JP2000510865A - Ｔｎｆとｐｄｅ―ｉｖのインヒビターとしてのキノリンカルボキサミド - Google Patents
Ｔｎｆとｐｄｅ―ｉｖのインヒビターとしてのキノリンカルボキサミドInfo
- Publication number
- JP2000510865A JP2000510865A JP09541788A JP54178897A JP2000510865A JP 2000510865 A JP2000510865 A JP 2000510865A JP 09541788 A JP09541788 A JP 09541788A JP 54178897 A JP54178897 A JP 54178897A JP 2000510865 A JP2000510865 A JP 2000510865A
- Authority
- JP
- Japan
- Prior art keywords
- carboxamide
- alkyl
- methoxyquinoline
- disease
- heteroaryl
- 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.)
- Pending
Links
- 239000003112 inhibitor Substances 0.000 title description 7
- ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical class C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 184
- -1 heterocyclo Chemical group 0.000 claims abstract description 68
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 37
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 35
- 201000010099 disease Diseases 0.000 claims abstract description 33
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 27
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims abstract description 25
- 125000003118 aryl group Chemical group 0.000 claims abstract description 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 21
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 16
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 15
- 125000005843 halogen group Chemical group 0.000 claims abstract description 14
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 11
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 7
- 125000004001 thioalkyl group Chemical group 0.000 claims abstract description 7
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims abstract description 6
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims abstract description 5
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims abstract description 5
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- 150000003839 salts Chemical class 0.000 claims description 26
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
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- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 4
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- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
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- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
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- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
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- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
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- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
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- 230000000552 rheumatic effect Effects 0.000 claims description 2
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- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 2
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- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- 201000003866 lung sarcoma Diseases 0.000 claims 2
- 230000001105 regulatory effect Effects 0.000 claims 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
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- 238000009825 accumulation Methods 0.000 claims 1
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- 230000000954 anitussive effect Effects 0.000 claims 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 claims 1
- 239000003434 antitussive agent Substances 0.000 claims 1
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- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 abstract 1
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- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
- WVYHWYJCJAGZNB-UHFFFAOYSA-N tert-butyl n-(5-bromo-8-methoxyquinolin-2-yl)carbamate Chemical compound C1=C(NC(=O)OC(C)(C)C)N=C2C(OC)=CC=C(Br)C2=C1 WVYHWYJCJAGZNB-UHFFFAOYSA-N 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
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- YAJRBOPRVQTSMI-UHFFFAOYSA-N trimethyl(tetrazol-1-yl)stannane Chemical compound C[Sn](C)(C)N1C=NN=N1 YAJRBOPRVQTSMI-UHFFFAOYSA-N 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)
- 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 |
| GB9610506.9 | 1996-05-20 | ||
| GBGB9623234.3A GB9623234D0 (en) | 1996-11-07 | 1996-11-07 | Novel compounds |
| GB9623234.3 | 1996-11-07 | ||
| GB9626883.4 | 1996-12-24 | ||
| GBGB9626883.4A GB9626883D0 (en) | 1996-12-24 | 1996-12-24 | Compounds |
| GBGB9708072.5A GB9708072D0 (en) | 1997-04-22 | 1997-04-22 | Compounds |
| GB9708072.5 | 1997-04-22 | ||
| 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 |
|---|---|
| JP2000510865A true JP2000510865A (ja) | 2000-08-22 |
| JP2000510865A5 JP2000510865A5 (cg-RX-API-DMAC7.html) | 2005-01-13 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP09541788A Pending JP2000510865A (ja) | 1996-05-20 | 1997-05-20 | Ｔｎｆとｐｄｅ―ｉｖのインヒビターとしてのキノリンカルボキサミド |
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| EP (1) | EP0952832B1 (cg-RX-API-DMAC7.html) |
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| KR (1) | KR20000065219A (cg-RX-API-DMAC7.html) |
| CN (1) | CN1148189C (cg-RX-API-DMAC7.html) |
| AT (1) | ATE406163T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU722472B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BR9709015A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2252531A1 (cg-RX-API-DMAC7.html) |
| CZ (1) | CZ296163B6 (cg-RX-API-DMAC7.html) |
| DE (1) | DE69738949D1 (cg-RX-API-DMAC7.html) |
| IL (1) | IL126557A (cg-RX-API-DMAC7.html) |
| NO (1) | NO312099B1 (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ332341A (cg-RX-API-DMAC7.html) |
| PL (1) | PL329922A1 (cg-RX-API-DMAC7.html) |
| RU (1) | RU2170730C2 (cg-RX-API-DMAC7.html) |
| SK (1) | SK283162B6 (cg-RX-API-DMAC7.html) |
| TR (1) | TR199802385T2 (cg-RX-API-DMAC7.html) |
| WO (1) | WO1997044036A1 (cg-RX-API-DMAC7.html) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005063293A1 (ja) * | 2003-12-26 | 2005-07-14 | Masatoshi Hagiwara | Sr蛋白質のリン酸化制御方法、および、sr蛋白質の活性制御剤を有効成分とする抗ウイルス剤 |
| JP2007505834A (ja) * | 2003-09-15 | 2007-03-15 | シェーリング コーポレイション | Ｐｄｅｉｖインヒビターの調製のために有用なキノリン５−カルボキサミドの合成 |
| JP2009522353A (ja) * | 2006-01-24 | 2009-06-11 | ユニバーシティ オブ ソウル ファンデーション オブ インダストリアル アンド アカデミック コーポレーション | ＨＩＦ−１α活性剤 |
| JP2010514842A (ja) * | 2007-01-03 | 2010-05-06 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｒｈｏキナーゼインヒビター |
| JP2016535003A (ja) * | 2013-10-14 | 2016-11-10 | 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 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0876345B1 (en) * | 1995-10-16 | 2004-08-18 | Fujisawa Pharmaceutical Co., Ltd. | Heterocyclic compounds as h+-atpases |
| GB9712761D0 (en) * | 1997-06-17 | 1997-08-20 | Chiroscience Ltd | Quinolines and their therapeutic use |
| GB9824160D0 (en) * | 1998-11-04 | 1998-12-30 | Darwin Discovery Ltd | Heterocyclic compounds and their therapeutic use |
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| 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 |
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| SE0200920D0 (sv) * | 2002-03-25 | 2002-03-25 | Astrazeneca Ab | Novel compounds |
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| 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 |
| 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. |
| AU2008228067B2 (en) * | 2007-03-22 | 2011-12-08 | Astrazeneca Ab | Quinoline derivatives for the treatment of inflammatory diseases |
| 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 |
| SI2408750T1 (sl) | 2009-03-20 | 2015-11-30 | Vertex Pharmaceuticals Incorporated | Postopek za izdelavo modulatorjev cistično-fibroznega transmembranskega regulatorja prevodnosti |
| JP2011042643A (ja) * | 2009-07-24 | 2011-03-03 | Bayer Cropscience Ag | 殺虫性カルボキサミド類 |
| EP2569285A1 (en) | 2010-05-10 | 2013-03-20 | Gilead Sciences, Inc. | Bifunctional quinoline derivatives |
| WO2011143106A1 (en) | 2010-05-10 | 2011-11-17 | Gilead Sciences, Inc. | Bi - functional pyrazolopyridine compounds |
| WO2013074059A2 (en) * | 2010-11-05 | 2013-05-23 | 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 |
| WO2013106547A1 (en) | 2012-01-10 | 2013-07-18 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| HK1203840A1 (en) | 2012-02-27 | 2015-11-06 | 沃泰克斯药物股份有限公司 | Pharmaceutical composition and administration thereof |
| 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 |
| JP6746569B2 (ja) | 2014-10-07 | 2020-08-26 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | 嚢胞性線維症膜貫通コンダクタンス制御因子のモジュレーターの共結晶 |
| 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 |
| BR112020004982A2 (pt) | 2017-09-13 | 2020-09-15 | Syngenta Participations Ag | derivados microbiocidas de (tio)carboxamida de quinolina |
| 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 |
Family Cites Families (7)
| 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 |
| US4147694A (en) * | 1977-02-07 | 1979-04-03 | Riker Laboratories, Inc. | 8-(1H-Tetrazol-5-yl-carbamoyl)quinoline compounds |
| US4186201A (en) * | 1977-02-07 | 1980-01-29 | Riker Laboratories, Inc. | Methods of using 8(tetrazol-5-ylcarbamoyl)isoquinoline compounds |
| WO1986006721A1 (en) * | 1985-05-07 | 1986-11-20 | Alkaloida Vegyészeti Gyár | Triazolyl quinoline derivatives |
| ATE156120T1 (de) * | 1991-02-07 | 1997-08-15 | Roussel Uclaf | Bizyklische stickstoffverbindungen, ihre herstellung, erhaltene zwischenprodukte, ihre verwendung als arzneimittel und diese enthaltende pharmazeutische zusammensetzungen |
| US5455252A (en) * | 1993-03-31 | 1995-10-03 | Syntex (U.S.A.) Inc. | Optionally substituted 6,8-quinolines |
| SE9302490D0 (sv) * | 1993-07-26 | 1993-07-26 | Kabi Pharmacia Ab | New use of old drugs |
-
1997
- 1997-05-20 TR TR1998/02385T patent/TR199802385T2/xx unknown
- 1997-05-20 AT AT97923191T patent/ATE406163T1/de not_active IP Right Cessation
- 1997-05-20 WO PCT/GB1997/001359 patent/WO1997044036A1/en not_active Ceased
- 1997-05-20 JP JP09541788A patent/JP2000510865A/ja active Pending
- 1997-05-20 DE DE69738949T patent/DE69738949D1/de not_active Expired - Fee Related
- 1997-05-20 CA CA002252531A patent/CA2252531A1/en not_active Abandoned
- 1997-05-20 CN CNB97194735XA patent/CN1148189C/zh not_active Expired - Fee Related
- 1997-05-20 IL IL12655797A patent/IL126557A/en not_active IP Right Cessation
- 1997-05-20 KR KR1019980709279A patent/KR20000065219A/ko not_active Ceased
- 1997-05-20 NZ NZ332341A patent/NZ332341A/xx unknown
- 1997-05-20 CZ CZ0365198A patent/CZ296163B6/cs not_active IP Right Cessation
- 1997-05-20 PL PL97329922A patent/PL329922A1/xx unknown
- 1997-05-20 EP EP97923191A patent/EP0952832B1/en not_active Expired - Lifetime
- 1997-05-20 BR BR9709015A patent/BR9709015A/pt not_active IP Right Cessation
- 1997-05-20 AU AU29058/97A patent/AU722472B2/en not_active Ceased
- 1997-05-20 SK SK1605-98A patent/SK283162B6/sk unknown
- 1997-05-20 RU RU98123074/04A patent/RU2170730C2/ru not_active IP Right Cessation
- 1997-05-20 US US08/859,508 patent/US5804588A/en not_active Expired - Fee Related
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007505834A (ja) * | 2003-09-15 | 2007-03-15 | シェーリング コーポレイション | Ｐｄｅｉｖインヒビターの調製のために有用なキノリン５−カルボキサミドの合成 |
| WO2005063293A1 (ja) * | 2003-12-26 | 2005-07-14 | Masatoshi Hagiwara | Sr蛋白質のリン酸化制御方法、および、sr蛋白質の活性制御剤を有効成分とする抗ウイルス剤 |
| JPWO2005063293A1 (ja) * | 2003-12-26 | 2007-07-19 | 正敏 萩原 | Ｓｒ蛋白質のリン酸化制御方法、および、ｓｒ蛋白質の活性制御剤を有効成分とする抗ウイルス剤 |
| US7569536B2 (en) | 2003-12-26 | 2009-08-04 | Masatoshi Hagiwara | Method for controlling SR protein phosphorylation, and antiviral agents whose active ingredients comprise agents that control SR protein activity |
| JP4771468B2 (ja) * | 2003-12-26 | 2011-09-14 | 正敏 萩原 | Ｓｒ蛋白質のリン酸化制御方法、および、ｓｒ蛋白質の活性制御剤を有効成分とする抗ウイルス剤 |
| US8338362B2 (en) | 2003-12-26 | 2012-12-25 | Masatoshi Hagiwara | Methods for controlling SR protein phosphorylation, and antiviral agents whose active ingredients comprise agents that control SR protein activity |
| US8816089B2 (en) | 2003-12-26 | 2014-08-26 | Masatoshi Hagiwara | Methods for controlling SR protein phosphorylation, and antiviral agents whose active ingredients comprise agents that control SR protein activity |
| JP2009522353A (ja) * | 2006-01-24 | 2009-06-11 | ユニバーシティ オブ ソウル ファンデーション オブ インダストリアル アンド アカデミック コーポレーション | ＨＩＦ−１α活性剤 |
| JP2010514842A (ja) * | 2007-01-03 | 2010-05-06 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｒｈｏキナーゼインヒビター |
| JP2016535003A (ja) * | 2013-10-14 | 2016-11-10 | 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 |
| JP2017226700A (ja) * | 2013-10-14 | 2017-12-28 | 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 |
| JP2019023220A (ja) * | 2013-10-14 | 2019-02-14 | 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20000065219A (ko) | 2000-11-06 |
| CZ296163B6 (cs) | 2006-01-11 |
| CN1219131A (zh) | 1999-06-09 |
| SK160598A3 (en) | 1999-12-10 |
| ATE406163T1 (de) | 2008-09-15 |
| BR9709015A (pt) | 1999-08-03 |
| EP0952832A1 (en) | 1999-11-03 |
| AU722472B2 (en) | 2000-08-03 |
| US5804588A (en) | 1998-09-08 |
| EP0952832B1 (en) | 2008-08-27 |
| AU2905897A (en) | 1997-12-09 |
| RU2170730C2 (ru) | 2001-07-20 |
| DE69738949D1 (de) | 2008-10-09 |
| SK283162B6 (sk) | 2003-03-04 |
| NO985376L (no) | 1998-11-19 |
| IL126557A0 (en) | 1999-08-17 |
| TR199802385T2 (xx) | 1999-04-21 |
| IL126557A (en) | 2002-09-12 |
| NZ332341A (en) | 2000-05-26 |
| CZ365198A3 (cs) | 1999-03-17 |
| PL329922A1 (en) | 1999-04-26 |
| NO985376D0 (no) | 1998-11-19 |
| WO1997044036A1 (en) | 1997-11-27 |
| CN1148189C (zh) | 2004-05-05 |
| NO312099B1 (no) | 2002-03-18 |
| CA2252531A1 (en) | 1997-11-27 |
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