ES2329586T3 - Compuestos que tienen actividad agonista del receptor beta2 adrenergico y antagonista del receptor muscarino. - Google Patents
Compuestos que tienen actividad agonista del receptor beta2 adrenergico y antagonista del receptor muscarino. Download PDFInfo
- Publication number
- ES2329586T3 ES2329586T3 ES04811663T ES04811663T ES2329586T3 ES 2329586 T3 ES2329586 T3 ES 2329586T3 ES 04811663 T ES04811663 T ES 04811663T ES 04811663 T ES04811663 T ES 04811663T ES 2329586 T3 ES2329586 T3 ES 2329586T3
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- Spain
- Prior art keywords
- ylene
- fen
- quad
- group
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/02—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 containing two hetero rings
- C07D417/12—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 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
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Applications Claiming Priority (2)
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|---|---|---|---|
| US52423403P | 2003-11-21 | 2003-11-21 | |
| US524234P | 2003-11-21 |
Publications (1)
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|---|---|
| ES2329586T3 true ES2329586T3 (es) | 2009-11-27 |
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| Application Number | Title | Priority Date | Filing Date |
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| EP (1) | EP1685118B1 (enExample) |
| JP (2) | JP4851937B2 (enExample) |
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| AT (1) | ATE435855T1 (enExample) |
| CA (1) | CA2543858C (enExample) |
| DE (1) | DE602004021959D1 (enExample) |
| ES (1) | ES2329586T3 (enExample) |
| WO (1) | WO2005051946A2 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6693202B1 (en) * | 1999-02-16 | 2004-02-17 | Theravance, Inc. | Muscarinic receptor antagonists |
| PE20040950A1 (es) | 2003-02-14 | 2005-01-01 | Theravance Inc | DERIVADOS DE BIFENILO COMO AGONISTAS DE LOS RECEPTORES ADRENERGICOS ß2 Y COMO ANTAGONISTAS DE LOS RECEPTORES MUSCARINICOS |
| PE20050250A1 (es) * | 2003-07-17 | 2005-04-08 | Glaxo Group Ltd | Antagonistas de los receptores muscarinicos de la acetilcolina |
| AR048573A1 (es) * | 2003-07-17 | 2006-05-10 | Glaxo Group Ltd | Compuesto de 8-azoniabiciclo[3.2.1]octano sustituido en la posicion 3, composicion farmceutica que lo comprende y su uso para preparar esta ultima |
| PE20050327A1 (es) * | 2003-07-17 | 2005-06-08 | Glaxo Group Ltd | Derivados de 8-azoniabiciclo[3.2.1]octano como antagonistas de los receptores muscarinicos de la acetilcolina |
| JP2007508390A (ja) * | 2003-10-14 | 2007-04-05 | グラクソ グループ リミテッド | ムスカリン性アセチルコリン受容体アンタゴニスト |
| AU2004281167A1 (en) * | 2003-10-17 | 2005-04-28 | Glaxo Group Limited | Muscarinic acetylcholine receptor antagonists field of the invention |
| PE20050489A1 (es) * | 2003-11-04 | 2005-09-02 | Glaxo Group Ltd | Antagonistas de receptores de acetilcolina muscarinicos |
| ES2329586T3 (es) * | 2003-11-21 | 2009-11-27 | Theravance, Inc. | Compuestos que tienen actividad agonista del receptor beta2 adrenergico y antagonista del receptor muscarino. |
| WO2005087736A1 (en) * | 2004-03-11 | 2005-09-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| WO2005087236A1 (en) * | 2004-03-11 | 2005-09-22 | Glaxo Group Limited | Novel m3 muscarinic acetylcholine receptor antagonists |
| TWI341836B (en) * | 2004-03-11 | 2011-05-11 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| WO2005087735A1 (en) | 2004-03-11 | 2005-09-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| EP1723108A1 (en) * | 2004-03-11 | 2006-11-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| TW200538095A (en) * | 2004-03-11 | 2005-12-01 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| US7524962B2 (en) * | 2004-03-11 | 2009-04-28 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| JP2007528410A (ja) * | 2004-03-11 | 2007-10-11 | セラヴァンス， インコーポレーテッド | ムスカリンレセプターアンタゴニストとしての有用なビフェニル化合物 |
| MY144753A (en) | 2004-04-27 | 2011-10-31 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
| WO2005112644A2 (en) * | 2004-05-13 | 2005-12-01 | Glaxo Group Limited | Muscarinic acetylcholine receptor antagonists |
| JP2008510015A (ja) * | 2004-08-16 | 2008-04-03 | セラヴァンス， インコーポレーテッド | β２アドレナリン作用性レセプターアゴニスト活性およびムスカリン性レセプターアンタゴニスト活性を有する化合物 |
| WO2006023457A1 (en) * | 2004-08-16 | 2006-03-02 | Theravance, Inc. | COMPOUNDS HAVING β2 ADRENERGIC RECEPTOR AGONIST AND MUSCARINIC RECEPTOR ANTAGONIST ACTIVITY |
| JP2008533028A (ja) * | 2005-03-10 | 2008-08-21 | セラヴァンス， インコーポレーテッド | ムスカリン性受容体アンタゴニストとして有用なビフェニル化合物 |
| US7659403B2 (en) * | 2005-03-10 | 2010-02-09 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| TW200714587A (en) * | 2005-03-10 | 2007-04-16 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| WO2006099031A1 (en) * | 2005-03-10 | 2006-09-21 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| US7642355B2 (en) * | 2005-03-10 | 2010-01-05 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| JP2008546695A (ja) | 2005-06-13 | 2008-12-25 | セラヴァンス， インコーポレーテッド | ムスカリン受容体アンタゴニストとして有用なビフェニル化合物 |
| US8429052B2 (en) * | 2005-07-19 | 2013-04-23 | Lincoln National Life Insurance Company | Method and system for providing employer-sponsored retirement plan |
| JP2009503099A (ja) * | 2005-08-02 | 2009-01-29 | グラクソ グループ リミテッド | Ｍ３ムスカリン性アセチルコリン受容体アンタゴニスト |
| EP1937230A4 (en) * | 2005-08-02 | 2009-08-26 | Glaxo Group Ltd | M3-MUSCARIN ACETYLCHOLIN RECEPTOR ANTAGONISTS |
| JP2009504768A (ja) * | 2005-08-18 | 2009-02-05 | グラクソ グループ リミテッド | ムスカリン性アセチルコリン受容体アンタゴニスト |
| GB0602778D0 (en) * | 2006-02-10 | 2006-03-22 | Glaxo Group Ltd | Novel compound |
| TW200811105A (en) | 2006-04-25 | 2008-03-01 | Theravance Inc | Dialkylphenyl compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity |
| TW200811104A (en) * | 2006-04-25 | 2008-03-01 | Theravance Inc | Crystalline forms of a dimethylphenyl compound |
| TW201036957A (en) | 2009-02-20 | 2010-10-16 | Astrazeneca Ab | Novel salt 628 |
| US8519138B2 (en) * | 2009-04-14 | 2013-08-27 | Glaxo Group Limited | Process for the preparation of a biphenyl-2-yl carbamic acid ester |
| PT3111927T (pt) | 2009-05-29 | 2020-03-03 | Pearl Therapeutics Inc | Composições para administração respiratória de agentes ativos e métodos e sistemas associados |
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| WO2011081937A1 (en) | 2009-12-15 | 2011-07-07 | Gilead Sciences, Inc. | Corticosteroid-beta-agonist-muscarinic antagonist compounds for use in therapy |
| RS54201B1 (sr) * | 2010-07-13 | 2015-12-31 | Theravance Biopharma R&D Ip, Llc | Postupak za pripremu bifenil-2-ilkarbaminske kiseline |
| WO2012032546A2 (en) * | 2010-09-08 | 2012-03-15 | Cadila Healthcare Limited | Process for the preparation of salmeterol and its intermediates |
| GB201016912D0 (en) | 2010-10-07 | 2010-11-24 | Astrazeneca Ab | Novel combination |
| CN105106200A (zh) * | 2011-05-17 | 2015-12-02 | 珍珠治疗公司 | 用于呼吸递送两种或多种活性剂的组合物、方法和系统 |
| RS54365B1 (sr) | 2011-06-10 | 2016-04-28 | Chiesi Farmaceutici S.P.A. | Jedinjenja koja imaju aktivnost antagonista muskarinskih receptora i agonist beta2 adrenergičnog receptora |
| RU2606121C2 (ru) | 2011-06-10 | 2017-01-10 | КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. | Соединения, обладающие антагонистической активностью в отношении мускариновых рецепторов и агонистической активностью в отношении бета2-адренорецепторов |
| JO3192B1 (ar) | 2011-09-06 | 2018-03-08 | Novartis Ag | مركب بنزوثيازولون |
| CN104854105B (zh) | 2012-12-06 | 2017-05-17 | 奇斯药制品公司 | 具有毒蕈碱受体拮抗剂和β2肾上腺素能受体激动剂活性的化合物 |
| HRP20180915T1 (hr) | 2012-12-06 | 2018-07-27 | Chiesi Farmaceutici S.P.A. | Spojevi koji imaju aktivnost kao antagonist muskarinskog receptora i kao agonist beta2 adrenergijskog receptora |
| TWI703138B (zh) | 2015-02-12 | 2020-09-01 | 義大利商吉斯藥品公司 | 具有蕈毒鹼受體拮抗劑及β２腎上腺素受體促效劑活性之化合物 |
| CN107074816B (zh) * | 2015-03-27 | 2020-07-17 | 四川海思科制药有限公司 | 一种杂环衍生物及其制备方法和在医药上的用途 |
| AR104828A1 (es) | 2015-06-01 | 2017-08-16 | Chiesi Farm Spa | COMPUESTOS CON ACTIVIDAD ANTAGONISTA DE LOS RECEPTORES MUSCARÍNICOS Y ACTIVIDAD AGONISTA DEL RECEPTOR b2 ADRENÉRGICO |
| WO2017093208A1 (en) | 2015-12-03 | 2017-06-08 | Chiesi Farmaceutici S.P.A. | Compounds having muscarinic receptor antagonist and beta2 adrenergic receptor agonist activity |
| CN107849035B (zh) * | 2015-12-29 | 2021-12-10 | 四川海思科制药有限公司 | 一种苯基杂环衍生物及其在医药上的用途 |
| KR20180100106A (ko) * | 2016-01-22 | 2018-09-07 | 스촨 하이스코 파마수티컬 씨오., 엘티디 | 질소함유 헤테로 고리 아미드 유도체 및 그 제조방법과 약학적 용도 |
| WO2018011090A1 (en) | 2016-07-13 | 2018-01-18 | Chiesi Farmaceutici S.P.A. | Hydroxyquinolinone compounds having muscarinic receptor antagonist and beta2 adrenergic receptor agonist activity |
| ES2836113T3 (es) | 2016-12-14 | 2021-06-24 | Beijing Showby Pharmaceutical Co Ltd | Clase de compuestos bifuncionales con estructura de sal de amonio cuaternario |
| CN106632257B (zh) * | 2016-12-15 | 2019-02-12 | 上海市奉贤区中心医院 | Gsk961081及其中间体的合成方法 |
| WO2019015639A1 (zh) * | 2017-07-21 | 2019-01-24 | 四川海思科制药有限公司 | 一种氮杂环酰胺衍生物组合物及其制备 |
| WO2019015640A1 (zh) * | 2017-07-21 | 2019-01-24 | 四川海思科制药有限公司 | 一种氮杂环酰胺衍生物的盐、其晶型及其制备方法和用途 |
| CN111423434A (zh) * | 2019-01-09 | 2020-07-17 | 四川海思科制药有限公司 | 一种碳酰胺衍生物及其制备方法 |
| CN115093365B (zh) * | 2022-07-25 | 2023-07-25 | 沈阳药科大学 | 一种雷芬那辛的合成方法 |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4181802A (en) * | 1978-05-11 | 1980-01-01 | Janssen Pharmaceutica N.V. | 1-(Heterocyclylalkyl)-1,3-dihydro-2-H-benzimidazole-2-ones |
| DK443489D0 (da) | 1989-09-08 | 1989-09-08 | Ferrosan As | Substituerede urinstofforbindelser, deres fremstilling og anvendelse |
| GB9210632D0 (en) | 1992-05-19 | 1992-07-01 | Fisons Plc | Compounds |
| GB9211172D0 (en) | 1992-05-27 | 1992-07-08 | Fisons Plc | Compounds |
| IE914003A1 (en) | 1990-11-20 | 1992-05-20 | Astra Pharma Prod | Biologically Active Amines |
| US5648370A (en) | 1990-11-20 | 1997-07-15 | Astra Pharmaceuticals Limited | 7-(2-aminoethyl) benzothiazolones |
| DK0640081T3 (da) | 1992-03-31 | 2000-06-19 | Glaxo Group Ltd | Substituerede phenylcarbarmater og phenylurinstoffer, deres fremstilling og deres anvendelse som 5-HT4-antagonister |
| CA2123728A1 (en) | 1993-05-21 | 1994-11-22 | Noriyoshi Sueda | Urea derivatives and their use as acat inhibitors |
| AU7545894A (en) | 1993-09-02 | 1995-03-22 | Yamanouchi Pharmaceutical Co., Ltd. | Carbamate derivative and medicine containing the same |
| CA2182568A1 (en) | 1994-02-10 | 1995-08-17 | Makoto Takeuchi | Novel carbamate derivative and medicinal composition containing the same |
| TW356468B (en) | 1995-09-15 | 1999-04-21 | Astra Pharma Prod | Benzothiazolone compounds useful as beta2-adrenoreceptor and dopamine DA2 receptor agonists process for preparing same and pharmaceutical compositions containing same |
| EP0863141B1 (en) | 1995-10-13 | 2001-09-12 | Banyu Pharmaceutical Co., Ltd. | Substituted heteroaromatic derivatives |
| GB9526511D0 (en) | 1995-12-23 | 1996-02-28 | Astra Pharma Prod | Pharmaceutically active compounds |
| PE92198A1 (es) | 1996-08-01 | 1999-01-09 | Banyu Pharma Co Ltd | Derivados de 1,4-piperidina disustituida que contienen fluor |
| WO1999009018A1 (en) | 1997-08-14 | 1999-02-25 | Kirin Beer Kabushiki Kaisha | BENZOTHIAZOLONE DERIVATIVES HAVING SELECTIVE β2 RECEPTOR AGONIST ACTIVITY |
| WO1999031086A1 (en) | 1997-12-12 | 1999-06-24 | Smithkline Beecham Plc | Quinolinepiperazine and quinolinepiperidine derivatives, their preparation and their use as combined 5-ht1a, 5-ht1b and 5-ht1d receptor antagonists |
| JP2002517464A (ja) | 1998-06-08 | 2002-06-18 | アドバンスド メディスン インコーポレーテッド | ムスカリン性レセプターアンタゴニスト |
| US6693202B1 (en) | 1999-02-16 | 2004-02-17 | Theravance, Inc. | Muscarinic receptor antagonists |
| SE9900693D0 (sv) | 1999-02-26 | 1999-02-26 | Astra Pharma Prod | Novel process |
| DE19921693A1 (de) * | 1999-05-12 | 2000-11-16 | Boehringer Ingelheim Pharma | Neuartige Arzneimittelkompositionen auf der Basis von anticholinergisch wirksamen Verbindungen und ß-Mimetika |
| SE9902936D0 (sv) | 1999-08-18 | 1999-08-18 | Astra Pharma Prod | Pharmaceutical compositions |
| SE9902938D0 (sv) | 1999-08-18 | 1999-08-18 | Astra Pharma Prod | Pharmaceutical compositions |
| SE9902937D0 (sv) | 1999-08-18 | 1999-08-18 | Astra Pharma Prod | Pharmaceutical compositions |
| SE9902935D0 (sv) | 1999-08-18 | 1999-08-18 | Astra Pharma Prod | Pharmaceutical compositions |
| UA73543C2 (uk) | 1999-12-07 | 2005-08-15 | Тераванс, Інк. | Похідні сечовини, фармацевтична композиція та застосування похідного при приготуванні лікарського засобу для лікування захворювання, яке опосередковується мускариновим рецептором |
| AU783095B2 (en) | 1999-12-07 | 2005-09-22 | Theravance Biopharma R&D Ip, Llc | Carbamate derivatives having muscarinic receptor antagonist activity |
| US6506901B2 (en) * | 2000-07-17 | 2003-01-14 | Wyeth | Substituted 2-(S)-hydroxy-3-(piperidin-4-yl-methylamino)-propyl ethers and substituted 2-aryl-2-(R)-hydroxy-1-(piperidin-4-yl-methyl)-ethylamine β-3 adrenergic receptor agonists |
| JP4445704B2 (ja) | 2000-12-22 | 2010-04-07 | アルミラル・ソシエダッド・アノニマ | キヌクリジンカルバメート誘導体およびｍ３アンダゴニストとしてのそれらの使用 |
| US20030018019A1 (en) | 2001-06-23 | 2003-01-23 | Boehringer Ingelheim Pharma Kg | Pharmaceutical compositions based on anticholinergics, corticosteroids and betamimetics |
| TW200410951A (en) | 2002-08-06 | 2004-07-01 | Glaxo Group Ltd | M3 muscarinic acetylcholine receptor antagonists |
| PE20050130A1 (es) | 2002-08-09 | 2005-03-29 | Novartis Ag | Compuestos organicos |
| PE20040950A1 (es) | 2003-02-14 | 2005-01-01 | Theravance Inc | DERIVADOS DE BIFENILO COMO AGONISTAS DE LOS RECEPTORES ADRENERGICOS ß2 Y COMO ANTAGONISTAS DE LOS RECEPTORES MUSCARINICOS |
| US7094790B2 (en) * | 2003-05-07 | 2006-08-22 | Abbott Laboratories | Fused bicyclic-substituted amines as histamine-3 receptor ligands |
| ES2329586T3 (es) * | 2003-11-21 | 2009-11-27 | Theravance, Inc. | Compuestos que tienen actividad agonista del receptor beta2 adrenergico y antagonista del receptor muscarino. |
-
2004
- 2004-11-19 ES ES04811663T patent/ES2329586T3/es not_active Expired - Lifetime
- 2004-11-19 WO PCT/US2004/038975 patent/WO2005051946A2/en not_active Ceased
- 2004-11-19 DE DE602004021959T patent/DE602004021959D1/de not_active Expired - Lifetime
- 2004-11-19 CA CA2543858A patent/CA2543858C/en not_active Expired - Fee Related
- 2004-11-19 AT AT04811663T patent/ATE435855T1/de not_active IP Right Cessation
- 2004-11-19 CN CNB2004800342018A patent/CN100569760C/zh not_active Expired - Fee Related
- 2004-11-19 EP EP04811663A patent/EP1685118B1/en not_active Expired - Lifetime
- 2004-11-19 US US10/992,927 patent/US7345060B2/en not_active Expired - Fee Related
- 2004-11-19 JP JP2006541552A patent/JP4851937B2/ja not_active Expired - Fee Related
-
2007
- 2007-12-11 US US12/001,363 patent/US7838535B2/en not_active Expired - Fee Related
- 2007-12-11 US US12/001,362 patent/US7842704B2/en not_active Expired - Fee Related
-
2010
- 2010-10-13 US US12/903,365 patent/US8247564B2/en not_active Expired - Fee Related
-
2011
- 2011-05-30 JP JP2011121065A patent/JP2011190271A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005051946A2 (en) | 2005-06-09 |
| US7345060B2 (en) | 2008-03-18 |
| US8247564B2 (en) | 2012-08-21 |
| CN1882556A (zh) | 2006-12-20 |
| DE602004021959D1 (de) | 2009-08-20 |
| EP1685118A2 (en) | 2006-08-02 |
| US20080096911A1 (en) | 2008-04-24 |
| US20050113417A1 (en) | 2005-05-26 |
| JP2011190271A (ja) | 2011-09-29 |
| CA2543858A1 (en) | 2005-06-09 |
| CA2543858C (en) | 2014-04-15 |
| CN100569760C (zh) | 2009-12-16 |
| US7838535B2 (en) | 2010-11-23 |
| WO2005051946A3 (en) | 2005-07-14 |
| JP2007514662A (ja) | 2007-06-07 |
| EP1685118B1 (en) | 2009-07-08 |
| US20080097105A1 (en) | 2008-04-24 |
| JP4851937B2 (ja) | 2012-01-11 |
| US7842704B2 (en) | 2010-11-30 |
| US20110034694A1 (en) | 2011-02-10 |
| ATE435855T1 (de) | 2009-07-15 |
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