MXPA06003379A - Antagonistas del receptor de trombina. - Google Patents
Antagonistas del receptor de trombina.Info
- Publication number
- MXPA06003379A MXPA06003379A MXPA06003379A MXPA06003379A MXPA06003379A MX PA06003379 A MXPA06003379 A MX PA06003379A MX PA06003379 A MXPA06003379 A MX PA06003379A MX PA06003379 A MXPA06003379 A MX PA06003379A MX PA06003379 A MXPA06003379 A MX PA06003379A
- Authority
- MX
- Mexico
- Prior art keywords
- mmol
- pharmaceutically acceptable
- compound
- solvate
- salt
- Prior art date
Links
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Classifications
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
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- Vascular Medicine (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| US10/671,216 US7488742B2 (en) | 2000-06-15 | 2003-09-25 | Thrombin receptor antagonists |
| PCT/US2004/031495 WO2005030712A2 (en) | 2003-09-25 | 2004-09-23 | Thrombin receptor antagonists |
Publications (1)
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| MXPA06003379A true MXPA06003379A (es) | 2006-06-08 |
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| MXPA06003379A MXPA06003379A (es) | 2003-09-25 | 2004-09-23 | Antagonistas del receptor de trombina. |
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| KR (1) | KR20060128848A (https=) |
| CN (1) | CN101128457A (https=) |
| AR (1) | AR045809A1 (https=) |
| AU (1) | AU2004276327B2 (https=) |
| BR (1) | BRPI0414592A (https=) |
| CA (1) | CA2540163C (https=) |
| CO (1) | CO5680428A2 (https=) |
| EC (1) | ECSP066455A (https=) |
| IL (1) | IL174538A0 (https=) |
| MX (1) | MXPA06003379A (https=) |
| MY (1) | MY143834A (https=) |
| NO (1) | NO20061797L (https=) |
| PE (1) | PE20050471A1 (https=) |
| RU (1) | RU2367660C9 (https=) |
| SG (1) | SG147466A1 (https=) |
| TW (1) | TWI331608B (https=) |
| WO (1) | WO2005030712A2 (https=) |
| ZA (1) | ZA200602448B (https=) |
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| US6346510B1 (en) | 1995-10-23 | 2002-02-12 | The Children's Medical Center Corporation | Therapeutic antiangiogenic endostatin compositions |
| US20040192753A1 (en) * | 2000-06-15 | 2004-09-30 | Samuel Chackalamannil | Methods of use of thrombin receptor antagonists |
| BRPI0309309B8 (pt) * | 2002-04-16 | 2021-05-25 | Merck Sharp & Dohme | antagonistas de receptor de trombina tricíclicos |
| ES2427166T3 (es) * | 2003-06-23 | 2013-10-29 | Ono Pharmaceutical Co., Ltd. | Compuesto heterocíclico tricíclico novedoso |
| CN1984905B (zh) * | 2004-05-28 | 2011-06-22 | 先灵公司 | 作为凝血酶受体拮抗剂的约束喜巴辛类似物 |
| US20060063930A1 (en) * | 2004-08-20 | 2006-03-23 | Agoston Gregory E | Compositions and methods comprising proteinase activated receptor antagonists |
| US8563511B2 (en) * | 2004-10-06 | 2013-10-22 | University Of Rochester | Treatment of pulmonary hypertension using an agent that inhibits a tissue factor pathway |
| US7488752B2 (en) * | 2004-10-08 | 2009-02-10 | Schering Corporation | Thrombin receptor antagonists |
| WO2006068164A1 (ja) * | 2004-12-22 | 2006-06-29 | Ono Pharmaceutical Co., Ltd. | 三環式化合物およびその用途 |
| CA2875768C (en) | 2005-01-14 | 2018-03-06 | George G. Wu | Process for the preparation of phosphonate compounds useful in the preparation of himbacine analogs |
| US7776889B2 (en) * | 2005-03-31 | 2010-08-17 | Schering Corporation | Spirocyclic thrombin receptor antagonists |
| WO2007075808A2 (en) * | 2005-12-20 | 2007-07-05 | Schering Corporation | Methods for preventing and/or treating a cell proliferative disorder |
| JP2009521458A (ja) * | 2005-12-22 | 2009-06-04 | シェーリング コーポレイション | トロンビン受容体アンタゴニストとしてのオキサゾロイソキノリン誘導体 |
| JP2009521472A (ja) * | 2005-12-22 | 2009-06-04 | シェーリング コーポレイション | 心肺手術の合併症の予防としてのトロンビンレセプターアンタゴニスト |
| AU2007243657A1 (en) * | 2006-03-29 | 2007-11-08 | Schering Corporation | Monocyclic and bicyclic himbacine derivatives useful as thrombin receptor antagonists |
| TW200812619A (en) * | 2006-04-06 | 2008-03-16 | Schering Corp | TRA combination therapies |
| US8003803B2 (en) * | 2006-04-13 | 2011-08-23 | Schering Corporation | Fused ring thrombin receptor antagonists |
| EP2032560B1 (en) * | 2006-06-29 | 2013-05-01 | Merck Sharp & Dohme Corp. | Substituted bicyclic and tricyclic thrombin receptor antagonists |
| TWI367112B (en) * | 2006-06-30 | 2012-07-01 | Schering Corp | Immediate-release tablet formulations of a thrombin receptor antagonist |
| DE102006036023A1 (de) * | 2006-08-02 | 2008-02-07 | Sanofi-Aventis | Imino-imidazo-pyridinderivate mit antithrombotischer Aktivität |
| TWI343262B (en) * | 2006-09-26 | 2011-06-11 | Schering Corp | Rapidly disintegrating lyophilized oral formulations of a thrombin receptor antagonist |
| EP2069326B1 (en) | 2006-10-04 | 2015-03-18 | Merck Sharp & Dohme Corp. | Bicyclic and tricyclic derivatives as thrombin receptor antagonists |
| EP2120879A2 (en) * | 2006-12-22 | 2009-11-25 | Schering Corporation | Disintegration promoters in solid dose wet granulation formulations |
| BRPI0809095A2 (pt) * | 2007-03-23 | 2014-09-09 | Schering Corp | Redução de eventos adversos após intervenção percutânea através de uso de um antagonista de receptor de trombina |
| SI2242740T1 (sl) | 2008-02-05 | 2013-03-29 | Sanofi | SF5-derivati kot PAR1 inhibitorji, njihova priprava in uporaba kot zdravila |
| RS52264B (sr) | 2008-02-05 | 2012-10-31 | Sanofi | Triazolopiridazini kao inhibitori par1, njihovo dobijanje i upotreba kao lekova |
| RU2494100C2 (ru) * | 2008-02-05 | 2013-09-27 | Санофи-Авентис | Соли триазолия в качестве ингибиторов par1, их получение и применение в качестве лекарственного средства |
| EP2438060B1 (en) | 2009-06-04 | 2013-10-02 | Merck Sharp & Dohme Corp. | Active metabolite of a thrombin receptor antagonist |
| JP2012529431A (ja) | 2009-06-08 | 2012-11-22 | メルク・シャープ・アンド・ドーム・コーポレーション | トロンビン受容体アンタゴニストおよびクロピドグレルの固定用量錠剤 |
| ES2532902T3 (es) | 2010-04-16 | 2015-04-01 | Sanofi | Piridil-vinil-pirroles tricíclicos como inhibidores de PAR1 |
| WO2011128420A1 (de) | 2010-04-16 | 2011-10-20 | Sanofi | Pyridyl-vinyl-pyrazolo-chinoline als par1-inhibitoren |
| WO2013134012A1 (en) | 2012-03-06 | 2013-09-12 | Merck Sharp & Dohme Corp. | Preparation and use of bicyclic himbacine derivatives as par-receptor antagonists |
| WO2015013083A1 (en) | 2013-07-22 | 2015-01-29 | Merck Sharp & Dohme Corp. | Co-crystal of the par-1 receptor antagonist vorapaxar and aspirin |
| WO2015026685A1 (en) * | 2013-08-22 | 2015-02-26 | Merck Sharp & Dohme Corp. | 7a-heterocycle substituted- 6, 6-difluoro bicyclic himbacine derivatives |
| EP3035928B1 (en) * | 2013-08-22 | 2023-10-18 | Merck Sharp & Dohme LLC | 3'-pyridyl substituted- 6,6-difluoro bicyclic himbacine derivatives |
| EP3035929B1 (en) * | 2013-08-22 | 2024-07-03 | Merck Sharp & Dohme LLC | 7a-amide substituted-6,6-difluoro bicyclic himbacine derivatives |
| WO2016114386A1 (ja) * | 2015-01-15 | 2016-07-21 | 国立研究開発法人国立精神・神経医療研究センター | 進行型免疫性脱髄疾患治療剤 |
| CN110407819B (zh) * | 2019-08-02 | 2020-06-26 | 牡丹江医学院 | 一种作为预防外科手术并发症的凝血酶受体拮抗剂 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000229961A (ja) * | 1998-12-11 | 2000-08-22 | Sagami Chem Res Center | ヒドロナフト［２，３−ｃ］フラン誘導体およびその製造方法 |
| US6063847A (en) * | 1997-11-25 | 2000-05-16 | Schering Corporation | Thrombin receptor antagonists |
| CZ298578B6 (cs) * | 1997-11-25 | 2007-11-14 | Schering Corporation | Heterocyklickou skupinou substituovaná tricyklická sloucenina a farmaceutický prostredek ji obsahující |
| AU6690001A (en) | 2000-06-15 | 2001-12-24 | Schering Corp | Thrombin receptor antagonists |
| US20040192753A1 (en) * | 2000-06-15 | 2004-09-30 | Samuel Chackalamannil | Methods of use of thrombin receptor antagonists |
| US7235567B2 (en) * | 2000-06-15 | 2007-06-26 | Schering Corporation | Crystalline polymorph of a bisulfate salt of a thrombin receptor antagonist |
| KR100960170B1 (ko) * | 2001-10-18 | 2010-05-26 | 쉐링 코포레이션 | 트롬빈 수용체 길항제로서의 힘바신 동족체 |
| BRPI0309309B8 (pt) * | 2002-04-16 | 2021-05-25 | Merck Sharp & Dohme | antagonistas de receptor de trombina tricíclicos |
| CN1984905B (zh) * | 2004-05-28 | 2011-06-22 | 先灵公司 | 作为凝血酶受体拮抗剂的约束喜巴辛类似物 |
| JP2008526254A (ja) * | 2005-01-14 | 2008-07-24 | シェーリング コーポレイション | ヒンバシン類似物のキラルプロパルギルアルコールおよびエステル中間体の調製 |
| CA2875768C (en) * | 2005-01-14 | 2018-03-06 | George G. Wu | Process for the preparation of phosphonate compounds useful in the preparation of himbacine analogs |
| US7541471B2 (en) * | 2005-01-14 | 2009-06-02 | Schering Corporation | Synthesis of himbacine analogs |
| WO2006076452A2 (en) * | 2005-01-14 | 2006-07-20 | Schering Corporation | An exo-selective synthesis of himbacine analogs |
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2003
- 2003-09-25 US US10/671,216 patent/US7488742B2/en not_active Expired - Lifetime
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2004
- 2004-09-23 CN CNA2004800278261A patent/CN101128457A/zh active Pending
- 2004-09-23 SG SG200807889-1A patent/SG147466A1/en unknown
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- 2004-09-23 EP EP04789042.1A patent/EP1663965B1/en not_active Expired - Lifetime
- 2004-09-23 PE PE2004000927A patent/PE20050471A1/es not_active Application Discontinuation
- 2004-09-23 JP JP2006528258A patent/JP4694490B2/ja not_active Expired - Fee Related
- 2004-09-23 KR KR1020067005753A patent/KR20060128848A/ko not_active Ceased
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| US20090069383A1 (en) | 2009-03-12 |
| CN101128457A (zh) | 2008-02-20 |
| EP1663965B1 (en) | 2014-04-09 |
| US20040152736A1 (en) | 2004-08-05 |
| MY143834A (en) | 2011-07-15 |
| WO2005030712A8 (en) | 2007-12-21 |
| CA2540163C (en) | 2012-06-05 |
| CO5680428A2 (es) | 2006-09-29 |
| WO2005030712A2 (en) | 2005-04-07 |
| RU2367660C9 (ru) | 2010-08-10 |
| ZA200602448B (en) | 2007-09-26 |
| AU2004276327B2 (en) | 2010-10-07 |
| CA2540163A1 (en) | 2005-04-07 |
| JP2007523051A (ja) | 2007-08-16 |
| JP4694490B2 (ja) | 2011-06-08 |
| TW200524914A (en) | 2005-08-01 |
| TWI331608B (en) | 2010-10-11 |
| IL174538A0 (en) | 2006-08-01 |
| RU2367660C2 (ru) | 2009-09-20 |
| US20090076088A1 (en) | 2009-03-19 |
| BRPI0414592A (pt) | 2006-11-07 |
| US7488742B2 (en) | 2009-02-10 |
| KR20060128848A (ko) | 2006-12-14 |
| NO20061797L (no) | 2006-05-19 |
| SG147466A1 (en) | 2008-11-28 |
| EP1663965A2 (en) | 2006-06-07 |
| AU2004276327A1 (en) | 2005-04-07 |
| WO2005030712A3 (en) | 2007-09-20 |
| RU2006113638A (ru) | 2007-11-10 |
| PE20050471A1 (es) | 2005-08-24 |
| AR045809A1 (es) | 2005-11-16 |
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