JP2002514228A - 受容体チロシンキナーゼ阻害剤、特にrafキナーゼ阻害剤としてのベンジリン−1,3−ジヒドロ−インドール−2−オン誘導体 - Google Patents
受容体チロシンキナーゼ阻害剤、特にrafキナーゼ阻害剤としてのベンジリン−1,3−ジヒドロ−インドール−2−オン誘導体Info
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- JP2002514228A JP2002514228A JP51383999A JP51383999A JP2002514228A JP 2002514228 A JP2002514228 A JP 2002514228A JP 51383999 A JP51383999 A JP 51383999A JP 51383999 A JP51383999 A JP 51383999A JP 2002514228 A JP2002514228 A JP 2002514228A
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- aliphatic
- het
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- ACDJUCNRYPFNAS-UHFFFAOYSA-N tetraazanium;tetrachloride;hydrate Chemical compound [NH4+].[NH4+].[NH4+].[NH4+].O.[Cl-].[Cl-].[Cl-].[Cl-] ACDJUCNRYPFNAS-UHFFFAOYSA-N 0.000 description 1
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- CFQJBWKKHCMCGJ-UHFFFAOYSA-N tributyl(pyridin-3-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CN=C1 CFQJBWKKHCMCGJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
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- C07D209/34—Oxygen atoms in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
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- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- 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
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- 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
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- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D471/02—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 two hetero rings
- C07D471/04—Ortho-condensed systems
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| GB9716557.5 | 1997-08-06 | ||
| GBGB9716557.5A GB9716557D0 (en) | 1997-08-06 | 1997-08-06 | Benzylidene-1,3-dihydro-indol-2-one derivatives having anti-cancer activity |
| PCT/EP1998/004844 WO1999010325A1 (en) | 1997-08-06 | 1998-08-04 | Benzylidene-1,3-dihydro-indol-2-one derivatives as receptor tyrosine kinase inhibitors, particularly of raf kinases |
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| JP2002514228A true JP2002514228A (ja) | 2002-05-14 |
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| JP51383999A Ceased JP2002514228A (ja) | 1997-08-06 | 1998-08-04 | 受容体チロシンキナーゼ阻害剤、特にrafキナーゼ阻害剤としてのベンジリン−1,3−ジヒドロ−インドール−2−オン誘導体 |
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Families Citing this family (237)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5880141A (en) | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| CA2222545A1 (en) * | 1995-06-07 | 1996-12-19 | Sugen, Inc. | Quinazolines and pharmaceutical compositions |
| US6316635B1 (en) | 1995-06-07 | 2001-11-13 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
| US6906093B2 (en) | 1995-06-07 | 2005-06-14 | Sugen, Inc. | Indolinone combinatorial libraries and related products and methods for the treatment of disease |
| US6147106A (en) | 1997-08-20 | 2000-11-14 | Sugen, Inc. | Indolinone combinatorial libraries and related products and methods for the treatment of disease |
| US6696448B2 (en) | 1996-06-05 | 2004-02-24 | Sugen, Inc. | 3-(piperazinylbenzylidenyl)-2-indolinone compounds and derivatives as protein tyrosine kinase inhibitors |
| JP4713698B2 (ja) | 1997-03-05 | 2011-06-29 | スージェン, インク. | 疎水性薬剤の処方 |
| AR012634A1 (es) | 1997-05-02 | 2000-11-08 | Sugen Inc | Compuesto basado en quinazolina, composicion famaceutica que lo comprende, metodo para sintetizarlo, su uso, metodos de modulacion de la funcion deserina/treonina proteinaquinasa con dicho compuesto y metodo in vitro para identificar compuestos que modulan dicha funcion |
| US6486185B1 (en) | 1997-05-07 | 2002-11-26 | Sugen, Inc. | 3-heteroarylidene-2-indolinone protein kinase inhibitors |
| US6316429B1 (en) | 1997-05-07 | 2001-11-13 | Sugen, Inc. | Bicyclic protein kinase inhibitors |
| US6316479B1 (en) | 1997-05-19 | 2001-11-13 | Sugen, Inc. | Isoxazole-4-carboxamide compounds active against protein tryosine kinase related disorders |
| US6987113B2 (en) | 1997-06-11 | 2006-01-17 | Sugen, Inc. | Tyrosine kinase inhibitors |
| US6051593A (en) * | 1997-06-20 | 2000-04-18 | Sugen, Inc. | 3-(cycloalkanoheteroarylidenyl)-2- indolinone protein tyrosine kinase inhibitors |
| US6114371A (en) * | 1997-06-20 | 2000-09-05 | Sugen, Inc. | 3-(cyclohexanoheteroarylidenyl)-2-indolinone protein tyrosine kinase inhibitors |
| US6313158B1 (en) | 1997-06-20 | 2001-11-06 | Sugen, Inc. | Bioavailability of 3-heteroarylidenyl-2-indolinones active as protein tyrosine kinase inhibitors |
| US6130238A (en) * | 1997-06-20 | 2000-10-10 | Sugen, Inc. | 3-(cyclohexanoheteroarylidenyl)-2-indolinone protein tyrosine kinase inhibitors |
| US6235769B1 (en) | 1997-07-03 | 2001-05-22 | Sugen, Inc. | Methods of preventing and treating neurological disorders with compounds that modulate the function of the C-RET receptor protein tyrosine kinase |
| US6133305A (en) | 1997-09-26 | 2000-10-17 | Sugen, Inc. | 3-(substituted)-2-indolinones compounds and use thereof as inhibitors of protein kinase activity |
| US6531502B1 (en) | 1998-01-21 | 2003-03-11 | Sugen, Inc. | 3-Methylidenyl-2-indolinone modulators of protein kinase |
| US6514981B1 (en) | 1998-04-02 | 2003-02-04 | Sugen, Inc. | Methods of modulating tyrosine protein kinase function with indolinone compounds |
| US6569868B2 (en) | 1998-04-16 | 2003-05-27 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
| 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 |
| US6153634A (en) | 1998-12-17 | 2000-11-28 | Hoffmann-La Roche Inc. | 4,5-azolo-oxindoles |
| CN1158283C (zh) * | 1998-12-17 | 2004-07-21 | 霍夫曼-拉罗奇有限公司 | 作为蛋白激酶抑制剂的4-和5-吡嗪基羟吲哚 |
| EP1149093A1 (en) | 1998-12-17 | 2001-10-31 | F. Hoffmann-La Roche Ag | 4-aryloxindoles as inhibitors of jnk protein kinases |
| BR9916327A (pt) * | 1998-12-17 | 2001-09-18 | Hoffmann La Roche | Oxindóis de 4-alquenila (e alquinila) como inibidores de cinases dependentes de ciclina, em particular, cdk2 |
| GB9904932D0 (en) * | 1999-03-04 | 1999-04-28 | Glaxo Group Ltd | Composition and method for preventing/reducing the severity of side effects of chemotherapy and/or radiation therapy |
| US7064114B2 (en) | 1999-03-19 | 2006-06-20 | Parker Hughes Institute | Gel-microemulsion formulations |
| US6689806B1 (en) | 1999-03-24 | 2004-02-10 | Sugen, Inc. | Indolinone compounds as kinase inhibitors |
| AU3770000A (en) * | 1999-03-24 | 2000-10-09 | Sugen, Inc. | Indolinone compounds as kinase inhibitors |
| JP2000281588A (ja) * | 1999-03-30 | 2000-10-10 | Sankyo Co Ltd | ガンの予防又は治療薬及びそのスクリーニング方法 |
| EP1173254A2 (en) * | 1999-04-27 | 2002-01-23 | Smithkline Beecham Plc | Novel treatment of neurotraumatic conditions with a raf inhibitor |
| US6417214B1 (en) | 1999-05-04 | 2002-07-09 | Wyeth | 3,3-substituted indoline derivatives |
| US6399593B1 (en) | 1999-05-04 | 2002-06-04 | Wyeth | Cyclic regimens using cyclic urea and cyclic amide derivatives |
| US6462032B1 (en) | 1999-05-04 | 2002-10-08 | Wyeth | Cyclic regimens utilizing indoline derivatives |
| US6391907B1 (en) * | 1999-05-04 | 2002-05-21 | American Home Products Corporation | Indoline derivatives |
| US6407101B1 (en) | 1999-05-04 | 2002-06-18 | American Home Products Corporation | Cyanopyrroles |
| US6358947B1 (en) | 1999-05-04 | 2002-03-19 | American Home Products Corporation | Tetracyclic progesterone receptor modulator compounds and methods |
| US6369056B1 (en) | 1999-05-04 | 2002-04-09 | American Home Products Corporation | Cyclic urea and cyclic amide derivatives |
| US6380235B1 (en) | 1999-05-04 | 2002-04-30 | American Home Products Corporation | Benzimidazolones and analogues |
| US6509334B1 (en) | 1999-05-04 | 2003-01-21 | American Home Products Corporation | Cyclocarbamate derivatives as progesterone receptor modulators |
| US6423699B1 (en) | 1999-05-04 | 2002-07-23 | American Home Products Corporation | Combination therapies using benzimidazolones |
| US6444668B1 (en) | 1999-05-04 | 2002-09-03 | Wyeth | Combination regimens using progesterone receptor modulators |
| US6306851B1 (en) | 1999-05-04 | 2001-10-23 | American Home Products Corporation | Cyclocarbamate and cyclic amide derivatives |
| US6358948B1 (en) | 1999-05-04 | 2002-03-19 | American Home Products Corporation | Quinazolinone and benzoxazine derivatives as progesterone receptor modulators |
| US6380178B1 (en) | 1999-05-04 | 2002-04-30 | American Home Products Corporation | Cyclic regimens using cyclocarbamate and cyclic amide derivatives |
| US6355648B1 (en) | 1999-05-04 | 2002-03-12 | American Home Products Corporation | Thio-oxindole derivatives |
| US6339098B1 (en) | 1999-05-04 | 2002-01-15 | American Home Products Corporation | 2,1-benzisothiazoline 2,2-dioxides |
| US6498154B1 (en) | 1999-05-04 | 2002-12-24 | Wyeth | Cyclic regimens using quinazolinone and benzoxazine derivatives |
| US6319912B1 (en) | 1999-05-04 | 2001-11-20 | American Home Products Corporation | Cyclic regimens using 2,1-benzisothiazoline 2,2-dioxides |
| US6329416B1 (en) | 1999-05-04 | 2001-12-11 | American Home Products Corporation | Combination regimens using 3,3-substituted indoline derivatives |
| US6432979B1 (en) | 1999-08-12 | 2002-08-13 | American Cyanamid Company | Method of treating or inhibiting colonic polyps and colorectal cancer |
| US6878733B1 (en) | 1999-11-24 | 2005-04-12 | Sugen, Inc. | Formulations for pharmaceutical agents ionizable as free acids or free bases |
| US6313310B1 (en) | 1999-12-15 | 2001-11-06 | Hoffmann-La Roche Inc. | 4-and 5-alkynyloxindoles and 4-and 5-alkenyloxindoles |
| EP1255536B1 (en) | 1999-12-22 | 2006-06-28 | Sugen, Inc. | Indolinone derivatives for modulation of c-kit tyrosine protein kinase |
| US6339100B1 (en) * | 1999-12-29 | 2002-01-15 | The Trustees Of Columbia University In The City Of New York | Methods for inhibiting mastocytosis |
| WO2001056557A2 (en) * | 2000-02-05 | 2001-08-09 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of erk |
| SI1255752T1 (sl) | 2000-02-15 | 2007-12-31 | Pharmacia & Upjohn Co Llc | S pirolom substituirani zaviralci 2-indolinon protein kinaza |
| US6620818B1 (en) | 2000-03-01 | 2003-09-16 | Smithkline Beecham Corporation | Method for reducing the severity of side effects of chemotherapy and/or radiation therapy |
| UA73119C2 (en) | 2000-04-19 | 2005-06-15 | American Home Products Corpoir | Derivatives of cyclic thiocarbamates, pharmaceutical composition including noted derivatives of cyclic thiocarbamates and active ingredients of medicines as modulators of progesterone receptors |
| MY128450A (en) | 2000-05-24 | 2007-02-28 | Upjohn Co | 1-(pyrrolidin-1-ylmethyl)-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives |
| JP2003535847A (ja) | 2000-06-02 | 2003-12-02 | スージェン・インコーポレーテッド | 蛋白質キナーゼ/ホスファターゼ阻害剤としてのインドリノン誘導体 |
| GB0016454D0 (en) | 2000-07-04 | 2000-08-23 | Hoffmann La Roche | Thienopyrrolidinones |
| CA2417500C (en) * | 2000-07-28 | 2008-11-18 | Georgetown University Medical Center | Erbb-2 selective small molecule kinase inhibitors |
| ES2230337T3 (es) | 2000-09-01 | 2005-05-01 | Glaxo Group Limited | Derivados de oxindol. |
| US6638965B2 (en) | 2000-11-01 | 2003-10-28 | Boehringer Ingelheim Pharma Kg | Substituted indolinones, preparation thereof and their use as pharmaceutical compositions |
| DE10054019A1 (de) * | 2000-11-01 | 2002-05-23 | Boehringer Ingelheim Pharma | Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| EP1512413A3 (en) | 2001-01-16 | 2009-09-23 | Glaxo Group Limited | Pharmaceutical combination containing a 4-quinazolineamine and another anti-neoplastic agent for the treatment of cancer |
| AR042586A1 (es) | 2001-02-15 | 2005-06-29 | Sugen Inc | 3-(4-amidopirrol-2-ilmetiliden)-2-indolinona como inhibidores de la protein quinasa; sus composiciones farmaceuticas; un metodo para la modulacion de la actividad catalitica de la proteinquinasa; un metodo para tratar o prevenir una afeccion relacionada con la proteinquinasa |
| WO2002070478A1 (en) | 2001-03-06 | 2002-09-12 | Astrazeneca Ab | Indolone derivatives having vascular-damaging activity |
| AU2002303892A1 (en) | 2001-05-30 | 2002-12-09 | Jingrong Cui | 5-aralkylsulfonyl-3- (pyrrol-2-ylmethylidene)-2-indolinone derivatives as kinase inhibitors |
| DE10134196B4 (de) | 2001-07-13 | 2005-08-18 | Forschungszentrum Karlsruhe Gmbh Technik Und Umwelt | Pharmazeutische Zusammensetzung zur Hemmung der unkontrollierten Vermehrung und/oder Induzierung der Apoptose von Zellen |
| ATE343575T1 (de) * | 2001-09-27 | 2006-11-15 | Smithkline Beecham Corp | Azaoxoindol derivate als trk protein kinase hemmstoffe zur behandlung von krebs und chronischem schmerz |
| US20030187026A1 (en) | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
| US20030119839A1 (en) * | 2001-12-13 | 2003-06-26 | Nan-Horng Lin | Protein kinase inhibitors |
| US6797825B2 (en) | 2001-12-13 | 2004-09-28 | Abbott Laboratories | Protein kinase inhibitors |
| GB0206861D0 (en) * | 2002-03-22 | 2002-05-01 | Glaxo Group Ltd | Medicaments |
| US6541504B1 (en) | 2002-04-03 | 2003-04-01 | Allergan Sales, Llc | (3Z)-3-(2,3-dihydro-1H-inden-1-ylidene)-1,3-dihydro-2H-indol-2-ones as kinase inhibitors |
| AU2003221684A1 (en) * | 2002-04-08 | 2003-10-27 | Smithkline Beecham Corporation | Cancer treatment method comprising administering an erb-family inhibitor and a raf and/or ras inhibitor |
| US7514468B2 (en) | 2002-07-23 | 2009-04-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Indolinone derivatives substituted in the 6 position, the preparation thereof and their use as pharmaceutical compositions |
| US7169936B2 (en) | 2002-07-23 | 2007-01-30 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Indolinone derivatives substituted in the 6-position, their preparation and their use as medicaments |
| ITMI20021620A1 (it) * | 2002-07-23 | 2004-01-23 | Novuspharma Spa | Composto ad ativita' antitumorale |
| US7585866B2 (en) * | 2002-07-31 | 2009-09-08 | Critical Outcome Technologies, Inc. | Protein tyrosine kinase inhibitors |
| CA2496164C (en) * | 2002-08-23 | 2010-11-09 | Chiron Corporation | Benzimidazole quinolinones and uses thereof |
| US7825132B2 (en) * | 2002-08-23 | 2010-11-02 | Novartis Vaccines And Diagnostics, Inc. | Inhibition of FGFR3 and treatment of multiple myeloma |
| US8580782B2 (en) | 2002-09-04 | 2013-11-12 | Merck Sharp & Dohme Corp. | Substituted pyrazolo[1,5-a]pyrimidines as cyclin dependent kinase inhibitors |
| PT1537116E (pt) | 2002-09-04 | 2010-09-03 | Schering Corp | Pirazolopirimidinas adequadas para o tratamento de doenças cancerosas |
| US8673924B2 (en) | 2002-09-04 | 2014-03-18 | Merck Sharp & Dohme Corp. | Substituted pyrazolo[1,5-a]pyrimidines as cyclin dependent kinase inhibitors |
| AU2003273675A1 (en) * | 2002-10-09 | 2004-05-04 | Wayne R. Danter | Protein tyrosine kinase inhibitors |
| AU2003290699B2 (en) * | 2002-11-13 | 2009-08-27 | Novartis Vaccines And Diagnostics, Inc. | Methods of treating cancer and related methods |
| WO2004050681A2 (en) * | 2002-11-15 | 2004-06-17 | Exelixis, Inc. | Kinase modulators |
| US20050019366A1 (en) * | 2002-12-31 | 2005-01-27 | Zeldis Jerome B. | Drug-coated stents and methods of use therefor |
| WO2004064733A2 (en) * | 2003-01-15 | 2004-08-05 | Board Of Regents, University Of Texas System | The use of c-raf inhibitors for the treatment of neurodegenerative diseases |
| CA2526594C (en) * | 2003-05-27 | 2011-11-08 | Robert Per Haegerkvist | Use of tyrosine kinase inhibitors to treat diabetes |
| AR045037A1 (es) | 2003-07-10 | 2005-10-12 | Aventis Pharma Sa | Tetrahidro-1h-pirazolo [3,4-c] piridinas sustituidas, composiciones que las contienen y su utilizacion. |
| PT1682126E (pt) * | 2003-10-16 | 2009-10-02 | Novartis Vaccines & Diagnostic | Benzazois substituídos e sua utilização como inibidores da quinase raf |
| CN102225926A (zh) * | 2003-11-07 | 2011-10-26 | 诺华疫苗和诊断公司 | 具有改进药物特性的喹啉酮类化合物的药学上可接受的盐 |
| WO2005068424A1 (en) * | 2004-01-20 | 2005-07-28 | Cell Therapeutics Europe S.R.L. | Indolinone derivatives as receptor tyrosine kinase ihibitors |
| US7875624B2 (en) * | 2004-02-20 | 2011-01-25 | Novartis Vaccines And Diagnostics, Inc. | Modulating and measuring cellular adhesion |
| SG176463A1 (en) | 2005-02-22 | 2011-12-29 | Univ Michigan | Small molecule inhibitors of mdm2 and uses thereof |
| CA2608171C (en) * | 2005-05-13 | 2014-02-04 | Novartis Ag | Use of quinolinone compounds for treating drug resistant cancers |
| MX2007014782A (es) | 2005-05-23 | 2008-02-19 | Novartis Ag | Formas cristalinas y otras formas de las sales de acido lactico de 4-amino-5-fluoro-3-[6-(4-metilpiperazin-1-il)-1h-bencimidazol-2 -il]-1h quinolin-2-ona. |
| PE20070335A1 (es) | 2005-08-30 | 2007-04-21 | Novartis Ag | Benzimidazoles sustituidos y metodos para su preparacion |
| RU2433826C2 (ru) * | 2005-11-29 | 2011-11-20 | Новартис Аг | Композиции хинолинонов |
| US8546404B2 (en) | 2005-12-13 | 2013-10-01 | Merck Sharp & Dohme | Compounds that are ERK inhibitors |
| MX2008010635A (es) | 2006-02-16 | 2008-10-28 | Schering Corp | Derivados de pirrolidina como inhibidores de cinasa regulada por señales extracelulares. |
| EP2046292B1 (en) * | 2006-07-21 | 2010-03-03 | Novartis AG | Formulations for benzimidazolyl pyridyl ethers |
| KR20090071603A (ko) * | 2006-09-19 | 2009-07-01 | 노파르티스 아게 | Raf 억제제에 대한 표적 조절, 효능, 진단 및/또는 예후의 바이오마커 |
| JP5571387B2 (ja) | 2007-01-11 | 2014-08-13 | クリティカル・アウトカム・テクノロジーズ・インコーポレイテッド | 癌の治療のための化合物および方法 |
| KR100799821B1 (ko) * | 2007-02-05 | 2008-01-31 | 동화약품공업주식회사 | 신규한 이마티닙 캠실레이트 및 그의 제조방법 |
| UY30892A1 (es) | 2007-02-07 | 2008-09-02 | Smithkline Beckman Corp | Inhibidores de la actividad akt |
| US20110160130A1 (en) * | 2007-02-16 | 2011-06-30 | Connie Erickson-Miller | Cancer treatment method |
| UY30915A1 (es) | 2007-02-16 | 2008-09-02 | Smithkline Beecham Corp | Método de tratamiento de canceres |
| US20110129550A1 (en) | 2007-02-16 | 2011-06-02 | Connie Erickson-Miller | Cancer treatment method |
| US20100143440A1 (en) * | 2007-04-30 | 2010-06-10 | The Uab Research Foundation | Ul97 inhibitors for treatment of proliferative disorders |
| PE20090717A1 (es) | 2007-05-18 | 2009-07-18 | Smithkline Beecham Corp | Derivados de quinolina como inhibidores de la pi3 quinasa |
| CL2008001626A1 (es) | 2007-06-05 | 2009-06-05 | Takeda Pharmaceuticals Co | Compuestos derivados de heterociclos fusionados, agente farmaceutico que los comprende y su uso en la profilaxis y tratamiento del cancer. |
| EP2181987B9 (en) | 2007-08-23 | 2014-09-03 | Takeda Pharmaceutical Company Limited | 2-Carbonylaminobenzothiazoles and their use for the prophylaxis and treatment of cancer |
| US8344135B2 (en) | 2007-08-29 | 2013-01-01 | Takeda Pharmaceutical Company Limited | Heterocyclic compound and use thereof |
| US8530508B2 (en) * | 2007-10-09 | 2013-09-10 | Glaxosmithkline Llc | Thrombopoietin receptor agonist (TpoRA) kills acute human myeloid leukemia cells |
| EP2235004A4 (en) | 2007-12-21 | 2011-05-04 | Univ Health Network | INDAZOLYL, BENZIMIDAZOLYL, BENZOTRIAZOLYL-SUBSTITUTED INDOLUND DERIVATIVES AS A KINASE-HEMMER FOR CANCER TREATMENT |
| CA2710039C (en) * | 2007-12-26 | 2018-07-03 | Critical Outcome Technologies, Inc. | Semicarbazones, thiosemicarbazones and related compounds and methods for treatment of cancer |
| WO2009105500A1 (en) | 2008-02-21 | 2009-08-27 | Schering Corporation | Compounds that are erk inhibitors |
| EP2318406B1 (en) | 2008-07-17 | 2016-01-27 | Critical Outcome Technologies, Inc. | Thiosemicarbazone inhibitor compounds and cancer treatment methods |
| JP5743897B2 (ja) | 2008-11-20 | 2015-07-01 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニーGlaxoSmithKline LLC | 化合物 |
| US8697874B2 (en) | 2008-12-01 | 2014-04-15 | Takeda Pharmaceutical Company Limited | Heterocyclic compound and use thereof |
| JO3101B1 (ar) | 2008-12-02 | 2017-09-20 | Takeda Pharmaceuticals Co | مشتقات بنزوثيازول كعوامل مضادة للسرطان |
| ES2467108T3 (es) | 2008-12-09 | 2014-06-11 | Gilead Sciences, Inc. | Moduladores de receptores tipo toll |
| US20110288142A1 (en) | 2009-01-30 | 2011-11-24 | Chen Pingyun Y | CRYSTALLINE N--5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide hydrochloride |
| WO2010100127A1 (en) | 2009-03-04 | 2010-09-10 | Novartis Ag | Disubstituted imidazole derivatives as modulators of raf kinase |
| JP5629752B2 (ja) | 2009-04-06 | 2014-11-26 | ユニバーシティ・ヘルス・ネットワークUniversity Health Network | キナーゼインヒビターおよびこれを用いた癌の治療方法 |
| US8410095B2 (en) | 2009-05-20 | 2013-04-02 | Glaxosmithkline Llc | Thiazolopyrimidinone derivatives as PI3 kinase inhibitors |
| PE20121148A1 (es) | 2009-08-17 | 2012-09-07 | Intellikine Llc | Compuestos heterociclicos y usos de los mismos |
| HUE029098T2 (en) | 2009-08-21 | 2017-02-28 | Novartis Ag | To treat lapatinib cancer |
| CN102596969A (zh) | 2009-08-26 | 2012-07-18 | 赛林药物股份有限公司 | 用作蛋白激酶调节剂的稠合喹啉类化合物 |
| US8242260B2 (en) | 2009-08-28 | 2012-08-14 | Novartis Ag | Compounds and compositions as protein kinase inhibitors |
| JO3002B1 (ar) | 2009-08-28 | 2016-09-05 | Irm Llc | مركبات و تركيبات كمثبطات كيناز بروتين |
| NO2477987T3 (https=) | 2009-09-14 | 2018-06-09 | ||
| US8703781B2 (en) | 2009-10-16 | 2014-04-22 | Glaxosmithkline Llc | Pharmaceutical combination of MEK inhibitor and B-RAF inhibitors |
| US8962652B2 (en) | 2009-10-22 | 2015-02-24 | Gilead Sciences, Inc. | Derivatives of purine or deazapurine useful for the treatment of (inter alia) viral infections |
| WO2011057204A2 (en) * | 2009-11-06 | 2011-05-12 | The Johns Hopkins University | Lrrk2-mediated neuronal toxicity |
| US9181238B2 (en) | 2010-02-05 | 2015-11-10 | Novartis Ag | N-(pyridin-2-yl)sulfonamides and compositions thereof as protein kinase inhibitors |
| CA2794153C (en) | 2010-03-25 | 2018-01-02 | Glaxosmithkline Llc | Substituted indoline derivatives as perk inhibitors |
| CA2999435A1 (en) | 2010-04-01 | 2011-10-06 | Critical Outcome Technologies Inc. | Compounds and method for treatment of hiv |
| JP5442906B2 (ja) | 2010-04-06 | 2014-03-19 | ユニバーシティ・ヘルス・ネットワーク | キナーゼインヒビターおよびこれを用いた癌の治療方法 |
| US20130096149A1 (en) | 2010-06-25 | 2013-04-18 | Novartis Ag | Heteroaryl compounds and compositions as protein kinase inhibitors |
| US20130172378A1 (en) | 2010-09-14 | 2013-07-04 | Glaxosmithkline Llc | Combination of BRAF and VEGF Inhibitors |
| JP5719028B2 (ja) | 2010-10-06 | 2015-05-13 | グラクソスミスクライン エルエルシー | Pi3キナーゼ阻害剤としてのベンズイミダゾール誘導体 |
| GB201112607D0 (en) | 2011-07-22 | 2011-09-07 | Glaxo Group Ltd | Novel compounds |
| TWI505828B (zh) | 2010-12-20 | 2015-11-01 | 葛蘭素史克智慧財產(第二)有限公司 | 新穎醫藥組成物 |
| JP6100700B2 (ja) | 2011-01-11 | 2017-03-22 | ノバルティス アーゲー | 組合せ |
| WO2012116237A2 (en) | 2011-02-23 | 2012-08-30 | Intellikine, Llc | Heterocyclic compounds and uses thereof |
| CN108542906A (zh) | 2011-11-11 | 2018-09-18 | 诺华股份有限公司 | 治疗增生性疾病的方法 |
| ES2695099T3 (es) | 2011-11-23 | 2019-01-02 | Array Biopharma Inc | Formulaciones farmacéuticas |
| WO2013113796A1 (en) | 2012-01-31 | 2013-08-08 | Smithkline Beecham (Cork) Limited | Method of treating cancer |
| WO2013143597A1 (en) | 2012-03-29 | 2013-10-03 | Glaxo Group Limited | Demethylase enzymes inhibitors |
| RU2015118647A (ru) | 2012-11-20 | 2017-01-10 | Дженентек, Инк. | Аминопиримидиновые соединения в качестве ингибиторов содержащих т790м мутантных egfr |
| AU2013352369B2 (en) | 2012-11-30 | 2016-07-28 | Novartis Ag. | Novel pharmaceutical composition |
| EP2943199A1 (en) | 2013-01-09 | 2015-11-18 | Glaxosmithkline Intellectual Property (No. 2) Limited | Combination |
| ES2651331T3 (es) | 2013-01-10 | 2018-01-25 | Glaxosmithkline Intellectual Property (No. 2) Limited | Inhibidores de la sintasa de ácidos grasos |
| GB201311910D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel Compounds |
| US9242969B2 (en) | 2013-03-14 | 2016-01-26 | Novartis Ag | Biaryl amide compounds as kinase inhibitors |
| EP2968340A4 (en) | 2013-03-15 | 2016-08-10 | Intellikine Llc | COMBINING KINASE INHIBITORS AND USES THEREOF |
| SG11201509742QA (en) | 2013-06-03 | 2015-12-30 | Novartis Ag | Combinations of an anti-pd-l1 antibody and a mek inhibitor and/or a braf inhibitor |
| WO2014210354A1 (en) | 2013-06-28 | 2014-12-31 | Genentech, Inc. | Azaindazole compounds as inhibitors of t790m containing egfr mutants |
| GB201311891D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| GB201311888D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| ES3063787T3 (en) | 2013-10-01 | 2026-04-20 | Novartis Ag | Composition comprising a 17 a-hydroxylase/c17,20 lyase (cyp17a1) inhibitor and an akt inhibitor |
| JP6355724B2 (ja) | 2013-10-01 | 2018-07-11 | ノバルティス アーゲー | がんを治療するためのアフレセルチブと組み合わせたエンザルタミド |
| WO2015056180A1 (en) | 2013-10-15 | 2015-04-23 | Glaxosmithkline Intellectual Property (No.2) Limited | Indoline derivatives as inhibitors of perk |
| SG11201602882VA (en) | 2013-10-18 | 2016-05-30 | Univ Health Network | Treatment for pancreatic cancer |
| CN106029074A (zh) | 2013-12-12 | 2016-10-12 | 诺华股份有限公司 | 用于治疗癌症的曲美替尼、帕尼单抗和达拉菲尼组合 |
| WO2015128837A1 (en) | 2014-02-26 | 2015-09-03 | Glaxosmithkline Intellectual Property (No.2) Limited | Methods of treating cancer patients responding to ezh2 inhibitor gsk126 |
| EP3116546A1 (en) | 2014-03-12 | 2017-01-18 | Novartis AG | Combination comprising a btk inhibitor and an akt inhibitor |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| WO2016001907A1 (en) | 2014-07-02 | 2016-01-07 | Prendergast Patrick T | Mogroside iv and mogroside v as agonist/stimulator/un-blocking agent for toll-like receptor 4 and adjuvant for use in human/animal vaccine and to stimulate immunity against disease agents. |
| PT3166607T (pt) | 2014-07-11 | 2022-12-07 | Gilead Sciences Inc | Moduladores de receptores de tipo toll para o tratamento do vih |
| UY36294A (es) | 2014-09-12 | 2016-04-29 | Novartis Ag | Compuestos y composiciones como inhibidores de quinasa |
| CA2960436C (en) | 2014-09-16 | 2021-01-05 | Gilead Sciences, Inc. | Solid forms of a toll-like receptor modulator |
| WO2016055935A1 (en) | 2014-10-06 | 2016-04-14 | Glaxosmithkline Intellectual Property (No.2) Limited | Combination of lysine-specific demethylase 1 inhibitor and thrombopoietin agonist |
| WO2016059602A2 (en) | 2014-10-16 | 2016-04-21 | Glaxo Group Limited | Methods of treating cancer and related compositions |
| MA41414A (fr) | 2015-01-28 | 2017-12-05 | Centre Nat Rech Scient | Protéines de liaison agonistes d' icos |
| GB201506871D0 (en) | 2015-04-22 | 2015-06-03 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| WO2017021911A1 (en) | 2015-08-04 | 2017-02-09 | Glaxosmithkline Intellectual Property Development Limited | Combination treatments and uses and methods thereof |
| KR20180036996A (ko) | 2015-08-04 | 2018-04-10 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | 조합 치료 및 그의 용도 및 방법 |
| EP3331917A1 (en) | 2015-08-04 | 2018-06-13 | GlaxoSmithKline Intellectual Property Development Limited | Combination treatments and uses and methods thereof |
| WO2017021912A1 (en) | 2015-08-06 | 2017-02-09 | Glaxosmithkline Intellectual Property Development Limited | Combined tlrs modulators with anti ox40 antibodies |
| EP3331565A1 (en) | 2015-08-06 | 2018-06-13 | GlaxoSmithKline Intellectual Property Development Ltd | Tlr4 agonists and compositions thereof and their use in the treatment of cancer |
| TW201716084A (zh) | 2015-08-06 | 2017-05-16 | 葛蘭素史克智慧財產發展有限公司 | 組合物及其用途與治療 |
| EP3331919A1 (en) | 2015-08-07 | 2018-06-13 | GlaxoSmithKline Intellectual Property Development Limited | Combination therapy comprising anti ctla-4 antibodies |
| EP4015537A1 (en) | 2015-12-01 | 2022-06-22 | GlaxoSmithKline Intellectual Property Development Limited | Combination treatments and uses and methods thereof |
| TWI704154B (zh) | 2015-12-03 | 2020-09-11 | 英商葛蘭素史克智慧財產發展有限公司 | 新穎化合物 |
| WO2017098421A1 (en) | 2015-12-08 | 2017-06-15 | Glaxosmithkline Intellectual Property Development Limited | Benzothiadiazine compounds |
| WO2017153952A1 (en) | 2016-03-10 | 2017-09-14 | Glaxosmithkline Intellectual Property Development Limited | 5-sulfamoyl-2-hydroxybenzamide derivatives |
| SG10201912074PA (en) | 2016-03-18 | 2020-02-27 | Immune Sensor Llc | Cyclic di-nucleotide compounds and methods of use |
| JP2019510802A (ja) | 2016-04-07 | 2019-04-18 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | タンパク質調節物質として有用な複素環アミド |
| HRP20220936T1 (hr) | 2016-04-07 | 2022-10-28 | Glaxosmithkline Intellectual Property Development Limited | Heterociklički amidi korisni kao modulatori proteina |
| JP2019521166A (ja) | 2016-07-20 | 2019-07-25 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | Perk阻害剤としてのイソキノリン誘導体 |
| WO2018025221A1 (en) | 2016-08-04 | 2018-02-08 | Glaxosmithkline Intellectual Property Development Limited | Anti-icos and anti-pd-1 antibody combination therapy |
| WO2018053354A1 (en) | 2016-09-15 | 2018-03-22 | Arvinas, Inc. | Indole derivatives as estrogen receptor degraders |
| AU2017329090B9 (en) | 2016-09-19 | 2019-09-05 | Novartis Ag | Therapeutic combinations comprising a RAF inhibitor and a ERK inhibitor |
| CN117510491A (zh) | 2016-12-23 | 2024-02-06 | 阿尔维纳斯运营股份有限公司 | 用于迅速加速性纤维肉瘤多肽的靶向降解的化合物和方法 |
| MX2019007646A (es) | 2016-12-23 | 2019-09-06 | Arvinas Operations Inc | Moleculas quimericas dirigidas a la proteolisis del egfr y metodos asociados de uso. |
| US20190375847A1 (en) | 2017-02-15 | 2019-12-12 | Glaxosmithkline Intellectual Property Development Limited | Combination treatment for cancer |
| ES2952265T3 (es) | 2017-05-02 | 2023-10-30 | Novartis Ag | Terapia combinada que comprende un inhibidor de Raf y trametinib |
| CN110831582B (zh) | 2017-07-05 | 2023-08-11 | 诺华股份有限公司 | 药物组合物 |
| WO2019021208A1 (en) | 2017-07-27 | 2019-01-31 | Glaxosmithkline Intellectual Property Development Limited | USEFUL INDAZOLE DERIVATIVES AS PERK INHIBITORS |
| UY37866A (es) | 2017-09-07 | 2019-03-29 | Glaxosmithkline Ip Dev Ltd | Nuevos compuestos derivados de benzoimidazol sustituidos que reducen la proteína myc (c-myc) en las células e inhiben la histona acetiltransferasa de p300/cbp. |
| WO2019053617A1 (en) | 2017-09-12 | 2019-03-21 | Glaxosmithkline Intellectual Property Development Limited | CHEMICAL COMPOUNDS |
| CA3077337A1 (en) | 2017-10-05 | 2019-04-11 | Glaxosmithkline Intellectual Property Development Limited | Modulators of stimulator of interferon genes (sting) |
| US20210238172A1 (en) | 2017-10-05 | 2021-08-05 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides useful as protein modulators and methods of using the same |
| WO2019106605A1 (en) | 2017-12-01 | 2019-06-06 | Board Of Regents, The University Of Texas System | Combination treatment for cancer |
| GB201807924D0 (en) | 2018-05-16 | 2018-06-27 | Ctxt Pty Ltd | Compounds |
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| WO2020030570A1 (en) | 2018-08-06 | 2020-02-13 | Glaxosmithkline Intellectual Property Development Limited | Combinations of an ox40 antibody and a tlr4 modulator and uses thereof |
| WO2020029799A1 (en) * | 2018-08-07 | 2020-02-13 | Metagone Biotech Inc. | Ammonium salts of 3-(3,5-dibromo-4-hydroxybenzyliden)-5-indo-1,3-dihydroindol-2-one and uses thereof |
| CN117224541A (zh) * | 2018-09-18 | 2023-12-15 | 北京强新生物科技有限公司 | 肥胖症的治疗 |
| AR117206A1 (es) | 2018-11-30 | 2021-07-21 | Glaxosmithkline Ip Dev Ltd | Derivados de octahidropirrolo[2,1-b][1,3]tiazepin-7-carboxamido útiles en la terapia para el vih y para el tratamiento del cáncer |
| MX2021009189A (es) | 2019-02-01 | 2021-11-12 | Glaxosmithkline Ip Dev Ltd | Belantamab mafodotin en combinación con pembrolizumab para el tratamiento del cáncer. |
| ES3025633T3 (en) | 2019-05-13 | 2025-06-09 | Novartis Ag | New crystalline forms of n-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methvlphenyl)-2(trifluoromethyl)isonicotinamide as raf inhibitors for the treatment of cancer |
| JP2022533194A (ja) | 2019-05-16 | 2022-07-21 | スティングセラ インコーポレイテッド | ベンゾ[b][1,8]ナフチリジン酢酸誘導体および使用方法 |
| US20220227761A1 (en) | 2019-05-16 | 2022-07-21 | Stingthera, Inc. | Oxoacridinyl acetic acid derivatives and methods of use |
| KR20220026585A (ko) | 2019-06-26 | 2022-03-04 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | Il1rap 결합 단백질 |
| GB201910304D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
| GB201910305D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
| WO2021046289A1 (en) | 2019-09-06 | 2021-03-11 | Glaxosmithkline Intellectual Property Development Limited | Dosing regimen for the treatment of cancer with an anti icos agonistic antibody and ipilimumab |
| WO2021043961A1 (en) | 2019-09-06 | 2021-03-11 | Glaxosmithkline Intellectual Property Development Limited | Dosing regimen for the treatment of cancer with an anti icos agonistic antibody and chemotherapy |
| CN114981265B (zh) | 2019-12-18 | 2025-01-03 | Ctxt私人有限公司 | 化合物 |
| EP4096718A1 (en) | 2020-01-28 | 2022-12-07 | GlaxoSmithKline Intellectual Property Development Limited | Combination treatments and uses and methods thereof |
| JP7834721B2 (ja) | 2020-08-28 | 2026-03-24 | アルビナス・オペレーションズ・インコーポレイテッド | 急速進行性線維肉腫タンパク質分解化合物及び関連する使用方法 |
| CN114573453B (zh) * | 2020-12-02 | 2024-12-03 | 荆楚理工学院 | 一种选择性的羧酸酯裂解方法 |
| CN117677398A (zh) | 2021-07-27 | 2024-03-08 | 东丽株式会社 | 用于癌的治疗和/或预防的药品 |
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| EP4584258A1 (en) | 2022-09-07 | 2025-07-16 | Arvinas Operations, Inc. | Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5880141A (en) * | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| GB2306108A (en) | 1995-10-13 | 1997-04-30 | Merck & Co Inc | Treatment of Raf-mediated cancers with imidazole derivatives |
| ATE243034T1 (de) * | 1996-01-17 | 2003-07-15 | Taiho Pharmaceutical Co Ltd | Intimale verdickungsinhibitoren |
| WO1998007695A1 (en) | 1996-08-23 | 1998-02-26 | Sugen, Inc. | Indolinone combinatorial libraries and related products and methods for the treatment of disease |
-
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-
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- 1998-08-04 ES ES98943832T patent/ES2272008T3/es not_active Expired - Lifetime
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- 1998-08-04 PE PE1998000695A patent/PE112699A1/es not_active Application Discontinuation
- 1998-08-04 EP EP98943832A patent/EP1003721B1/en not_active Expired - Lifetime
- 1998-08-04 DE DE69836332T patent/DE69836332T2/de not_active Expired - Fee Related
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- 1998-08-04 AU AU91584/98A patent/AU9158498A/en not_active Abandoned
- 1998-08-04 US US09/446,586 patent/US6268391B1/en not_active Expired - Fee Related
- 1998-08-04 AT AT98943832T patent/ATE344241T1/de not_active IP Right Cessation
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| WO2005080392A1 (ja) * | 2004-02-19 | 2005-09-01 | Takeda Pharmaceutical Company Limited | ピラゾロキノロン誘導体およびその用途 |
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| JP2007528884A (ja) * | 2004-03-12 | 2007-10-18 | 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 | 新規なシクロアルキル含有5−アシルインドリノン、その製法及びその医薬品としての使用 |
| JP2010538091A (ja) * | 2007-09-06 | 2010-12-09 | ボストン バイオメディカル, インコーポレイテッド | キナーゼ阻害剤の組成物ならびに癌およびキナーゼに関連する他の疾患の治療のためのそれらの使用 |
| JP2015129152A (ja) * | 2007-09-06 | 2015-07-16 | ボストン バイオメディカル, インコーポレイテッド | キナーゼ阻害剤の組成物ならびに癌およびキナーゼに関連する他の疾患の治療のためのそれらの使用 |
| JP2016180013A (ja) * | 2007-09-06 | 2016-10-13 | ボストン バイオメディカル, インコーポレイテッド | キナーゼ阻害剤の組成物ならびに癌およびキナーゼに関連する他の疾患の治療のためのそれらの使用 |
| JP2016513656A (ja) * | 2013-03-13 | 2016-05-16 | ボストン バイオメディカル, インコーポレイテッド | がんの処置のための、がん幹細胞経路キナーゼの阻害剤としての3−(アリールまたはヘテロアリール)メチレンインドリン−2−オン誘導体 |
Also Published As
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| EP1003721A1 (en) | 2000-05-31 |
| ES2272008T3 (es) | 2007-04-16 |
| US6268391B1 (en) | 2001-07-31 |
| DE69836332D1 (de) | 2006-12-14 |
| DE69836332T2 (de) | 2007-12-13 |
| ZA987037B (en) | 2000-02-07 |
| GB9716557D0 (en) | 1997-10-08 |
| MA26529A1 (fr) | 2004-12-20 |
| AR016789A1 (es) | 2001-08-01 |
| AU9158498A (en) | 1999-03-16 |
| ATE344241T1 (de) | 2006-11-15 |
| PE112699A1 (es) | 1999-11-16 |
| WO1999010325A1 (en) | 1999-03-04 |
| EP1003721B1 (en) | 2006-11-02 |
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