TW200306193A - Indolyl-urea derivatives of thienopyridines useful as antiangiogenic agents, and methods for their use - Google Patents
Indolyl-urea derivatives of thienopyridines useful as antiangiogenic agents, and methods for their use Download PDFInfo
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- TW200306193A TW200306193A TW092103808A TW92103808A TW200306193A TW 200306193 A TW200306193 A TW 200306193A TW 092103808 A TW092103808 A TW 092103808A TW 92103808 A TW92103808 A TW 92103808A TW 200306193 A TW200306193 A TW 200306193A
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Classifications
-
- 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
- C07D495/02—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 two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
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|---|---|---|---|
| US36095202P | 2002-03-01 | 2002-03-01 |
Publications (1)
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|---|---|
| TW200306193A true TW200306193A (en) | 2003-11-16 |
Family
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Family Applications (1)
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| TW092103808A TW200306193A (en) | 2002-03-01 | 2003-02-24 | Indolyl-urea derivatives of thienopyridines useful as antiangiogenic agents, and methods for their use |
Country Status (15)
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|---|---|
| US (1) | US6833456B2 (https=) |
| EP (1) | EP1483268A2 (https=) |
| JP (1) | JP2005527511A (https=) |
| AR (1) | AR040398A1 (https=) |
| AU (1) | AU2003206068A1 (https=) |
| BR (1) | BR0308162A (https=) |
| CA (1) | CA2478050A1 (https=) |
| GT (1) | GT200300046A (https=) |
| HN (1) | HN2003000080A (https=) |
| MX (1) | MXPA04008403A (https=) |
| PA (1) | PA8568101A1 (https=) |
| PE (1) | PE20030944A1 (https=) |
| TW (1) | TW200306193A (https=) |
| UY (1) | UY27685A1 (https=) |
| WO (1) | WO2003074529A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116082214A (zh) * | 2023-02-24 | 2023-05-09 | 常州大学 | 一种2-芳基-3-叔丁基吲哚类化合物、制备方法及其应用 |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
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| UA77303C2 (en) | 2002-06-14 | 2006-11-15 | Pfizer | Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use |
| TW200503994A (en) * | 2003-01-24 | 2005-02-01 | Novartis Ag | Organic compounds |
| EA009994B1 (ru) * | 2003-12-23 | 2008-06-30 | Пфайзер Инк. | Новые хинолиновые производные |
| AU2008202205B2 (en) * | 2003-12-23 | 2009-09-10 | Pfizer Inc. | Novel quinoline derivatives |
| WO2005066124A1 (ja) * | 2003-12-26 | 2005-07-21 | Daiichi Pharmaceutical Co., Ltd. | ピロリジン誘導体の製造法 |
| GB0412467D0 (en) * | 2004-06-04 | 2004-07-07 | Astrazeneca Ab | Chemical compounds |
| KR101257343B1 (ko) | 2004-07-30 | 2013-04-23 | 메틸진 인코포레이티드 | Ｖｅｇｆ 수용체 및 ｈｇｆ 수용체 신호전달 억제제 |
| AU2006313456B2 (en) * | 2005-05-20 | 2011-06-23 | Methylgene Inc. | Inhibitors of VEGF receptor and HGF receptor signaling |
| CN101796055B (zh) | 2005-05-20 | 2013-09-04 | 梅特希尔基因公司 | Vegf受体和hgf受体信号的抑制剂 |
| MX2008001838A (es) | 2005-08-08 | 2008-04-09 | Pfizer | Sales y polimorfos de un inhibidor de vegf-r. |
| JP2009526761A (ja) * | 2006-01-30 | 2009-07-23 | アレイ バイオファーマ、インコーポレイテッド | ヘテロ二環式チオフェン化合物および使用の方法 |
| WO2007107005A1 (en) * | 2006-03-22 | 2007-09-27 | Methylgene, Inc. | Inhibitors of protein tyrosine kinase activity |
| JP2009539878A (ja) * | 2006-06-08 | 2009-11-19 | アレイ バイオファーマ、インコーポレイテッド | キノリン化合物および使用方法 |
| BRPI0908573A2 (pt) | 2008-03-05 | 2012-12-25 | Methylgene Inc | inibidores da atividade de proteÍna tirosina quinase |
| KR101126736B1 (ko) * | 2008-11-27 | 2012-04-12 | 주식회사 레고켐 바이오사이언스 | 티로신 키나아제 저해 화합물, 이의 이성질체 또는 이의 약학적으로 허용가능한 염 및 이를 포함하는 약학적 조성물 |
| CA2806701A1 (en) | 2010-07-29 | 2012-02-02 | Bial - Portela & Ca, S.A. | Process for the synthesis of substituted urea compounds |
| MX2014000648A (es) | 2011-07-19 | 2014-09-25 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y sus usos. |
| CA2929742C (en) | 2013-12-04 | 2022-09-20 | Evotec International Gmbh | Sulfoximine substituted quinazolines for pharmaceutical compositions |
| EA201691831A1 (ru) | 2014-04-25 | 2017-02-28 | Пфайзер Инк. | Гетероароматические соединения и их применение в качестве допаминовых d1 лигандов |
| CN115746017B (zh) * | 2022-11-30 | 2024-06-07 | 英维沃化工科技(广州)有限公司 | 一种噻吩并嘧啶类化合物及其制备方法和应用 |
Family Cites Families (31)
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|---|---|---|---|---|
| GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
| US6177401B1 (en) | 1992-11-13 | 2001-01-23 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften | Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis |
| BR9506936A (pt) | 1994-02-23 | 1997-09-09 | Pfizer | Derivados de quinazolina substituídos com 4-heterociclila processos para sua preparaçao e seu uso como agentes anticancerosos |
| US5863949A (en) | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| MX9707453A (es) | 1995-03-30 | 1997-12-31 | Pfizer | Derivados de quinazolina. |
| DK0821671T3 (da) * | 1995-04-20 | 2001-04-23 | Pfizer | Arylsulfonylhydroxamsyrederivater som MMP- og TNF-inhibitorer |
| US5880141A (en) * | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| ATE247469T1 (de) | 1995-06-07 | 2003-09-15 | Pfizer | Heterocyclische kondensierte pyrimidin-derivate |
| AR004010A1 (es) | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
| GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| US6291455B1 (en) | 1996-03-05 | 2001-09-18 | Zeneca Limited | 4-anilinoquinazoline derivatives |
| EP0907642B1 (en) | 1996-06-24 | 2005-11-02 | Pfizer Inc. | Phenylamino-substituted tricyclic derivatives for treatment of hyperproliferative diseases |
| US6071935A (en) * | 1996-06-27 | 2000-06-06 | Pfizer Inc. | Derivatives of 2-(2-oxo-ethylidene)-imidazolidin-4-one and their use as farnesyl protein transferase inhibitors |
| ES2191187T3 (es) | 1996-07-13 | 2003-09-01 | Glaxo Group Ltd | Compuestos heteroaromaticos biciclicos como inhibidores de la proteina tirosin-quinasa. |
| HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| EP0923585B1 (en) | 1996-07-18 | 2002-05-08 | Pfizer Inc. | Phosphinate based inhibitors of matrix metalloproteases |
| WO1998007697A1 (en) | 1996-08-23 | 1998-02-26 | Pfizer Inc. | Arylsulfonylamino hydroxamic acid derivatives |
| US6413971B1 (en) | 1996-11-27 | 2002-07-02 | Pfizer Inc | Fused bicyclic pyrimidine derivatives |
| WO1998030566A1 (en) | 1997-01-06 | 1998-07-16 | Pfizer Inc. | Cyclic sulfone derivatives |
| EP0977733B1 (en) | 1997-02-03 | 2003-09-03 | Pfizer Products Inc. | Arylsulfonylamino hydroxamic acid derivatives |
| JP2000507975A (ja) | 1997-02-07 | 2000-06-27 | ファイザー・インク | Ｎ−ヒドロキシ−β−スルホニルプロピオンアミド誘導体類及びそれらのマトリックスメタロプロテイナーゼ阻害薬としての使用 |
| EA002546B1 (ru) | 1997-02-11 | 2002-06-27 | Пфайзер Инк. | Производные арилсульфонилгидроксамовой кислоты |
| CA2291709A1 (en) | 1997-05-30 | 1998-12-03 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
| WO1999010349A1 (en) | 1997-08-22 | 1999-03-04 | Zeneca Limited | Oxindolylquinazoline derivatives as angiogenesis inhibitors |
| WO1999016755A1 (en) | 1997-09-26 | 1999-04-08 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
| PA8469501A1 (es) | 1998-04-10 | 2000-09-29 | Pfizer Prod Inc | Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico |
| PA8469401A1 (es) | 1998-04-10 | 2000-05-24 | Pfizer Prod Inc | Derivados biciclicos del acido hidroxamico |
| EA005032B1 (ru) | 1998-05-29 | 2004-10-28 | Сьюджен, Инк. | Пирролзамещенные 2-индолиноны (варианты), фармацевтическая композиция (варианты), способ модулирования каталитической активности протеинкиназы, способ лечения или профилактики нарушения в организме, связанного с протеинкиназой |
| BR9916536A (pt) | 1998-12-23 | 2002-01-02 | Searle & Co | Método para o tratamento ou prevenção de um distúrbio de neoplasia em um mamìfero em necessidade deste tratamento ou prevenção, e, combinação |
| JP2003535867A (ja) * | 2000-06-06 | 2003-12-02 | ファイザー プロダクツ インコーポレイテッド | 抗癌剤として有用なチオフェン誘導体 |
| AU2002345792A1 (en) * | 2001-06-21 | 2003-01-08 | Pfizer Inc. | Thienopyridine and thienopyrimidine anticancer agents |
-
2003
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- 2003-02-17 MX MXPA04008403A patent/MXPA04008403A/es active IP Right Grant
- 2003-02-17 WO PCT/IB2003/000740 patent/WO2003074529A2/en not_active Ceased
- 2003-02-17 JP JP2003572997A patent/JP2005527511A/ja not_active Abandoned
- 2003-02-17 EP EP03702952A patent/EP1483268A2/en not_active Withdrawn
- 2003-02-17 AU AU2003206068A patent/AU2003206068A1/en not_active Abandoned
- 2003-02-17 CA CA002478050A patent/CA2478050A1/en not_active Abandoned
- 2003-02-21 US US10/371,337 patent/US6833456B2/en not_active Expired - Fee Related
- 2003-02-24 TW TW092103808A patent/TW200306193A/zh unknown
- 2003-02-26 PE PE2003000186A patent/PE20030944A1/es not_active Application Discontinuation
- 2003-02-27 GT GT200300046A patent/GT200300046A/es unknown
- 2003-02-27 HN HN2003000080A patent/HN2003000080A/es unknown
- 2003-02-27 UY UY27685A patent/UY27685A1/es not_active Application Discontinuation
- 2003-02-27 PA PA20038568101A patent/PA8568101A1/es unknown
- 2003-02-28 AR AR20030100668A patent/AR040398A1/es not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116082214A (zh) * | 2023-02-24 | 2023-05-09 | 常州大学 | 一种2-芳基-3-叔丁基吲哚类化合物、制备方法及其应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2478050A1 (en) | 2003-09-12 |
| EP1483268A2 (en) | 2004-12-08 |
| WO2003074529A2 (en) | 2003-09-12 |
| MXPA04008403A (es) | 2004-11-26 |
| JP2005527511A (ja) | 2005-09-15 |
| HN2003000080A (es) | 2004-05-05 |
| PE20030944A1 (es) | 2003-11-08 |
| BR0308162A (pt) | 2004-12-07 |
| PA8568101A1 (es) | 2003-11-12 |
| AU2003206068A1 (en) | 2003-09-16 |
| AU2003206068A8 (en) | 2003-09-16 |
| WO2003074529A3 (en) | 2003-12-24 |
| GT200300046A (es) | 2003-10-10 |
| UY27685A1 (es) | 2003-10-31 |
| AR040398A1 (es) | 2005-04-06 |
| US20040019065A1 (en) | 2004-01-29 |
| US6833456B2 (en) | 2004-12-21 |
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