NO323375B1 - Isomer forbindelse av sammenbundne pyrrolokarbazoler og isoindoliner, farmasoytisk preparat omfattende forbindelsen, samt anvendelse av forbindelsen for fremstilling av et medikament. - Google Patents
Isomer forbindelse av sammenbundne pyrrolokarbazoler og isoindoliner, farmasoytisk preparat omfattende forbindelsen, samt anvendelse av forbindelsen for fremstilling av et medikament. Download PDFInfo
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- NO323375B1 NO323375B1 NO20020809A NO20020809A NO323375B1 NO 323375 B1 NO323375 B1 NO 323375B1 NO 20020809 A NO20020809 A NO 20020809A NO 20020809 A NO20020809 A NO 20020809A NO 323375 B1 NO323375 B1 NO 323375B1
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- carbon atoms
- unsubstituted
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- alkyl
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Classifications
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Endocrinology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Reproductive Health (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pyrrole Compounds (AREA)
- Emulsifying, Dispersing, Foam-Producing Or Wetting Agents (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15036799P | 1999-08-20 | 1999-08-20 | |
| US09/640,825 US6399780B1 (en) | 1999-08-20 | 2000-08-17 | Isomeric fused pyrrolocarbazoles and isoindolones |
| PCT/US2000/022724 WO2001014380A1 (en) | 1999-08-20 | 2000-08-18 | Isomeric fused pyrrolocarbazoles and isoindolones |
Publications (3)
| Publication Number | Publication Date |
|---|---|
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| KR (1) | KR100756686B1 (pt) |
| CN (1) | CN1370173A (pt) |
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| IL (2) | IL148180A0 (pt) |
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| MX (1) | MXPA02001789A (pt) |
| NO (1) | NO323375B1 (pt) |
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| PL (1) | PL354180A1 (pt) |
| PT (1) | PT1206473E (pt) |
| SK (1) | SK286805B6 (pt) |
| TR (1) | TR200200474T2 (pt) |
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Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6399780B1 (en) * | 1999-08-20 | 2002-06-04 | Cephalon, Inc. | Isomeric fused pyrrolocarbazoles and isoindolones |
| US7122679B2 (en) * | 2000-05-09 | 2006-10-17 | Cephalon, Inc. | Multicyclic compounds and the use thereof |
| AR035971A1 (es) | 2001-05-16 | 2004-07-28 | Cephalon Inc | Metodos para el tratamiento y la prevencion del dolor |
| ES2307780T3 (es) * | 2001-09-21 | 2008-12-01 | Smithkline Beecham Corporation | Compuestos quimicos. |
| SE0104140D0 (sv) * | 2001-12-07 | 2001-12-07 | Astrazeneca Ab | Novel Compounds |
| WO2005000194A2 (en) * | 2002-10-08 | 2005-01-06 | Rinat Neuroscience Corp. | Methods for treating post-surgical pain by administering an anti-nerve growth factor antagonist antibody and compositions containing the same |
| BR0315164A (pt) | 2002-10-08 | 2005-08-23 | Rinat Neuroscience Corp | Métodos para tratar dor pós-cirúrgica administrando um antagonista de fator de crescimento nervoso e composições contendo o mesmo |
| UA80447C2 (en) * | 2002-10-08 | 2007-09-25 | Methods for treating pain by administering nerve growth factor antagonist and opioid analgesic | |
| US7569364B2 (en) * | 2002-12-24 | 2009-08-04 | Pfizer Inc. | Anti-NGF antibodies and methods using same |
| US9498530B2 (en) | 2002-12-24 | 2016-11-22 | Rinat Neuroscience Corp. | Methods for treating osteoarthritis pain by administering a nerve growth factor antagonist and compositions containing the same |
| SI1575517T1 (sl) | 2002-12-24 | 2012-06-29 | Rinat Neuroscience Corp | Protitelesa proti ĺ˝iväśnemu rastnemu dejavniku in metode njihove uporabe |
| ATE491444T1 (de) | 2003-02-19 | 2011-01-15 | Rinat Neuroscience Corp | Verfahren zur behandlung von schmerzen durch verabreichung eines nervenwachstumsfaktor- antagonisten und eines nsaid und diese enthaltende zusammensetzung |
| US7169802B2 (en) | 2003-12-23 | 2007-01-30 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| ES2338344T3 (es) * | 2004-04-07 | 2010-05-06 | Rinat Neuroscience Corporation | Procedimiento de tratamiento del dolor de cancer de hueso mediante la administracion de una antagonista del factor de crecimiento neuronal. |
| US20060058250A1 (en) * | 2004-09-10 | 2006-03-16 | Cephalon, Inc. | Methods of treating proliferative skin diseases using carbazole derivatives |
| EP1804818A4 (en) * | 2004-09-17 | 2009-07-22 | Ford Henry Health System | METHODS AND COMPOSITIONS FOR THE USE OF ANGIOGENESIS INHIBITORS IN THE PREVENTION AND / OR CONTROL OF EPILEPSY |
| SI1846394T1 (sl) | 2005-02-04 | 2012-06-29 | Astrazeneca Ab | Pirazolilaminopiridinski derivati uporabni kot kinazni inhibitorji |
| ATE473975T1 (de) * | 2005-02-16 | 2010-07-15 | Astrazeneca Ab | Chemische verbindungen |
| ES2308731T3 (es) * | 2005-02-16 | 2008-12-01 | Astrazeneca Ab | Compuestos quimicos. |
| WO2006123113A2 (en) * | 2005-05-16 | 2006-11-23 | Astrazeneca Ab | Pyrazolylaminopyrimidine derivatives useful as tyrosine kinase inhibitors |
| AU2006307657B2 (en) * | 2005-10-28 | 2010-10-28 | Astrazeneca Ab | 4- (3-aminopyrazole) pyrimidine derivatives for use as tyrosine kinase inhibitors in the treatment of cancer |
| EP2009005A4 (en) | 2006-04-19 | 2010-06-02 | Astellas Pharma Inc | AZOLECARBOXAMIDE DERIVATIVE |
| US20080021013A1 (en) * | 2006-07-21 | 2008-01-24 | Cephalon, Inc. | JAK inhibitors for treatment of myeloproliferative disorders |
| EP2049535A1 (en) * | 2006-08-02 | 2009-04-22 | Takeda Pharmaceutical Company Limited | Alpha-carboline derivatives and methods for preparation thereof |
| US8362066B2 (en) * | 2006-11-17 | 2013-01-29 | Treventis Corporation | Compounds and methods for treating protein folding disorders |
| US8889271B2 (en) | 2006-11-26 | 2014-11-18 | Duksan High Metal Co., Ltd. | Compound containing a 5-membered heterocycle and organic light-emitting diode using same, and terminal for same |
| JP2010524911A (ja) * | 2007-04-18 | 2010-07-22 | アストラゼネカ アクチボラグ | ５−アミノピラゾール−３−イル−３Ｈ−イミダゾ［４，５−ｂ］ピリジン誘導体と癌の治療のためのその使用 |
| UA99459C2 (en) * | 2007-05-04 | 2012-08-27 | Астразенека Аб | 9-(pyrazol-3-yl)- 9h-purine-2-amine and 3-(pyraz0l-3-yl)-3h-imidazo[4,5-b]pyridin-5-amine derivatives and their use for the treatment of cancer |
| WO2008135786A1 (en) * | 2007-05-04 | 2008-11-13 | Astrazeneca Ab | Amino-thiazolyl- pyrimidine derivatives and their use for the treatment of cancer |
| PL2206707T3 (pl) | 2007-10-24 | 2015-01-30 | Astellas Pharma Inc | Związek azolokarboksamidowy lub jego sól |
| US8426673B2 (en) | 2008-01-11 | 2013-04-23 | Astellas Pharma, Inc. | Pathological animal model for pelvic pain syndrome |
| JP2011522870A (ja) * | 2008-06-11 | 2011-08-04 | アストラゼネカ アクチボラグ | 癌および骨髄増殖性障害の処置に有用な三環式２，４−ジアミノ−ｌ，３，５−トリアジン誘導体 |
| CN102227422A (zh) * | 2008-09-30 | 2011-10-26 | 阿斯利康(瑞典)有限公司 | 杂环jak激酶抑制剂 |
| CN103965204B (zh) | 2008-11-19 | 2016-09-07 | 赛福伦公司 | 吲唑并[5,4-a]吡咯并[3,4-c]咔唑化合物的新形式 |
| CN102482279B (zh) * | 2009-03-30 | 2015-08-12 | 德山新勒克斯 | 有机电子装置及其化合物与终端机 |
| ES2665954T3 (es) | 2010-08-19 | 2018-04-30 | Zoetis Belgium S.A. | Anticuerpos anti-NGF y su uso |
| KR101497122B1 (ko) * | 2011-08-09 | 2015-03-06 | 덕산네오룩스 주식회사 | 2개 이상의 오원자 헤테로고리를 포함하는 화합물 및 이를 이용한 유기전기소자, 그 단말 |
| TWI585088B (zh) | 2012-06-04 | 2017-06-01 | 第一三共股份有限公司 | 作爲激酶抑制劑之咪唑并［１，２－ｂ］嗒衍生物 |
| WO2013184871A1 (en) | 2012-06-06 | 2013-12-12 | Zoetis Llc | Caninized anti-ngf antibodies and methods thereof |
| KR101478884B1 (ko) | 2012-12-24 | 2015-01-05 | 충남대학교산학협력단 | 비스인돌일말레이미드계 화합물 및 이의 제조방법 |
| MX2020004536A (es) | 2017-11-23 | 2020-08-03 | Biomed X Gmbh | Derivados de pirimidina como inhibidores del receptor de tropomiosina quinasa (trka). |
| BR112020017701A2 (pt) | 2018-03-12 | 2020-12-29 | Zoetis Services Llc | Anticorpos anti-ngf e métodos dos mesmos |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816450A (en) | 1986-09-15 | 1989-03-28 | Duke University | Inhibition of protein kinase C by long-chain bases |
| US4735939A (en) | 1987-02-27 | 1988-04-05 | The Dow Chemical Company | Insecticidal activity of staurosporine |
| US4923986A (en) | 1987-03-09 | 1990-05-08 | Kyowa Hakko Kogyo Co., Ltd. | Derivatives of physiologically active substance K-252 |
| JPH07113027B2 (ja) | 1987-12-24 | 1995-12-06 | 協和醗酵工業株式会社 | Ｋ−２５２誘導体 |
| FR2631199B1 (fr) | 1988-05-09 | 1991-03-15 | Centre Nat Rech Scient | Reacteur a plasma |
| US5621101A (en) | 1992-07-24 | 1997-04-15 | Cephalon, Inc. | Protein kinase inhibitors for treatment of neurological disorders |
| JP3344586B2 (ja) | 1993-05-28 | 2002-11-11 | セファロン，インコーポレイテッド | インドロカルバゾール誘導体を含有する前立腺病理疾患の治療剤 |
| US5624949A (en) | 1993-12-07 | 1997-04-29 | Eli Lilly And Company | Protein kinase C inhibitors |
| US5545636A (en) | 1993-12-23 | 1996-08-13 | Eli Lilly And Company | Protein kinase C inhibitors |
| DK0817627T3 (da) | 1993-12-23 | 2005-06-06 | Lilly Co Eli | Inhibitorer af proteinkinase C |
| GB9416467D0 (en) * | 1994-08-13 | 1994-10-05 | Wellcome Found | Compounds for use in medicine |
| US5475110A (en) * | 1994-10-14 | 1995-12-12 | Cephalon, Inc. | Fused Pyrrolocarbazoles |
| US5594009A (en) * | 1994-10-14 | 1997-01-14 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| US5591855A (en) * | 1994-10-14 | 1997-01-07 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| US5705511A (en) * | 1994-10-14 | 1998-01-06 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| NZ323571A (en) | 1995-11-20 | 1998-12-23 | Lilly Co Eli | Protein kinase c inhibitor |
| US5808060A (en) * | 1995-12-11 | 1998-09-15 | Cephalon, Inc. | Fused isoindolones |
| US5616724A (en) * | 1996-02-21 | 1997-04-01 | Cephalon, Inc. | Fused pyrrolo[2,3-c]carbazole-6-ones |
| AU710669B2 (en) | 1996-08-22 | 1999-09-23 | Bristol-Myers Squibb Company | Cytotoxic amino sugar and related sugar derivatives of indolopyrrolocarbazoles |
| US6399780B1 (en) * | 1999-08-20 | 2002-06-04 | Cephalon, Inc. | Isomeric fused pyrrolocarbazoles and isoindolones |
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- 2000-08-18 HU HU0202758A patent/HUP0202758A3/hu unknown
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- 2000-08-18 JP JP2001518711A patent/JP4776842B2/ja not_active Expired - Fee Related
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- 2000-08-18 BR BR0013811-8A patent/BR0013811A/pt not_active Application Discontinuation
- 2000-08-18 AT AT00954136T patent/ATE280172T1/de active
- 2000-08-18 SK SK246-2002A patent/SK286805B6/sk not_active IP Right Cessation
- 2000-08-18 WO PCT/US2000/022724 patent/WO2001014380A1/en active IP Right Grant
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