EA019711B1 - ПРОИЗВОДНЫЕ 1-БЕНЗИЛ-3-ГИДРОКСИМЕТИЛИНДАЗОЛА, СОДЕРЖАЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И ИХ ПРИМЕНЕНИЕ ПРИ ЛЕЧЕНИИ ЗАБОЛЕВАНИЙ, ОБУСЛОВЛЕННЫХ ЭКСПРЕССИЕЙ МСР-1, СХ3CR1 ИЛИ р40 - Google Patents
ПРОИЗВОДНЫЕ 1-БЕНЗИЛ-3-ГИДРОКСИМЕТИЛИНДАЗОЛА, СОДЕРЖАЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И ИХ ПРИМЕНЕНИЕ ПРИ ЛЕЧЕНИИ ЗАБОЛЕВАНИЙ, ОБУСЛОВЛЕННЫХ ЭКСПРЕССИЕЙ МСР-1, СХ3CR1 ИЛИ р40 Download PDFInfo
- Publication number
- EA019711B1 EA019711B1 EA201071040A EA201071040A EA019711B1 EA 019711 B1 EA019711 B1 EA 019711B1 EA 201071040 A EA201071040 A EA 201071040A EA 201071040 A EA201071040 A EA 201071040A EA 019711 B1 EA019711 B1 EA 019711B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- hydrogen atom
- carbon atoms
- group
- indazol
- methoxy
- Prior art date
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| EP08425139 | 2008-03-07 | ||
| PCT/EP2009/052590 WO2009109618A2 (en) | 2008-03-07 | 2009-03-05 | Novel 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of mcp-1, cx3cr1 and p40 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201071040A1 EA201071040A1 (ru) | 2011-02-28 |
| EA019711B1 true EA019711B1 (ru) | 2014-05-30 |
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| EA201071040A EA019711B1 (ru) | 2008-03-07 | 2009-03-05 | ПРОИЗВОДНЫЕ 1-БЕНЗИЛ-3-ГИДРОКСИМЕТИЛИНДАЗОЛА, СОДЕРЖАЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И ИХ ПРИМЕНЕНИЕ ПРИ ЛЕЧЕНИИ ЗАБОЛЕВАНИЙ, ОБУСЛОВЛЕННЫХ ЭКСПРЕССИЕЙ МСР-1, СХ3CR1 ИЛИ р40 |
| EA201071038A EA018241B1 (ru) | 2008-03-07 | 2009-03-05 | ПРОИЗВОДНЫЕ 1-БЕНЗИЛ-3-ГИДРОКСИМЕТИЛИНДАЗОЛА И ИХ ПРИМЕНЕНИЕ ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ, ОСНОВАННЫХ НА ЭКСПРЕССИИ MCP-1, CX3CR1 И p40 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
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| EA201071038A EA018241B1 (ru) | 2008-03-07 | 2009-03-05 | ПРОИЗВОДНЫЕ 1-БЕНЗИЛ-3-ГИДРОКСИМЕТИЛИНДАЗОЛА И ИХ ПРИМЕНЕНИЕ ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ, ОСНОВАННЫХ НА ЭКСПРЕССИИ MCP-1, CX3CR1 И p40 |
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| SI (2) | SI2254870T1 (enExample) |
| UA (2) | UA105170C2 (enExample) |
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Families Citing this family (21)
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| US8314099B2 (en) | 2008-03-07 | 2012-11-20 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of MCP-1 and CX3CR1 |
| EP2262778B8 (en) | 2008-03-07 | 2020-01-01 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.p.A. | 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of mcp-1, cx3cr1 and p40 |
| PL2254870T3 (pl) * | 2008-03-07 | 2016-07-29 | Acraf | Pochodne 1-benzylo-3-hydroksymetyloindazolu i ich zastosowanie w leczeniu chorób opartych na ekspresji MCP-1, CX3CR1 |
| PL2462119T3 (pl) * | 2009-08-03 | 2014-10-31 | Acraf | Sposób wytwarzania 1-benzylo-3-hydroksymetylo-1H-indazolu i jego pochodnych oraz potrzebnych magnezowych związków pośrednich |
| UA108742C2 (uk) * | 2009-09-23 | 2015-06-10 | Фармацевтична композиція для лікування запальних захворювань, опосередкованих mcp-1 | |
| US8999292B2 (en) | 2012-05-01 | 2015-04-07 | Translatum Medicus Inc. | Methods for treating and diagnosing blinding eye diseases |
| EP2844250B1 (en) * | 2012-05-01 | 2017-11-08 | Translatum Medicus Inc. | Methods for treating and diagnosing blinding eye diseases |
| EP2882715B1 (en) | 2012-05-18 | 2016-11-09 | Sanofi | Pyrazole derivatives and their use as lpar5 antagonists |
| JP2015521183A (ja) | 2012-05-18 | 2015-07-27 | サノフイ | ピリジン誘導体および病理学的血栓形成に関連する状態の治療へのその使用 |
| AR093422A1 (es) | 2012-11-09 | 2015-06-03 | Colgate Palmolive Co | Copolimeros de bloque para proteccion del esmalte dental |
| HUE049518T2 (hu) * | 2014-05-15 | 2020-09-28 | Translatum Medicus Inc | Készítmények és eljárások a szem megbetegedéseinek kezelésére és diagnosztizálására |
| EP3942934A1 (en) * | 2015-06-12 | 2022-01-26 | Vettore, LLC | Mct4 inhibitors for treating disease |
| US20180221339A1 (en) * | 2015-06-16 | 2018-08-09 | Translatum Medicus, Inc. | Compositions and methods for treating and diagnosing ocular disorders |
| MX391489B (es) * | 2016-12-12 | 2025-03-21 | Vettore Llc | Inhibidores heterociclicos de mct4. |
| GB201811169D0 (en) | 2018-07-06 | 2018-08-29 | Kancera Ab | New compounds |
| JP6612004B1 (ja) * | 2018-07-31 | 2019-11-27 | 株式会社親広産業 | グルコース消費促進剤および解糖系促進剤 |
| WO2020026471A1 (ja) * | 2018-07-31 | 2020-02-06 | 株式会社親広産業 | グルコース消費促進剤および解糖系促進剤 |
| EP3990433A4 (en) | 2019-06-25 | 2023-07-26 | Translatum Medicus Inc. | METHODS FOR THE MANUFACTURE OF 2-((1-BENZYL-1H-INDAZOL-3-YL)METHOXY)-2-METHYLPROPANOIC ACID AND ITS DERIVATIVES |
| CN113929627A (zh) * | 2021-10-19 | 2022-01-14 | 吕梁学院 | 一种宾达利的合成方法 |
| WO2024108386A1 (zh) * | 2022-11-22 | 2024-05-30 | 中国科学院深圳先进技术研究院 | 抗mcp1中和抗体在制备治疗神经退行性疾病引起的系统性炎症药物中的应用 |
| EP4662203A1 (en) * | 2023-02-10 | 2025-12-17 | Translatum Medicus Inc. | Bindarit conjugates, compositions and methods for treating ocular diseases or disorders |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0382276A2 (en) * | 1989-02-07 | 1990-08-16 | AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.p.A. | Ethers of 1-benzyl-3-hydroxymethyl-indazole with aliphatic 2-hydroxyacids |
| EP0510748A1 (en) * | 1991-04-22 | 1992-10-28 | ANGELINI RICERCHE S.p.A. SOCIETA' CONSORTILE | Use of a methoxy alkanoic acid of indazole for the manufacture of a medicament for the treatment of autoimmune diseases |
| WO1999004770A2 (en) * | 1997-07-28 | 1999-02-04 | AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.P.A. (Trading also as ACRAF S.P.A.) | A pharmaceutical composition active in reducing production of mcp-1 protein |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US416359A (en) * | 1889-12-03 | Sash-fastener | ||
| US364371A (en) * | 1887-06-07 | peice | ||
| EP1185528A4 (en) | 1999-06-17 | 2003-03-26 | Shionogi Biores Corp | INHIBITORS OF IL-12 PRODUCTION |
| EP1199074A1 (en) | 2000-09-15 | 2002-04-24 | Warner-Lambert Company | Pharmaceutical composition for preventing or treating a disease associated with an excess of il-12 production |
| EP1188438A1 (en) | 2000-09-15 | 2002-03-20 | Warner-Lambert Company | Pharmaceutical composition for preventing or treating a disease associated with an excess of Il-12 production |
| JP4234439B2 (ja) | 2001-03-15 | 2009-03-04 | 生化学工業株式会社 | Ｉｌ−１２発現調節剤 |
| MXPA04005181A (es) | 2001-11-30 | 2005-06-17 | Synta Pharmaceuticals Corp | Compuestos de pirimidina. |
| MXPA06003792A (es) | 2003-10-07 | 2006-06-14 | Astrazeneca Ab | Nuevas 4-amino-tiazolo[4,5-d]-pirimidinas 2-sustituidas, utiles como antagonistas del receptor de quimiocina, especialmente cx3cr1. |
| JP4979388B2 (ja) * | 2004-10-29 | 2012-07-18 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 炎症性疾患治療剤 |
| TW200628159A (en) | 2004-11-10 | 2006-08-16 | Synta Pharmaceuticals Corp | IL-12 modulatory compounds |
| CA2587590A1 (en) | 2004-11-19 | 2006-06-08 | Synta Pharmaceuticals Corp. | Pyrimidine compounds and uses thereof |
| UA90707C2 (en) | 2005-04-06 | 2010-05-25 | Астразенека Аб | Novel 5-substituted 7-amino-[1,3]thiazolo[4,5-d]pyrimidine derivatives |
| AR053347A1 (es) | 2005-04-06 | 2007-05-02 | Astrazeneca Ab | Derivados de [1,3]tiazolo[4,5-d]pirimidin-2(3h)-ona 5,7-sustituidos |
| US8314099B2 (en) * | 2008-03-07 | 2012-11-20 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of MCP-1 and CX3CR1 |
| PL2254870T3 (pl) * | 2008-03-07 | 2016-07-29 | Acraf | Pochodne 1-benzylo-3-hydroksymetyloindazolu i ich zastosowanie w leczeniu chorób opartych na ekspresji MCP-1, CX3CR1 |
| EP2262778B8 (en) * | 2008-03-07 | 2020-01-01 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.p.A. | 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of mcp-1, cx3cr1 and p40 |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0382276A2 (en) * | 1989-02-07 | 1990-08-16 | AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.p.A. | Ethers of 1-benzyl-3-hydroxymethyl-indazole with aliphatic 2-hydroxyacids |
| EP0510748A1 (en) * | 1991-04-22 | 1992-10-28 | ANGELINI RICERCHE S.p.A. SOCIETA' CONSORTILE | Use of a methoxy alkanoic acid of indazole for the manufacture of a medicament for the treatment of autoimmune diseases |
| WO1999004770A2 (en) * | 1997-07-28 | 1999-02-04 | AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.P.A. (Trading also as ACRAF S.P.A.) | A pharmaceutical composition active in reducing production of mcp-1 protein |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
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