KR20140023332A - 티에노〔２，３ｄ〕피리미딘 유도체 및 부정맥을 치료하기 위한 이의 용도 - Google Patents
티에노〔２，３ｄ〕피리미딘 유도체 및 부정맥을 치료하기 위한 이의 용도 Download PDFInfo
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- KR20140023332A KR20140023332A KR1020137028742A KR20137028742A KR20140023332A KR 20140023332 A KR20140023332 A KR 20140023332A KR 1020137028742 A KR1020137028742 A KR 1020137028742A KR 20137028742 A KR20137028742 A KR 20137028742A KR 20140023332 A KR20140023332 A KR 20140023332A
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1105659.5A GB201105659D0 (en) | 2011-04-01 | 2011-04-01 | Compounds |
| GB1105659.5 | 2011-04-01 | ||
| PCT/GB2012/050710 WO2012131379A1 (en) | 2011-04-01 | 2012-03-29 | Thieno [2, 3 -d] pyrimidine derivatives and their use to treat arrhythmia |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20140023332A true KR20140023332A (ko) | 2014-02-26 |
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| KR1020137028742A Ceased KR20140023332A (ko) | 2011-04-01 | 2012-03-29 | 티에노〔２，３ｄ〕피리미딘 유도체 및 부정맥을 치료하기 위한 이의 용도 |
Country Status (42)
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150307532A1 (en) * | 2012-11-20 | 2015-10-29 | The Royal Institution For The Advancement Of Learning/Mcgill University | Thienopyrimidine inhibitors of farnesyl and/or geranylgeranyl pyrophosphate synthase |
| WO2017112777A1 (en) | 2015-12-22 | 2017-06-29 | SHY Therapeutics LLC | Compounds for the treatment of cancer and inflammatory disease |
| CN106727587A (zh) * | 2016-11-28 | 2017-05-31 | 李娜 | 一种治疗心律失常的药物组合物 |
| KR102736865B1 (ko) | 2017-06-21 | 2024-12-03 | 샤이 테라퓨틱스 엘엘씨 | 암, 염증성 질환, 신경발달질환 및 섬유증 질환의 치료를 위하여 Ras 수퍼패밀리와 상호작용하는 화합물 |
| JP7407461B2 (ja) | 2018-12-19 | 2024-01-04 | シャイ・セラピューティクス・エルエルシー | がん、炎症性疾患、ｒａｓ病、及び線維性疾患の処置のためのｒａｓスーパーファミリーと相互作用する化合物 |
Family Cites Families (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH317906A (de) | 1953-09-16 | 1956-12-15 | Sandoz Ag | Verfahren zur Herstellung von 1-Amino-4-oxyanthrachinonsulfonsäuren |
| AU521790B2 (en) | 1977-05-23 | 1982-04-29 | Ici Australia Limited | Process for eradication of ticks |
| ZA782648B (en) | 1977-05-23 | 1979-06-27 | Ici Australia Ltd | The prevention,control or eradication of infestations of ixodid ticks |
| DD226893A1 (de) | 1981-12-15 | 1985-09-04 | Ralf Boehm | Verfahren zur herstellung von arylaminosubstituierten thieno 2,3-d pyrimidinen |
| IL112566A (en) | 1994-02-10 | 2000-10-31 | Wyeth John & Brother Ltd | Substituted quinolinones and pharmaceutical compositions containing them |
| IL112567A (en) | 1994-02-10 | 2000-02-29 | Wyeth John & Brother Ltd | Substituted quinolines their preparation and pharmaceutical compositions containing them |
| IL112569A (en) | 1994-02-10 | 1999-12-22 | Wyeth John & Brother Ltd | Pharmaceutical compositions comprising cyclohexylamine derivatives certain such novel compounds and their preparation |
| IL112568A0 (en) | 1994-02-10 | 1995-05-26 | Wyeth John & Brother Ltd | Substituted quinolines, their preparation and pharmaceutical compositions containing them |
| AU6670196A (en) | 1995-08-17 | 1997-03-12 | Takeda Chemical Industries Ltd. | Thienopyrimidine derivatives, their production and use |
| NZ333870A (en) | 1996-07-26 | 2000-08-25 | Nissan Chemical Ind Ltd | 4-amino substituted chroman derivatives |
| US6083986A (en) | 1996-07-26 | 2000-07-04 | Icagen, Inc. | Potassium channel inhibitors |
| US5935945A (en) | 1996-10-31 | 1999-08-10 | Merck & Co., Inc. | Methods of treating or preventing cardiac arrhythmia |
| US5969017A (en) | 1996-10-31 | 1999-10-19 | Merck & Co., Inc. | Methods of treating or preventing cardiac arrhythmia |
| RU2116309C1 (ru) | 1997-02-13 | 1998-07-27 | Институт медицинской паразитологии и тропической медицины им.Е.И.Марциновского | 4-[(бензо-2,1,3-тиадиазолил-4)амино]-5,6,7,8-тетрагидробензотиено [2,3-d]пиримидин, обладающий противогельминтной активностью при ларвальном альвеолярном эхинококкозе |
| US6333337B1 (en) | 1998-01-27 | 2001-12-25 | Icagen, Inc. | Potassium channel inhibitors |
| CA2334258A1 (en) | 1998-06-05 | 1999-12-09 | Icagen, Inc. | Potassium channel inhibitors |
| AU5444499A (en) | 1998-09-01 | 2000-03-21 | Nissan Chemical Industries Ltd. | Benzoxazine derivatives |
| US6194458B1 (en) | 1998-10-30 | 2001-02-27 | Merck & Co., Inc. | Benzamide potassium channel inhibitors |
| DE19929076A1 (de) | 1999-06-25 | 2000-12-28 | Aventis Pharma Gmbh | Indanylsubstituierte Benzolcarbonamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| WO2001021610A1 (en) | 1999-09-17 | 2001-03-29 | Nissan Chemical Industries, Ltd. | Benzopyran derivative |
| US6555574B1 (en) | 1999-09-24 | 2003-04-29 | Nissan Chemical Industries, Ltd. | 4-oxybenzopyran derivative |
| DE19947457A1 (de) | 1999-10-02 | 2001-04-05 | Aventis Pharma Gmbh | 2'-Substituierte 1,1'-Biphenyl-2-carbonamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie enthaltende pharmazeutische Zubereitungen |
| US6531495B1 (en) | 1999-10-02 | 2003-03-11 | Aventis Pharma Deutschland Gmbh | 2′-Substituted 1,1′-biphenyl-2-carboxamides, processes for their preparation, their use as medicaments, and pharmaceutical preparations comprising them |
| US6677371B1 (en) | 1999-10-05 | 2004-01-13 | Nissan Chemical Industries, Ltd. | 4-oxybenzopyran derivative |
| US6887870B1 (en) | 1999-10-12 | 2005-05-03 | Bristol-Myers Squibb Company | Heterocyclic sodium/proton exchange inhibitors and method |
| MY125533A (en) | 1999-12-06 | 2006-08-30 | Bristol Myers Squibb Co | Heterocyclic dihydropyrimidine compounds |
| EP1240147A1 (en) | 1999-12-21 | 2002-09-18 | Icagen, Inc. | Potassium channel inhibitors |
| CA2421819C (en) | 2000-09-20 | 2010-03-09 | Merck & Co., Inc. | Isoquinolinone potassium channel inhibitors |
| DE10054481A1 (de) | 2000-11-03 | 2002-05-08 | Aventis Pharma Gmbh | Acylaminoalkyl-substituierte Benzolsulfonamidderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| DE10059418A1 (de) | 2000-11-30 | 2002-06-20 | Aventis Pharma Gmbh | Ortho, meta-substituierte Bisarylverbindungen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| DE10060807A1 (de) | 2000-12-07 | 2002-06-20 | Aventis Pharma Gmbh | Ortho, ortho-substituierte stickstoffhaltige Bisarylverbindungen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| DE10061876A1 (de) | 2000-12-12 | 2002-06-20 | Aventis Pharma Gmbh | Arylierte Furan- und Thiophencarbonsäureamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| DE10104802A1 (de) | 2001-02-02 | 2002-08-08 | Merck Patent Gmbh | Pharmazeutische Formulierungen enthaltend Thienopirimidine und Endothelin-Rezeptor-Antagonisten (1) |
| CZ20032350A3 (en) | 2001-02-02 | 2004-03-17 | Merck Patent Gmbh | PHARMACEUTICAL FORMULATION COMPRISING PYRAZOLO 4,3-d PYRIMIDINES AND ENDOTHELIN RECEPTOR ANTAGONISTS OR THIENOPYRIMIDINES AND ENDOTHELIN RECEPTOR ANTAGONISTS |
| TW589305B (en) | 2001-02-14 | 2004-06-01 | Nissan Chemical Ind Ltd | 4-aminobenzopyran derivatives |
| DE10121002A1 (de) | 2001-04-28 | 2002-11-14 | Aventis Pharma Gmbh | Verwendung von Anthranilsäureamiden als Medikament zur Behandlung von Arrhythmien sowie sie enthaltende pharmazeutische Zubereitungen |
| DE10121003A1 (de) | 2001-04-28 | 2002-12-19 | Aventis Pharma Gmbh | Anthranilsäureamide, Verfahren zur Herstellung, ihrer Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| DE10128331A1 (de) | 2001-06-12 | 2002-12-19 | Aventis Pharma Gmbh | Anthranilsäureamide mit Heteroarylsulfonyl-Seitenkette, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltende pharmazeutische Zubereitungen |
| IL159218A0 (en) | 2001-06-25 | 2004-06-01 | Nissan Chemical Ind Ltd | Substituted benzopyran derivatives against arrhythmia |
| TW200307539A (en) | 2002-02-01 | 2003-12-16 | Bristol Myers Squibb Co | Cycloalkyl inhibitors of potassium channel function |
| GB0315950D0 (en) | 2003-06-11 | 2003-08-13 | Xention Discovery Ltd | Compounds |
| CN1823071B (zh) * | 2003-06-11 | 2012-12-19 | 润生有限公司 | 用作钾通道抑制剂的噻吩并嘧啶衍生物 |
| ZA200600197B (en) * | 2003-07-02 | 2007-06-27 | Vertex Pharma | Pyrimidines useful as modulators of voltage-gated ion channels |
| JP2007517793A (ja) | 2004-01-06 | 2007-07-05 | 大正製薬株式会社 | 環状アミノ基によって置換されたチエノピリミジン及びチエノピリジン誘導体 |
| JP2008505084A (ja) | 2004-06-29 | 2008-02-21 | アムゲン インコーポレイティッド | フラノピリミジン |
| US7576212B2 (en) | 2004-12-09 | 2009-08-18 | Xention Limited | Thieno[2,3-B] pyridines as potassium channel inhibitors |
| ATE476434T1 (de) | 2004-12-09 | 2010-08-15 | Xention Ltd | Thienopyridinderivate als kaliumkanalinhibitoren |
| US20080108611A1 (en) | 2006-01-19 | 2008-05-08 | Battista Kathleen A | Substituted thienopyrimidine kinase inhibitors |
| EP2043654A2 (en) * | 2006-06-12 | 2009-04-08 | Vertex Pharmaceuticals, Inc. | Thienopyrimidines useful as modulators of ion channels |
| DE102009039893B4 (de) | 2009-09-03 | 2012-03-29 | Bundesanstalt für Materialforschung und -Prüfung (BAM) | Verwendung eines Brennstoffs in einem selbstunterhaltenden pulsierenden Sauerstoff-Brennstoff-Verbrennungsprozess |
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