (en) * | 2020-03-31 | 2021-10-07 | Galecto Biotech Ab | Large scale process for preparing 1,2,4, 6-tetra-0-acetyl-3-azid0-3-de0xy-d-galact0pyran0side |
| EP4146646A1 (en) | 2020-05-05 | 2023-03-15 | Bristol-Myers Squibb Company | Small molecule inhibitors of galectin-3 |
| EP4149939A1 (en) | 2020-05-11 | 2023-03-22 | Bristol-Myers Squibb Company | Small molecule inhibitors of galectin-3 |
| CN115768768A (zh) | 2020-05-28 | 2023-03-07 | 百时美施贵宝公司 | 半乳凝素-3抑制剂 |
| TWI890869B (zh) | 2020-10-06 | 2025-07-21 | 瑞士商愛杜西亞製藥有限公司 | α-D-吡喃半乳糖苷之螺衍生物 |
| WO2022090544A1 (en) | 2020-11-02 | 2022-05-05 | Idorsia Pharmaceuticals Ltd | Galectin-3 inhibiting 2-hydroxycycloalkane-1 -carbamoyl derivatives |
| EP4291556B1 (en) | 2021-02-09 | 2025-04-23 | Idorsia Pharmaceuticals Ltd | Hydroxyheterocycloalkane-carbamoyl derivatives |
| IL305581A (en) | 2021-03-03 | 2023-10-01 | Idorsia Pharmaceuticals Ltd | Triazolyl-methyl-converted alpha-D-galactopyranoside histories |
| WO2025111704A1 (en) * | 2023-12-01 | 2025-06-05 | UNIVERSITé LAVAL | Selective inhibitors of galectin-3 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP0170715B1 (de) | 1984-08-09 | 1988-04-13 | Inge Brugger | Zerstäubervorrichtung |
| 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 |
| ES2141108T3 (es) | 1991-07-02 | 2000-03-16 | Inhale Inc | Metodo y dispositivo para proporcionar medicamentos en aerosol. |
| WO1997025086A2 (en) | 1996-01-03 | 1997-07-17 | 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 |
| EP1304130B1 (de) | 2001-10-18 | 2004-06-23 | PARI GmbH Spezialisten für effektive Inhalation | Inhalationstherapievorrichtung |
| WO2003045383A1 (en) * | 2001-11-26 | 2003-06-05 | Arachnova Therapeutics Ltd. | Use of ppar activators for the treatment of pulmonary fibrosis |
| EP1386672B1 (en) | 2002-08-02 | 2010-04-07 | PARI Pharma GmbH | Fluid droplet production apparatus |
| 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 |
| EP2424873B1 (en) | 2009-04-28 | 2017-11-15 | Galecto Biotech AB | Novel galactoside inhibitors of galectins |
| DE102009026636B4 (de) | 2009-06-02 | 2011-04-14 | Pari Pharma Gmbh | Verfahren zum Verschweißen einer Membran mit einem Träger bei der Herstellung eines Membranverneblers |
| CN108014340A (zh) * | 2011-04-12 | 2018-05-11 | 莫伊莱麦屈克斯公司 | 用于预防或治疗以成纤维细胞异常增殖及细胞外基质沉积为特征的疾病的组合物和方法 |
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| EP2914269A1 (en) | 2015-09-09 |
| ES2817888T3 (es) | 2021-04-08 |
| IN2015DN02573A (OSRAM) | 2015-09-11 |
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