ES2359673T3 - Compuestos de benzoimidazolona-carboxamida como agonista del receptor 5-ht4. - Google Patents
Compuestos de benzoimidazolona-carboxamida como agonista del receptor 5-ht4. Download PDFInfo
- Publication number
- ES2359673T3 ES2359673T3 ES06772173T ES06772173T ES2359673T3 ES 2359673 T3 ES2359673 T3 ES 2359673T3 ES 06772173 T ES06772173 T ES 06772173T ES 06772173 T ES06772173 T ES 06772173T ES 2359673 T3 ES2359673 T3 ES 2359673T3
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- acid
- isopropyl
- azabicyclo
- oxo
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
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- 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
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
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- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (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)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US68804805P | 2005-06-07 | 2005-06-07 | |
| US688048P | 2005-06-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2359673T3 true ES2359673T3 (es) | 2011-05-25 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06772173T Active ES2359673T3 (es) | 2005-06-07 | 2006-06-06 | Compuestos de benzoimidazolona-carboxamida como agonista del receptor 5-ht4. |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US7317022B2 (https=) |
| EP (1) | EP1902053B1 (https=) |
| JP (1) | JP5086248B2 (https=) |
| AT (1) | ATE495171T1 (https=) |
| DE (1) | DE602006019595D1 (https=) |
| ES (1) | ES2359673T3 (https=) |
| WO (1) | WO2006133104A2 (https=) |
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| TWI351282B (en) | 2004-04-07 | 2011-11-01 | Theravance Inc | Quinolinone-carboxamide compounds as 5-ht4 recepto |
| US7399862B2 (en) * | 2004-11-05 | 2008-07-15 | Theravance, Inc. | 5-HT4 receptor agonist compounds |
| WO2006052889A2 (en) * | 2004-11-05 | 2006-05-18 | Theravance, Inc. | Quinolinone-carboxamide compounds |
| CA2588037A1 (en) * | 2004-12-22 | 2006-06-29 | Theravance, Inc. | Indazole-carboxamide compounds |
| CN101163701A (zh) * | 2005-03-02 | 2008-04-16 | 施万制药 | 作为5-ht4受体激动剂的喹啉酮化合物 |
| MY143574A (en) | 2005-11-22 | 2011-05-31 | Theravance Inc | Carbamate compounds as 5-ht4 receptor agonists |
| EP2241567A4 (en) * | 2008-02-13 | 2011-11-09 | Eisai R&D Man Co Ltd | Bicycloamine DERIVATIVE |
| US8349852B2 (en) | 2009-01-13 | 2013-01-08 | Novartis Ag | Quinazolinone derivatives useful as vanilloid antagonists |
| AR080056A1 (es) | 2010-02-01 | 2012-03-07 | Novartis Ag | Derivados de ciclohexil-amida como antagonistas de los receptores de crf |
| WO2011092290A1 (en) | 2010-02-01 | 2011-08-04 | Novartis Ag | Pyrazolo[5,1b]oxazole derivatives as crf-1 receptor antagonists |
| EP2531490B1 (en) | 2010-02-02 | 2014-10-15 | Novartis AG | Cyclohexyl amide derivatives as crf receptor antagonists |
| MX2020003242A (es) | 2017-09-22 | 2020-09-18 | Jubilant Epipad LLC | Compuestos heterociclicos como inhibidores de pad. |
| AU2018352142B2 (en) | 2017-10-18 | 2022-08-25 | Jubilant Epipad LLC | Imidazo-pyridine compounds as PAD inhibitors |
| KR20200085836A (ko) | 2017-11-06 | 2020-07-15 | 주빌런트 프로델 엘엘씨 | Pd1/pd-l1 활성화 억제제로서의 피리미딘 유도체 |
| BR112020010322A2 (pt) | 2017-11-24 | 2020-11-17 | Jubilant Episcribe Llc | composto da fórmula i; composto da fórmula ia; composto da fórmula ib; processo de preparação de compostos da fórmula i; composição farmacêutica; método para o tratamento e/ou prevenção de várias doenças; uso dos compostos; método para o tratamento de câncer; e método para o tratamento e/ou prevenção de uma afecção mediada por prmt5 ou um distúrbio proliferativo ou câncer |
| SG11202008950PA (en) | 2018-03-13 | 2020-10-29 | Jubilant Prodel LLC | Bicyclic compounds as inhibitors of pd1/pd-l1 interaction/activation |
| CN115073311B (zh) * | 2022-03-23 | 2023-05-23 | 河南大学 | 一种高效制备n,n′-二（2羟乙基）苯胺的合成方法 |
Family Cites Families (16)
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| US5223511A (en) | 1987-09-23 | 1993-06-29 | Boehringer Ingelheim Italia S.P.A. | Benzimidazoline-2-oxo-1-carboxylic acid compounds useful as 5-HT receptor antagonists |
| IT1231413B (it) | 1987-09-23 | 1991-12-04 | Angeli Inst Spa | Derivati dell'acido benzimidazolin-2-osso-1-carbossilico utili come antagonisti dei recettori 5-ht |
| JP3829879B2 (ja) | 1994-05-18 | 2006-10-04 | 大正製薬株式会社 | キノリンカルボン酸誘導体 |
| IT1275903B1 (it) | 1995-03-14 | 1997-10-24 | Boehringer Ingelheim Italia | Esteri e ammidi della 1,4-piperidina disostituita |
| US6069152A (en) * | 1997-10-07 | 2000-05-30 | Eli Lilly And Company | 5-HT4 agonists and antagonists |
| GB9721139D0 (en) * | 1997-10-07 | 1997-12-03 | Glaxo Group Ltd | Medicaments |
| IT1298271B1 (it) | 1998-02-18 | 1999-12-20 | Boehringer Ingelheim Italia | Esteri ed ammidi dell'acido 2-oxo-2,3-diidro-benzimidazol-1- carbossilico |
| EP1173168A2 (en) | 1999-04-28 | 2002-01-23 | Respiratorius AB | Compound for use as a medicament for treatment of disorders involving bronchocontraction |
| CN1355698A (zh) * | 1999-06-15 | 2002-06-26 | 呼吸器有限公司 | 可用作治疗有关支气管收缩的机能障碍的药物的化合物 |
| IT1313625B1 (it) | 1999-09-22 | 2002-09-09 | Boehringer Ingelheim Italia | Derivati benzimidazolonici aventi affinita' mista per i recettori diserotonina e dopamina. |
| KR100738784B1 (ko) | 2003-09-03 | 2007-07-12 | 화이자 인코포레이티드 | 5-ｈｔ4 수용체 효능 활성을 갖는 벤즈이미다졸론 |
| TW200533348A (en) | 2004-02-18 | 2005-10-16 | Theravance Inc | Indazole-carboxamide compounds as 5-ht4 receptor agonists |
| TWI351282B (en) | 2004-04-07 | 2011-11-01 | Theravance Inc | Quinolinone-carboxamide compounds as 5-ht4 recepto |
| WO2006052889A2 (en) | 2004-11-05 | 2006-05-18 | Theravance, Inc. | Quinolinone-carboxamide compounds |
| US7399862B2 (en) | 2004-11-05 | 2008-07-15 | Theravance, Inc. | 5-HT4 receptor agonist compounds |
| CA2588037A1 (en) | 2004-12-22 | 2006-06-29 | Theravance, Inc. | Indazole-carboxamide compounds |
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|---|---|
| US20060276482A1 (en) | 2006-12-07 |
| JP2009512624A (ja) | 2009-03-26 |
| DE602006019595D1 (de) | 2011-02-24 |
| EP1902053B1 (en) | 2011-01-12 |
| JP5086248B2 (ja) | 2012-11-28 |
| US20080070923A1 (en) | 2008-03-20 |
| EP1902053A2 (en) | 2008-03-26 |
| US7317022B2 (en) | 2008-01-08 |
| ATE495171T1 (de) | 2011-01-15 |
| WO2006133104A2 (en) | 2006-12-14 |
| US7772239B2 (en) | 2010-08-10 |
| WO2006133104A3 (en) | 2007-04-26 |
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