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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- 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
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Classifications
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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
- A61K31/47—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)
- Neurology (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Communicable Diseases (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (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
ID=27451451
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)
Families Citing this family (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| SK287231B6 (sk) * | 1999-08-21 | 2010-04-07 | Nycomed Gmbh | Liečivo zahŕňajúce PDE inhibítor a agonistu beta2 adrenoreceptora |
| AU1053501A (en) * | 1999-11-02 | 2001-05-14 | 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 |
| WO2002012189A1 (en) * | 2000-08-09 | 2002-02-14 | Mitsubishi Pharma Corporation | Fused bicyclic amide compounds and medicinal use 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 |
| MXPA03010679A (es) * | 2001-05-23 | 2004-03-02 | Tanabe Seiyaku Co | Una composicion para acelerar la cicatrizacion de fractura osea. |
| CN1537018A (zh) * | 2001-05-23 | 2004-10-13 | 田边制药株式会社 | 一种用于软骨疾病再生治疗的组合物 |
| DE60215178T2 (de) | 2001-07-16 | 2007-08-23 | Astrazeneca Ab | Quinolin-derivate und ihre verwendung als inhibitoren der tyrosine kinase |
| US7375232B2 (en) * | 2001-08-15 | 2008-05-20 | E.I. Du Pont De Nemours And Company | Ortho-heterocyclic substituted aryl amides for controlling invertebrate pests |
| DK1463493T3 (da) | 2001-12-14 | 2008-02-04 | Serono Lab | Fremgangsmåder til at inducere æglösning ved anvendelse af en ikke polypeptid-cAMP-niveaumodulator |
| 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 |
| WO2004087211A2 (en) | 2003-04-01 | 2004-10-14 | Applied Research Systems Ars Holding N.V. | Inhibitors of phosphodiesterases in infertility |
| TWI324151B (en) * | 2003-04-02 | 2010-05-01 | Novartis Ag | Process for the preparation of 5-(haloacetyl)-8-substituted oxy-(1h)-quinolin-2-ones |
| EP1644041A1 (en) * | 2003-05-29 | 2006-04-12 | AstraZeneca AB | A pharmaceutical composition comprising a p2x7 antagonist and sulfasalazine |
| MXPA05012705A (es) * | 2003-05-29 | 2006-02-08 | Astrazeneca Ab | Una composicion farmaceutica que comprende un antagonista del receptor p2x7 y un factor alfa de necrosis tumoral. |
| US20070281931A1 (en) * | 2003-05-29 | 2007-12-06 | Nigel Boughton-Smith | Pharmaceutical Composition Containing a P2x7 Receptor Antagonist and Methotrexate |
| 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 |
| ATE366728T1 (de) * | 2003-09-15 | 2007-08-15 | Schering Corp | Synthese von für die herstellung von pde-iv- inhibitoren geeigneten chinolin-5-carboxamiden |
| SE0302488D0 (sv) * | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | New combination |
| RU2006124843A (ru) | 2003-12-12 | 2008-01-20 | Уайт (Us) | Хинолины, пригодные для лечения сердечно-сосудистого заболевания |
| KR101122708B1 (ko) * | 2003-12-26 | 2012-03-26 | 마사토시 하기와라 | Ｓｒ 단백질 인산화 제어 방법, 및 유효성분으로서 ｓｒ 단백질 활성 제어제를 함유하는 항바이러스제 |
| CA2555133A1 (en) * | 2004-02-04 | 2005-09-01 | Pfizer Products Inc. | Substituted quinoline compounds |
| US20070191404A1 (en) * | 2004-04-01 | 2007-08-16 | Pierre Bartsch | Pharmaceutical compositions of pyrimidine-2,4,6-triones |
| WO2005116009A1 (en) * | 2004-05-18 | 2005-12-08 | Schering Corporation | Substituted 2-quinolyl-oxazoles useful as pde4 inhibitors |
| 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 |
| CN104788328B (zh) | 2004-06-24 | 2017-09-12 | 沃泰克斯药物股份有限公司 | Atp‑结合弹夹转运蛋白的调控剂 |
| 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 |
| AU2005293196B2 (en) * | 2004-10-12 | 2012-03-22 | Actelion Pharmaceuticals Ltd | 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea as crystalline sulfate salt |
| ES2367515T3 (es) * | 2004-10-19 | 2011-11-04 | F. Hoffmann-La Roche Ag | Derivados de quinolina. |
| SE0402925D0 (sv) * | 2004-11-30 | 2004-11-30 | Astrazeneca Ab | Novel Compounds |
| US8686002B2 (en) | 2005-08-21 | 2014-04-01 | AbbVie Deutschland GmbH & Co. KG | Heterocyclic compounds and their use as binding partners for 5-HT5 receptors |
| EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
| CA2620333A1 (en) | 2005-08-26 | 2007-03-01 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| AU2006304787A1 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by PDE inhibition |
| EP2314289A1 (en) | 2005-10-31 | 2011-04-27 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| EP1979367A2 (en) * | 2005-12-24 | 2008-10-15 | Vertex Pharmaceuticals Incorporated | Quinolin-4-one derivatives as modulators of abc transporters |
| WO2007079139A2 (en) | 2005-12-28 | 2007-07-12 | Vertex Pharmaceuticals, Inc. | 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 |
| EP2021000A2 (en) | 2006-05-09 | 2009-02-11 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| CA2657902A1 (en) * | 2006-07-11 | 2008-01-17 | Schering Corporation | Xinafoate salt of a substituted 5-oxazol-2-yl-quinoline compound |
| JPWO2008026687A1 (ja) | 2006-09-01 | 2010-01-21 | 杏林製薬株式会社 | ピラゾロピリジンカルボキサミド誘導体及びそれらを含有するホスホジエステラーゼ（ｐｄｅ）阻害剤 |
| 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. |
| EP2139879B1 (en) * | 2007-03-22 | 2012-07-11 | AstraZeneca AB | Quinoline derivatives for the treatment of inflammatory diseases |
| US9493419B2 (en) | 2007-08-21 | 2016-11-15 | The Hong Kong Polytechnic University | Quinoline derivatives as anti-cancer agents |
| US9321730B2 (en) | 2007-08-21 | 2016-04-26 | The Hong Kong Polytechnic University | Method of making and administering quinoline derivatives as anti-cancer agents |
| PE20091036A1 (es) | 2007-11-30 | 2009-08-15 | Astrazeneca Ab | Derivado de quinolina como antagonista del receptor p2x7 |
| 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 |
| SG10201504084QA (en) | 2009-03-20 | 2015-06-29 | Vertex Pharma | 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 |
| WO2011143106A1 (en) | 2010-05-10 | 2011-11-17 | Gilead Sciences, Inc. | Bi - functional pyrazolopyridine compounds |
| AU2011253203A1 (en) | 2010-05-10 | 2012-11-22 | Gilead Sciences, Inc. | Bifunctional quinoline derivatives |
| 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 |
| WO2013106547A1 (en) | 2012-01-10 | 2013-07-18 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| CN109966264A (zh) | 2012-02-27 | 2019-07-05 | 沃泰克斯药物股份有限公司 | 药物组合物及其施用 |
| 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 |
| JP6223563B2 (ja) * | 2013-10-14 | 2017-11-01 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 選択的に置換されたキノリン化合物 |
| US9701639B2 (en) | 2014-10-07 | 2017-07-11 | Vertex Pharmaceuticals Incorporated | Co-crystals of modulators of cystic fibrosis transmembrane conductance regulator |
| 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 |
| US11266146B2 (en) | 2017-09-13 | 2022-03-08 | Syngenta Participations Ag | Microbiocidal quinoline (thio)carboxamide derivatives |
| 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 |
| BR8606663A (pt) * | 1985-05-07 | 1987-08-11 | Alkaloida Vegyeszeti Gyar | Derivados de triazolil-quinolina |
-
1997
- 1997-05-20 DE DE69738949T patent/DE69738949D1/de not_active Expired - Fee Related
- 1997-05-20 WO PCT/GB1997/001359 patent/WO1997044036A1/en not_active Ceased
- 1997-05-20 BR BR9709015A patent/BR9709015A/pt not_active IP Right Cessation
- 1997-05-20 PL PL97329922A patent/PL329922A1/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 SK SK1605-98A patent/SK283162B6/sk unknown
- 1997-05-20 IL IL12655797A patent/IL126557A/en not_active IP Right Cessation
- 1997-05-20 CZ CZ0365198A patent/CZ296163B6/cs not_active IP Right Cessation
- 1997-05-20 AT AT97923191T patent/ATE406163T1/de not_active IP Right Cessation
- 1997-05-20 TR TR1998/02385T patent/TR199802385T2/xx unknown
- 1997-05-20 JP JP09541788A patent/JP2000510865A/ja active Pending
- 1997-05-20 CN CNB97194735XA patent/CN1148189C/zh 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 NZ NZ332341A patent/NZ332341A/xx unknown
- 1997-05-20 KR KR1019980709279A patent/KR20000065219A/ko not_active Ceased
- 1997-05-20 EP EP97923191A patent/EP0952832B1/en not_active Expired - Lifetime
-
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 |
|---|---|
| DE69738949D1 (de) | 2008-10-09 |
| CN1219131A (zh) | 1999-06-09 |
| CA2252531A1 (en) | 1997-11-27 |
| KR20000065219A (ko) | 2000-11-06 |
| NO985376D0 (no) | 1998-11-19 |
| ATE406163T1 (de) | 2008-09-15 |
| JP2000510865A (ja) | 2000-08-22 |
| EP0952832A1 (en) | 1999-11-03 |
| IL126557A (en) | 2002-09-12 |
| CZ365198A3 (cs) | 1999-03-17 |
| WO1997044036A1 (en) | 1997-11-27 |
| IL126557A0 (en) | 1999-08-17 |
| EP0952832B1 (en) | 2008-08-27 |
| NO312099B1 (no) | 2002-03-18 |
| CZ296163B6 (cs) | 2006-01-11 |
| RU2170730C2 (ru) | 2001-07-20 |
| CN1148189C (zh) | 2004-05-05 |
| TR199802385T2 (xx) | 1999-04-21 |
| BR9709015A (pt) | 1999-08-03 |
| AU2905897A (en) | 1997-12-09 |
| PL329922A1 (en) | 1999-04-26 |
| SK160598A3 (en) | 1999-12-10 |
| SK283162B6 (sk) | 2003-03-04 |
| NO985376L (no) | 1998-11-19 |
| NZ332341A (en) | 2000-05-26 |
| US5804588A (en) | 1998-09-08 |
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| FGA | Letters patent sealed or granted (standard patent) |