AU722472B2 - Quinoline carboxamides as TNF inhibitors and as PDE-IV inhibitors - Google Patents
Quinoline carboxamides as TNF inhibitors and as PDE-IV inhibitors Download PDFInfo
- Publication number
- AU722472B2 AU722472B2 AU29058/97A AU2905897A AU722472B2 AU 722472 B2 AU722472 B2 AU 722472B2 AU 29058/97 A AU29058/97 A AU 29058/97A AU 2905897 A AU2905897 A AU 2905897A AU 722472 B2 AU722472 B2 AU 722472B2
- Authority
- AU
- Australia
- Prior art keywords
- methoxyquinoline
- carboxamide
- disease
- compound
- dichloropyridin
- 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.)
- Ceased
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 239000006228 supernatant Substances 0.000 description 1
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- 239000000375 suspending agent Substances 0.000 description 1
- 239000002278 tabletting lubricant Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
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- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Classifications
-
- 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
- A61K31/47—Quinolines; Isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom 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
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
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)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Communicable Diseases (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9610506.9A GB9610506D0 (en) | 1996-05-20 | 1996-05-20 | Novel compounds |
| GB9610506 | 1996-05-20 | ||
| GBGB9623234.3A GB9623234D0 (en) | 1996-11-07 | 1996-11-07 | Novel compounds |
| GB9623234 | 1996-11-07 | ||
| GB9626883 | 1996-12-24 | ||
| GBGB9626883.4A GB9626883D0 (en) | 1996-12-24 | 1996-12-24 | Compounds |
| GB9708072 | 1997-04-22 | ||
| GBGB9708072.5A GB9708072D0 (en) | 1997-04-22 | 1997-04-22 | Compounds |
| PCT/GB1997/001359 WO1997044036A1 (en) | 1996-05-20 | 1997-05-20 | Quinoline carboxamides as tnf inhibitors and as pde-iv inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2905897A AU2905897A (en) | 1997-12-09 |
| AU722472B2 true AU722472B2 (en) | 2000-08-03 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU29058/97A Ceased AU722472B2 (en) | 1996-05-20 | 1997-05-20 | Quinoline carboxamides as TNF inhibitors and as PDE-IV inhibitors |
Country Status (19)
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|---|---|
| US (1) | US5804588A (enExample) |
| EP (1) | EP0952832B1 (enExample) |
| JP (1) | JP2000510865A (enExample) |
| KR (1) | KR20000065219A (enExample) |
| CN (1) | CN1148189C (enExample) |
| AT (1) | ATE406163T1 (enExample) |
| AU (1) | AU722472B2 (enExample) |
| BR (1) | BR9709015A (enExample) |
| CA (1) | CA2252531A1 (enExample) |
| CZ (1) | CZ296163B6 (enExample) |
| DE (1) | DE69738949D1 (enExample) |
| IL (1) | IL126557A (enExample) |
| NO (1) | NO312099B1 (enExample) |
| NZ (1) | NZ332341A (enExample) |
| PL (1) | PL329922A1 (enExample) |
| RU (1) | RU2170730C2 (enExample) |
| SK (1) | SK283162B6 (enExample) |
| TR (1) | TR199802385T2 (enExample) |
| WO (1) | WO1997044036A1 (enExample) |
Families Citing this family (87)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6008230A (en) * | 1995-10-16 | 1999-12-28 | Fujisawa Pharmaceutical Co., Ltd. | Quinoline compounds as H+ -ATPases |
| GB9712761D0 (en) * | 1997-06-17 | 1997-08-20 | Chiroscience Ltd | Quinolines and their therapeutic use |
| US6262070B1 (en) | 1998-11-04 | 2001-07-17 | Darwin Discovery Ltd. | Heterocyclic compounds and their therapeutic use |
| GB9824160D0 (en) * | 1998-11-04 | 1998-12-30 | Darwin Discovery Ltd | Heterocyclic compounds and their therapeutic use |
| SI1212089T1 (sl) | 1999-08-21 | 2006-08-31 | Altana Pharma Ag | Sinergisticna kombinacija roflumilasta in salmeterola |
| WO2001032658A1 (en) * | 1999-11-02 | 2001-05-10 | Ajinomoto Co., Inc. | Polyazanaphthalene compound and medicinal use thereof |
| JP4603646B2 (ja) * | 1999-11-15 | 2010-12-22 | 富士フイルムファインケミカルズ株式会社 | 新規なジピリジル誘導体 |
| US7217722B2 (en) | 2000-02-01 | 2007-05-15 | Kirin Beer Kabushiki Kaisha | Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same |
| GB0003256D0 (en) * | 2000-02-11 | 2000-04-05 | Darwin Discovery Ltd | Heterocyclic compounds and their therapeutic use |
| US6521618B2 (en) | 2000-03-28 | 2003-02-18 | Wyeth | 3-cyanoquinolines, 3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors |
| DE10035928A1 (de) | 2000-07-21 | 2002-03-07 | Asta Medica Ag | Neue Heteroaryl-Derivate und deren Verwendung als Arzneimittel |
| EP1310488A4 (en) * | 2000-08-09 | 2005-08-10 | Mitsubishi Pharma Corp | CONDENSED BICYCLIC AMIDE COMPOUNDS AND MEDICAL USES THEREOF |
| US6953774B2 (en) | 2000-08-11 | 2005-10-11 | Applied Research Systems Ars Holding N.V. | Methods of inducing ovulation |
| JP2002300373A (ja) * | 2001-03-30 | 2002-10-11 | Minolta Co Ltd | 画像処理方法、画像処理装置、記録媒体及びプログラム |
| CA2447619A1 (en) | 2001-05-23 | 2002-11-28 | Tanabe Seiyaku Co., Ltd. | A composition for accelerating bone fracture healing |
| WO2002094320A1 (en) * | 2001-05-23 | 2002-11-28 | Tanabe Seiyaku Co., Ltd. | Therapeutic compositions for repairing chondropathy |
| DE60215178T2 (de) | 2001-07-16 | 2007-08-23 | Astrazeneca Ab | Quinolin-derivate und ihre verwendung als inhibitoren der tyrosine kinase |
| EP1417204B1 (en) * | 2001-08-15 | 2006-01-18 | E. I. du Pont de Nemours and Company | Ortho-heterocyclic substituted aryl amides for controlling invertebrate pests |
| ES2293965T3 (es) | 2001-12-14 | 2008-04-01 | Laboratoires Serono Sa | Metodo de inducir la ovulacion utilizando un modulador no polipeptidico de los niveles de camp. |
| MY140561A (en) | 2002-02-20 | 2009-12-31 | Nycomed Gmbh | Dosage form containing pde 4 inhibitor as active ingredient |
| SE0200920D0 (sv) * | 2002-03-25 | 2002-03-25 | Astrazeneca Ab | Novel compounds |
| ES2195785B1 (es) * | 2002-05-16 | 2005-03-16 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| AU2002950217A0 (en) | 2002-07-16 | 2002-09-12 | Prana Biotechnology Limited | 8- Hydroxy Quinoline Derivatives |
| ES2211344B1 (es) * | 2002-12-26 | 2005-10-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| TWI324150B (en) * | 2003-02-28 | 2010-05-01 | Novartis Ag | Process for preparing 5-[(r)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1h)-quinolin-2-one salt |
| JP2006522151A (ja) | 2003-04-01 | 2006-09-28 | アプライド リサーチ システムズ エーアールエス ホールディング ナームロゼ フェンノートシャップ | 不妊症におけるホスホジエステラーゼ阻害剤 |
| TWI324151B (en) * | 2003-04-02 | 2010-05-01 | Novartis Ag | Process for the preparation of 5-(haloacetyl)-8-substituted oxy-(1h)-quinolin-2-ones |
| RU2350354C2 (ru) * | 2003-05-29 | 2009-03-27 | Астразенека Аб | ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ АНТАГОНИСТ Р2Х7 РЕЦЕПТОРА И ФАКТОР НЕКРОЗА ОПУХОЛИ α |
| US20070281931A1 (en) * | 2003-05-29 | 2007-12-06 | Nigel Boughton-Smith | Pharmaceutical Composition Containing a P2x7 Receptor Antagonist and Methotrexate |
| EP1644041A1 (en) * | 2003-05-29 | 2006-04-12 | AstraZeneca AB | A pharmaceutical composition comprising a p2x7 antagonist and sulfasalazine |
| GB0312609D0 (en) * | 2003-06-02 | 2003-07-09 | Astrazeneca Ab | Novel compounds |
| SE0302139D0 (sv) * | 2003-07-28 | 2003-07-28 | Astrazeneca Ab | Novel compounds |
| SE0302192D0 (sv) * | 2003-08-08 | 2003-08-08 | Astrazeneca Ab | Novel compounds |
| CA2538591A1 (en) * | 2003-09-15 | 2005-03-31 | Schering Corporation | Synthesis of quinoline 5-carboxamides useful for the preparation of pde iv inhibitors |
| SE0302488D0 (sv) * | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | New combination |
| AU2004298486A1 (en) | 2003-12-12 | 2005-06-30 | Wyeth | Quinolines useful in treating cardiovascular disease |
| DK2666481T3 (en) * | 2003-12-26 | 2019-02-25 | Masatoshi Hagiwara | A method for regulating the phosphorylation of SR protein and antiviral agents comprising an SR protein activity regulator as the active ingredient |
| EA010369B1 (ru) | 2004-02-04 | 2008-08-29 | Пфайзер Продактс Инк. | Замещенные хинолиновые соединения |
| WO2005097058A2 (en) * | 2004-04-01 | 2005-10-20 | F. Hoffmann-La Roche Ag | Cyclodextrin inclusions complexes of pyrimidine-2,4,6-triones |
| PE20060241A1 (es) * | 2004-05-18 | 2006-04-01 | Schering Corp | 2-quinolil-oxazoles sustituidos como inhibidores de pde4 |
| ES2251866B1 (es) * | 2004-06-18 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| ES2251867B1 (es) * | 2004-06-21 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| GB0413960D0 (en) * | 2004-06-22 | 2004-07-28 | Novartis Ag | Organic compounds |
| WO2006002421A2 (en) * | 2004-06-24 | 2006-01-05 | Vertex Pharmaceuticals Incorporated | Modulators of atp-binding cassette transporters |
| US8354427B2 (en) | 2004-06-24 | 2013-01-15 | Vertex Pharmaceutical Incorporated | Modulators of ATP-binding cassette transporters |
| SA05260265A (ar) * | 2004-08-30 | 2005-12-03 | استرازينيكا ايه بي | مركبات جديدة |
| AR051213A1 (es) * | 2004-10-12 | 2006-12-27 | Actelion Pharmaceuticals Ltd | 1-(2-(4-bencil-4-hidroxi-piperidin-1-il)-etil)-3-(2-metil-quinolin-4-il)-urea como una sal sulfato cristalina |
| ATE517882T1 (de) * | 2004-10-19 | 2011-08-15 | Hoffmann La Roche | Chinolinderivate |
| SE0402925D0 (sv) * | 2004-11-30 | 2004-11-30 | Astrazeneca Ab | Novel Compounds |
| EP1917245A1 (de) | 2005-08-21 | 2008-05-07 | Abbott GmbH & Co. KG | Heterocyclische verbindungen und ihre verwendung als bindungspartner für 5-ht5-rezeptoren |
| EP2258358A3 (en) | 2005-08-26 | 2011-09-07 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
| US7678363B2 (en) | 2005-08-26 | 2010-03-16 | Braincells Inc | Methods of treating psychiatric conditions comprising administration of muscarinic agents in combination with SSRIs |
| EP2377530A3 (en) | 2005-10-21 | 2012-06-20 | Braincells, Inc. | Modulation of neurogenesis by PDE inhibition |
| EP1942879A1 (en) | 2005-10-31 | 2008-07-16 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20090105272A1 (en) * | 2005-12-24 | 2009-04-23 | Grootenhuis Peter D J | Prodrugs of modulators of ABC transporters |
| AU2006332726B2 (en) * | 2005-12-28 | 2012-12-13 | Vertex Pharmaceuticals Incorporated. | Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide |
| KR100821649B1 (ko) * | 2006-01-24 | 2008-04-11 | 서울시립대학교 산학협력단 | 클리오퀴놀을 유효성분으로 포함하는 ＨＩＦ-1α 활성제 |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| WO2007134136A2 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| NZ574070A (en) * | 2006-07-11 | 2011-12-22 | Schering Corp | Xinafoate salt of a substituted 5-oxazol-2-yl-quinoline compound |
| US20100056791A1 (en) | 2006-09-01 | 2010-03-04 | Yasushi Kohno | Pyrazolopyridine carboxamide derivative and phosphodiesterase (pde) inhibitor containing the same |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| CL2007003874A1 (es) * | 2007-01-03 | 2008-05-16 | Boehringer Ingelheim Int | Compuestos derivados de benzamida; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar enfermedades cardiovasculares, hipertension, aterosclerosis, reestenosis, ictus, insuficiencia cardiaca, lesion isquemica, hipertensio |
| ES2306595B1 (es) * | 2007-02-09 | 2009-09-11 | Laboratorios Almirall S.A. | Sal de napadisilato de 5-(2-((6-(2,2-difluoro-2-feniletoxi)hexil)amino)-1-hidroxietil)-8-hidroxiquinolin-2(1h)-ona como agonista del receptor adrenergico beta2. |
| ES2320954B1 (es) * | 2007-03-02 | 2010-03-16 | Laboratorio Almirall S.A. | Nuevo procedimiento de preparacion de 3-metil-4-fenilisoxazolo (3,4-d)iridazin-7(6h)-ona. |
| ES2388454T3 (es) * | 2007-03-22 | 2012-10-15 | Astrazeneca Ab | Derivados de quinolina para el tratamiento de enfermedades inflamatorias |
| US9321730B2 (en) | 2007-08-21 | 2016-04-26 | The Hong Kong Polytechnic University | Method of making and administering quinoline derivatives as anti-cancer agents |
| US8106073B2 (en) | 2007-11-30 | 2012-01-31 | Astrazeneca Ab | Quinoline derivatives 057 |
| US20100074949A1 (en) | 2008-08-13 | 2010-03-25 | William Rowe | Pharmaceutical composition and administration thereof |
| US12458635B2 (en) | 2008-08-13 | 2025-11-04 | Vertex Pharmaceuticals Incorporated | Pharmaceutical composition and administrations thereof |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| AU2010226400B2 (en) | 2009-03-20 | 2016-07-14 | Vertex Pharmaceuticals Incorporated | Process for making modulators of cystic fibrosis transmembrane conductance regulator |
| JP2011042643A (ja) * | 2009-07-24 | 2011-03-03 | Bayer Cropscience Ag | 殺虫性カルボキサミド類 |
| CA2796826A1 (en) | 2010-05-10 | 2011-11-17 | Gilead Sciences, Inc. | Bifunctional quinoline derivatives |
| AR081377A1 (es) | 2010-05-10 | 2012-08-29 | Gilead Sciences Inc | Compuestos de pirazolopiridina bifuncionales |
| US20140275224A1 (en) * | 2010-11-05 | 2014-09-18 | Regents Of The University Of Minnesota | Cytosine deaminase modulators for enhancement of dna transfection |
| US8802700B2 (en) | 2010-12-10 | 2014-08-12 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-Binding Cassette transporters |
| CN102603628B (zh) | 2010-12-22 | 2016-08-17 | 香港理工大学 | 作为抗癌试剂的喹啉衍生物 |
| US20150119399A1 (en) | 2012-01-10 | 2015-04-30 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| CA2865519C (en) | 2012-02-27 | 2018-01-02 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions comprising a solid dispersion of n-[2,4-bis(1,1-dimethylethyl0-5-hydroxyphenyl-1]-1,4-dihydro-4-oxoquinolone-3-carboxamide for treating cystic fibrosis |
| CN103285373A (zh) * | 2013-05-30 | 2013-09-11 | 苏州普罗达生物科技有限公司 | 肿瘤坏死因子-α多肽抑制剂制备及其应用 |
| CN103254291B (zh) * | 2013-05-30 | 2014-06-25 | 常州亚当生物技术有限公司 | 肿瘤坏死因子-α多肽抑制剂及其应用 |
| SG10201704327RA (en) * | 2013-10-14 | 2017-06-29 | Eisai R&D Man Co Ltd | Selectively substituted quinoline compounds |
| CN107250113B (zh) | 2014-10-07 | 2019-03-29 | 弗特克斯药品有限公司 | 囊性纤维化跨膜传导调节蛋白的调节剂的共晶 |
| RU2624906C2 (ru) * | 2015-12-22 | 2017-07-10 | федеральное государственное бюджетное учреждение "Федеральный научно-исследовательский центр эпидемиологии и микробиологии имени почетного академика Н.Ф. Гамалеи" Министерства здравоохранения Российской Федерации | Производные 2-хинальдинкарбоновой кислоты и их противогриппозная активность |
| WO2019053015A1 (en) | 2017-09-13 | 2019-03-21 | Syngenta Participations Ag | MICROBIOCIDE DERIVATIVES OF QUINOLINE (THIO) CARBOXAMIDE |
| CN107812006A (zh) * | 2017-11-13 | 2018-03-20 | 全椒先奇医药科技有限公司 | 一种治疗急性肾衰药物组合物及其应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0498722A1 (fr) * | 1991-02-07 | 1992-08-12 | Roussel Uclaf | Dérivés bicycliques azotés, leur procédé de préparation, les intermédiaires obtenus, leur application comme médicaments et les compositions pharmaceutiques les renfermant |
| WO1994022852A1 (en) * | 1993-03-31 | 1994-10-13 | Syntex (U.S.A.) Inc. | Quinolines as type iv phosphodiesterase inhibitors |
| WO1995003051A1 (en) * | 1993-07-26 | 1995-02-02 | Pharmacia Ab | Use of quinoline-3-carboxamide compounds for inhibiting the production of tumour necrosis factor (tnf) and/or for the treatment of septic shock |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2517229A1 (de) * | 1975-04-18 | 1976-10-28 | Boehringer Mannheim Gmbh | Phenylalkylcarbonsaeure-derivate und verfahren zu ihrer herstellung |
| US4186201A (en) * | 1977-02-07 | 1980-01-29 | Riker Laboratories, Inc. | Methods of using 8(tetrazol-5-ylcarbamoyl)isoquinoline compounds |
| US4147694A (en) * | 1977-02-07 | 1979-04-03 | Riker Laboratories, Inc. | 8-(1H-Tetrazol-5-yl-carbamoyl)quinoline compounds |
| JPH068292B2 (ja) * | 1985-05-07 | 1994-02-02 | アルカロイダ ベギエスゼティ ギャル | トリアゾリルキノリン誘導体 |
-
1997
- 1997-05-20 IL IL12655797A patent/IL126557A/en not_active IP Right Cessation
- 1997-05-20 NZ NZ332341A patent/NZ332341A/xx unknown
- 1997-05-20 SK SK1605-98A patent/SK283162B6/sk unknown
- 1997-05-20 EP EP97923191A patent/EP0952832B1/en not_active Expired - Lifetime
- 1997-05-20 TR TR1998/02385T patent/TR199802385T2/xx unknown
- 1997-05-20 AU AU29058/97A patent/AU722472B2/en not_active Ceased
- 1997-05-20 US US08/859,508 patent/US5804588A/en not_active Expired - Fee Related
- 1997-05-20 RU RU98123074/04A patent/RU2170730C2/ru not_active IP Right Cessation
- 1997-05-20 CA CA002252531A patent/CA2252531A1/en not_active Abandoned
- 1997-05-20 AT AT97923191T patent/ATE406163T1/de not_active IP Right Cessation
- 1997-05-20 PL PL97329922A patent/PL329922A1/xx unknown
- 1997-05-20 CN CNB97194735XA patent/CN1148189C/zh not_active Expired - Fee Related
- 1997-05-20 KR KR1019980709279A patent/KR20000065219A/ko not_active Ceased
- 1997-05-20 BR BR9709015A patent/BR9709015A/pt not_active IP Right Cessation
- 1997-05-20 WO PCT/GB1997/001359 patent/WO1997044036A1/en not_active Ceased
- 1997-05-20 DE DE69738949T patent/DE69738949D1/de not_active Expired - Fee Related
- 1997-05-20 JP JP09541788A patent/JP2000510865A/ja active Pending
- 1997-05-20 CZ CZ0365198A patent/CZ296163B6/cs not_active IP Right Cessation
-
1998
- 1998-11-19 NO NO19985376A patent/NO312099B1/no unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0498722A1 (fr) * | 1991-02-07 | 1992-08-12 | Roussel Uclaf | Dérivés bicycliques azotés, leur procédé de préparation, les intermédiaires obtenus, leur application comme médicaments et les compositions pharmaceutiques les renfermant |
| WO1994022852A1 (en) * | 1993-03-31 | 1994-10-13 | Syntex (U.S.A.) Inc. | Quinolines as type iv phosphodiesterase inhibitors |
| WO1995003051A1 (en) * | 1993-07-26 | 1995-02-02 | Pharmacia Ab | Use of quinoline-3-carboxamide compounds for inhibiting the production of tumour necrosis factor (tnf) and/or for the treatment of septic shock |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1148189C (zh) | 2004-05-05 |
| IL126557A0 (en) | 1999-08-17 |
| PL329922A1 (en) | 1999-04-26 |
| EP0952832A1 (en) | 1999-11-03 |
| SK283162B6 (sk) | 2003-03-04 |
| BR9709015A (pt) | 1999-08-03 |
| SK160598A3 (en) | 1999-12-10 |
| NZ332341A (en) | 2000-05-26 |
| NO985376L (no) | 1998-11-19 |
| WO1997044036A1 (en) | 1997-11-27 |
| IL126557A (en) | 2002-09-12 |
| CZ365198A3 (cs) | 1999-03-17 |
| CZ296163B6 (cs) | 2006-01-11 |
| CA2252531A1 (en) | 1997-11-27 |
| NO985376D0 (no) | 1998-11-19 |
| CN1219131A (zh) | 1999-06-09 |
| ATE406163T1 (de) | 2008-09-15 |
| NO312099B1 (no) | 2002-03-18 |
| JP2000510865A (ja) | 2000-08-22 |
| TR199802385T2 (xx) | 1999-04-21 |
| KR20000065219A (ko) | 2000-11-06 |
| DE69738949D1 (de) | 2008-10-09 |
| US5804588A (en) | 1998-09-08 |
| EP0952832B1 (en) | 2008-08-27 |
| RU2170730C2 (ru) | 2001-07-20 |
| AU2905897A (en) | 1997-12-09 |
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