TW201443054A - 化合物 - Google Patents
化合物 Download PDFInfo
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- TW201443054A TW201443054A TW103102388A TW103102388A TW201443054A TW 201443054 A TW201443054 A TW 201443054A TW 103102388 A TW103102388 A TW 103102388A TW 103102388 A TW103102388 A TW 103102388A TW 201443054 A TW201443054 A TW 201443054A
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- oxy
- prepared
- dihydroimidazo
- esi
- compound
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Classifications
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Epidemiology (AREA)
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| WO2016012916A1 (en) * | 2014-07-22 | 2016-01-28 | Glaxosmithkline Intellectual Property Development Limited | 1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2 |
| JP6625604B2 (ja) * | 2014-07-22 | 2019-12-25 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | 化合物 |
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| CN112574221B (zh) * | 2019-09-30 | 2022-03-04 | 上海纽思克生物科技有限公司 | 四环嘧啶酮类化合物、其制备方法、其组合物和用途 |
| IL292668A (en) * | 2019-11-09 | 2022-07-01 | Shanghai Simr Biotechnology Co Ltd | A tricyclic derivative of dihydroimidazopyrimidone, its preparation method, pharmaceutical preparation and its use |
| CN111533699B (zh) * | 2020-05-27 | 2023-12-01 | 龙曦宁（上海）医药科技有限公司 | 一种2-（三氟甲基）嘧啶-5-醇的合成方法 |
| CN113861220B (zh) * | 2020-06-30 | 2023-06-16 | 上海纽思克生物科技有限公司 | 三环嘧啶酮类化合物、其制备方法、其组合物和用途 |
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| CN115304620A (zh) | 2021-05-07 | 2022-11-08 | 上海赛默罗生物科技有限公司 | 嘧啶酮衍生物、其制备方法、药物组合物和用途 |
| CN114057740B (zh) * | 2021-12-15 | 2024-04-02 | 上海赛默罗生物科技有限公司 | 螺环嘧啶酮衍生物、其制备方法、药物组合物和用途 |
| EP4565587A1 (en) * | 2022-08-04 | 2025-06-11 | 4B Technologies (Beijing) Co., Limited | Dihydroimidazo-pyrimidinone compounds as lp-pla2 inhibitors and use thereof |
| CN116925023B (zh) * | 2023-07-18 | 2025-11-21 | 江苏桐孚高新材料有限公司 | 2-全氟烷基-4h-吡喃-4-酮衍生物的改进合成方法 |
Family Cites Families (48)
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| CH690264A5 (fr) | 1995-06-30 | 2000-06-30 | Symphar Sa | Dérivés aminophosphonates substitués, leur procédé de préparation et leur utilisation pour la préparation de compositions pharmaceutiques. |
| CZ422197A3 (cs) | 1995-07-01 | 1998-06-17 | Smithkline Beecham Plc | Azetidinonové deriváty, způsob jejich přípravy, meziprodukty tohoto postupu, farmaceutický prostředek obsahující tyto sloučeniny a použití těchto sloučenin jako léčiv |
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| JP3757703B2 (ja) | 1999-09-22 | 2006-03-22 | 凸版印刷株式会社 | 再封可能な開口維持部材付パウチ |
| ES2330552T3 (es) | 2000-02-16 | 2009-12-11 | Smithkline Beecham Plc | Derivados de pirimidin-5-ona como inhibidores de ldl-pla2. |
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| WO2005003118A1 (de) | 2003-07-02 | 2005-01-13 | Bayer Healthcare Ag | Amid-substituierte 1,2,4-triazin-5 (2h)-one zur behandlung von chronisch inflammatorischen krankheiten |
| DE102004061009A1 (de) | 2004-12-18 | 2006-06-22 | Bayer Healthcare Ag | Substituierte 1,2,4-Triazin-5(2H)-one |
| DE102004061008A1 (de) | 2004-12-18 | 2006-06-22 | Bayer Healthcare Ag | 3-Arylalkyl- und 3-Heteroarylalkyl-substituierte 1,2,4-Triazin-5(2H)-one |
| EP2083625A4 (en) * | 2006-10-13 | 2011-10-19 | Glaxo Group Ltd | BICYCLIC HETOROAROMATIC COMPOUNDS |
| US7705005B2 (en) | 2006-10-13 | 2010-04-27 | Glaxo Group Limited | Bicyclic heteroaromatic compounds |
| US20080090852A1 (en) | 2006-10-13 | 2008-04-17 | Colin Andrew Leach | Bicyclic Heteroaromatic Compounds |
| US20080090851A1 (en) | 2006-10-13 | 2008-04-17 | Colin Andrew Leach | Bicyclic Heteroaromatic Compounds |
| WO2008104077A1 (en) | 2007-02-28 | 2008-09-04 | Methylgene Inc. | Small molecule inhibitors of protein arginine methyltransferases (prmts) |
| BRPI0810336A2 (pt) | 2007-05-11 | 2019-03-19 | The Trustees Of The University Of Pennsylvania | "método para tratar e/ou prevenir úlceras de pele em um indivíduo" |
| US20080279846A1 (en) | 2007-05-11 | 2008-11-13 | Thomas Jefferson University | Methods of treatment and prevention of neurodegenerative diseases and disorders |
| US8962633B2 (en) | 2007-05-11 | 2015-02-24 | Thomas Jefferson University | Methods of treatment and prevention of metabolic bone diseases and disorders |
| JP2011088847A (ja) * | 2009-10-21 | 2011-05-06 | Takeda Chem Ind Ltd | 三環性化合物およびその用途 |
| EP2619203A4 (en) * | 2010-09-20 | 2014-04-16 | Glaxo Group Ltd | TRICYCLIC COMPOUNDS, PROCESS FOR THEIR PREPARATION AND APPLICATIONS THEREOF |
| EP2649050A4 (en) * | 2010-12-06 | 2014-04-23 | Glaxo Group Ltd | LINKS |
| EP2651403B1 (en) | 2010-12-17 | 2020-12-02 | Glaxo Group Limited | Use of lp-pla2 inhibitors in the treatment and prevention of eye diseases |
| JP2014521611A (ja) * | 2011-07-27 | 2014-08-28 | グラクソ グループ リミテッド | Ｌｐ−ＰＬＡ２阻害剤としての２，３−ジヒドロイミダゾ［１，２−ｃ］ピリミジン−５（１Ｈ）−オン化合物の使用 |
| CN103827116B (zh) | 2011-07-27 | 2016-08-31 | 葛兰素集团有限公司 | 用作LP-PLA2抑制剂的2,3-二氢咪唑并[1,2-c]嘧啶-5(1H)-酮化合物 |
| TW201443054A (zh) | 2013-01-25 | 2014-11-16 | Glaxosmithkline Ip Dev Ltd | 化合物 |
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2014
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- 2014-01-23 AU AU2014209949A patent/AU2014209949B2/en not_active Ceased
- 2014-01-23 ES ES14701355.1T patent/ES2642762T3/es active Active
- 2014-01-23 UY UY0001035276A patent/UY35276A/es not_active Application Discontinuation
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- 2014-01-23 HK HK16104389.3A patent/HK1216425A1/zh unknown
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- 2014-01-23 SG SG11201505520WA patent/SG11201505520WA/en unknown
- 2014-01-23 MA MA38284A patent/MA38284B1/fr unknown
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- 2014-01-23 PE PE2015001537A patent/PE20151251A1/es not_active Application Discontinuation
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2015
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Also Published As
| Publication number | Publication date |
|---|---|
| EP2948452A1 (en) | 2015-12-02 |
| PH12015501586A1 (en) | 2015-10-05 |
| CN105008368B (zh) | 2017-02-01 |
| EP2948452B1 (en) | 2017-08-09 |
| US9708330B2 (en) | 2017-07-18 |
| JP2016505058A (ja) | 2016-02-18 |
| US20150361082A1 (en) | 2015-12-17 |
| AU2014209949B2 (en) | 2016-09-08 |
| HK1216425A1 (zh) | 2016-11-11 |
| KR20150108897A (ko) | 2015-09-30 |
| CN105008368A (zh) | 2015-10-28 |
| JP6306053B2 (ja) | 2018-04-04 |
| ES2642762T3 (es) | 2017-11-20 |
| UY35276A (es) | 2014-08-29 |
| MX2015009633A (es) | 2015-11-30 |
| CA2899091A1 (en) | 2014-07-31 |
| EA201591379A1 (ru) | 2016-01-29 |
| BR112015017759B1 (pt) | 2022-05-24 |
| SG11201505520WA (en) | 2015-08-28 |
| IL240046A0 (en) | 2015-08-31 |
| CL2015002060A1 (es) | 2015-11-27 |
| MA38284A1 (fr) | 2017-12-29 |
| PE20151251A1 (es) | 2015-09-10 |
| CR20150390A (es) | 2015-10-19 |
| MA38284B1 (fr) | 2018-05-31 |
| EA025885B1 (ru) | 2017-02-28 |
| ZA201505025B (en) | 2017-08-30 |
| AU2014209949A1 (en) | 2015-07-30 |
| WO2014114694A1 (en) | 2014-07-31 |
| BR112015017759A2 (pt) | 2017-07-11 |
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