CN101857573A - 取代的喹唑啉衍生物及其作为酪氨酸激酶抑制剂的用途 - Google Patents
取代的喹唑啉衍生物及其作为酪氨酸激酶抑制剂的用途 Download PDFInfo
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- CN101857573A CN101857573A CN201010147617A CN201010147617A CN101857573A CN 101857573 A CN101857573 A CN 101857573A CN 201010147617 A CN201010147617 A CN 201010147617A CN 201010147617 A CN201010147617 A CN 201010147617A CN 101857573 A CN101857573 A CN 101857573A
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen 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
- C07D401/12—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
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/93—Sulfur atoms
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- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/112—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C07D295/116—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings with the doubly bound oxygen or sulfur atoms directly attached to a carbocyclic ring
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- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/32—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
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- C07D405/12—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 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D413/02—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
- C07D413/12—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 chain containing hetero atoms as chain links
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| CN98809541A Pending CN1271349A (zh) | 1997-08-01 | 1998-07-29 | 取代的喹唑啉衍生物及其作为酪氨酸激酶抑制剂的用途 |
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Cited By (5)
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| CN113307797A (zh) * | 2020-07-10 | 2021-08-27 | 江南大学 | 一种多取代喹唑啉类化合物及其应用 |
| CN115894455A (zh) * | 2021-09-30 | 2023-04-04 | 北京赛特明强医药科技有限公司 | 一种喹唑啉类化合物、组合物及其应用 |
| CN118834200A (zh) * | 2024-06-27 | 2024-10-25 | 辽宁大学 | 含酰胺结构的4-苯胺基喹唑啉类化合物及其应用 |
Families Citing this family (295)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2174250T5 (es) | 1996-04-12 | 2010-04-21 | Warner-Lambert Company Llc | Inhibidores irreversibles de tirosina quinasas. |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| TW436485B (en) * | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
| WO1999010349A1 (en) | 1997-08-22 | 1999-03-04 | Zeneca Limited | Oxindolylquinazoline derivatives as angiogenesis inhibitors |
| HRP20010119B1 (hr) | 1998-08-18 | 2008-05-31 | The Regents Of The University Of California | Sprječavanje stvaranja sluzi u dišnim putevima primjenom antagonista egf-r |
| US6184226B1 (en) | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| EP1950201A1 (en) | 1998-09-29 | 2008-07-30 | Wyeth Holdings Corporation | Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors |
| ATE294796T1 (de) | 1998-10-08 | 2005-05-15 | Astrazeneca Ab | Chinazolin derivate |
| TR200102505T2 (tr) * | 1999-02-27 | 2003-01-21 | Boehringer Ingelheim Pharma Kg | 4-amino-kinazolin ve kinolin türevleri. |
| DE60009888T2 (de) * | 1999-04-21 | 2005-04-21 | Wyeth Corp | Substituierte 3-cyano-[1.7], [1.5] und [1.8]naphthyridininhibitoren von tyrosin kinasen |
| CA2375259C (en) * | 1999-06-21 | 2009-04-28 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| KR100881105B1 (ko) | 1999-11-05 | 2009-02-02 | 아스트라제네카 아베 | Vegf 억제제로서의 퀴나졸린 유도체 |
| DE60121931T2 (de) | 2000-04-07 | 2007-03-01 | Astrazeneca Ab | Chinazolinverbindungen |
| WO2001077104A1 (de) * | 2000-04-08 | 2001-10-18 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| US6627634B2 (en) | 2000-04-08 | 2003-09-30 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them |
| UA73993C2 (uk) | 2000-06-06 | 2005-10-17 | Астразенека Аб | Хіназолінові похідні для лікування пухлин та фармацевтична композиція |
| EP1299381B1 (en) * | 2000-06-28 | 2008-05-07 | AstraZeneca AB | Substituted quinazoline derivatives and their use as inhibitors |
| AU2001278609B2 (en) | 2000-08-21 | 2005-04-14 | Astrazeneca Ab | Quinazoline derivatives |
| US6617329B2 (en) | 2000-08-26 | 2003-09-09 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines and their use as medicaments |
| DE10042060A1 (de) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE10042062A1 (de) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Hertellung |
| US6656946B2 (en) | 2000-08-26 | 2003-12-02 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
| US6740651B2 (en) | 2000-08-26 | 2004-05-25 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
| US6653305B2 (en) | 2000-08-26 | 2003-11-25 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them |
| US6403580B1 (en) | 2000-08-26 | 2002-06-11 | Boehringer Ingelheim Pharma Kg | Quinazolines, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| JP2004511480A (ja) | 2000-10-13 | 2004-04-15 | アストラゼネカ アクチボラグ | キナゾリン誘導体 |
| JP2004511479A (ja) | 2000-10-13 | 2004-04-15 | アストラゼネカ アクチボラグ | キナゾリン誘導体 |
| US7019012B2 (en) | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
| US6562319B2 (en) | 2001-03-12 | 2003-05-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Radiolabeled irreversible inhibitors of epidermal growth factor receptor tyrosine kinase and their use in radioimaging and radiotherapy |
| WO2002085895A1 (en) | 2001-04-19 | 2002-10-31 | Astrazeneca Ab | Quinazoline derivatives |
| US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| US20040044014A1 (en) | 2002-04-19 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof |
| DE10217689A1 (de) * | 2002-04-19 | 2003-11-13 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, ihre Verwendung und Verfahren zu ihrer Herstellung |
| DE10221018A1 (de) | 2002-05-11 | 2003-11-27 | Boehringer Ingelheim Pharma | Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie |
| DE10230751A1 (de) * | 2002-07-09 | 2004-01-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Arzneimittelkompositionen auf der Basis neuer Anticholinergika und EGFR-Kinase-Hemmern |
| WO2004008099A2 (en) | 2002-07-15 | 2004-01-22 | Genentech, Inc. | METHODS FOR IDENTIFYING TUMORS THAT ARE RESPONSIVE TO TREATMENT WITH ANTI-ErbB2 ANTIBODIES |
| CA2494061C (en) | 2002-07-31 | 2011-06-14 | Wayne R. Danter | Protein tyrosine kinase inhibitors |
| EP2298805A3 (en) | 2002-09-27 | 2011-04-13 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
| WO2004033446A1 (en) | 2002-10-09 | 2004-04-22 | Danter Wayne R | Protein tyrosine kinase inhibitors |
| WO2004056807A1 (en) | 2002-12-20 | 2004-07-08 | Pfizer Products Inc. | Pyrimidine derivatives for the treatment of abnormal cell growth |
| US7109337B2 (en) | 2002-12-20 | 2006-09-19 | Pfizer Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| WO2004064718A2 (en) * | 2003-01-23 | 2004-08-05 | T.K. Signal Ltd. | Irreversible inhibitors of egf receptor tyrosine kinases and uses thereof |
| US7223749B2 (en) | 2003-02-20 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| US20090010920A1 (en) | 2003-03-03 | 2009-01-08 | Xencor, Inc. | Fc Variants Having Decreased Affinity for FcyRIIb |
| GB0309850D0 (en) | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
| EP1633870B1 (en) | 2003-05-30 | 2013-03-27 | OncoTherapy Science, Inc. | Process for screening a drug response in cancer patients |
| BRPI0411126A (pt) * | 2003-06-10 | 2006-07-18 | Hoffmann La Roche | derivados de 1,3,4-triaza-fenaleno e 1,3,4,6-tetraazafenaleno |
| US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
| WO2006074147A2 (en) | 2005-01-03 | 2006-07-13 | Myriad Genetics, Inc. | Nitrogen containing bicyclic compounds and therapeutical use thereof |
| CN1984660B (zh) | 2003-07-03 | 2010-12-15 | 美瑞德生物工程公司 | 作为天冬氨酸特异性半胱氨酸蛋白酶活化剂和细胞程序死亡诱导剂的4-芳基氨基-喹唑啉 |
| JP4828421B2 (ja) | 2003-08-14 | 2011-11-30 | アレイ バイオファーマ、インコーポレイテッド | 受容体チロシンキナーゼ阻害剤としてのキナゾリン誘導体 |
| US7501427B2 (en) | 2003-08-14 | 2009-03-10 | Array Biopharma, Inc. | Quinazoline analogs as receptor tyrosine kinase inhibitors |
| CA2538633A1 (en) * | 2003-09-11 | 2005-03-17 | Yissum Research Development Company Of The Hebrew University Of Jerusale M | Radiolabeled anilinoquinazolines and their use in radioimaging and radiotherapy |
| US9714282B2 (en) | 2003-09-26 | 2017-07-25 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
| US7456189B2 (en) | 2003-09-30 | 2008-11-25 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
| DE10349113A1 (de) | 2003-10-17 | 2005-05-12 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Aminocrotonylverbindungen |
| BR122018071808B8 (pt) | 2003-11-06 | 2020-06-30 | Seattle Genetics Inc | conjugado |
| GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| CN1960731B (zh) * | 2004-02-20 | 2011-12-07 | 诺华疫苗和诊断公司 | 调节炎性和转移过程的方法 |
| EP1733056B1 (en) | 2004-03-31 | 2013-05-22 | The General Hospital Corporation | Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments |
| US7456176B2 (en) | 2004-04-08 | 2008-11-25 | Targegen, Inc. | Benzotriazine inhibitors of kinases |
| SI1746999T1 (sl) | 2004-05-06 | 2012-01-31 | Warner Lambert Co | 4-fenilamino-kinazolin-6-il-amidi |
| MXPA06013164A (es) | 2004-05-14 | 2007-02-13 | Pfizer Prod Inc | Derivados de pirimidina para el tratamiento de crecimiento de celulas anormal. |
| CA2564199A1 (en) | 2004-05-14 | 2005-11-24 | Pfizer Products Inc. | Pyrimidine derivatives for the treatment of abnormal cell growth |
| WO2005111024A1 (en) | 2004-05-14 | 2005-11-24 | Pfizer Products Inc. | Pyrimidine derivatives for the treatment of abnormal cell growth |
| BRPI0510883B8 (pt) | 2004-06-01 | 2021-05-25 | Genentech Inc | composto conjugado de droga e anticorpo, composição farmacêutica, método de fabricação de composto conjugado de droga e anticorpo e usos de uma formulação, de um conjugado de droga e anticorpo e um agente quimioterapêutico e de uma combinação |
| JP2008505174A (ja) | 2004-07-15 | 2008-02-21 | ゼンコー・インコーポレイテッド | 最適化Fc変異体 |
| CN101065151B (zh) | 2004-09-23 | 2014-12-10 | 健泰科生物技术公司 | 半胱氨酸改造的抗体和偶联物 |
| US20070054916A1 (en) * | 2004-10-01 | 2007-03-08 | Amgen Inc. | Aryl nitrogen-containing bicyclic compounds and methods of use |
| JO3000B1 (ar) | 2004-10-20 | 2016-09-05 | Genentech Inc | مركبات أجسام مضادة . |
| US8367805B2 (en) | 2004-11-12 | 2013-02-05 | Xencor, Inc. | Fc variants with altered binding to FcRn |
| EP2325206B1 (en) | 2004-11-12 | 2014-03-19 | Xencor, Inc. | Fc variants with altered binding to fcrn |
| US7947676B2 (en) | 2004-12-14 | 2011-05-24 | Astrazeneca Ab | Pyrazolo[3,4-d]pyrimidine compounds as antitumor agents |
| KR100735639B1 (ko) | 2004-12-29 | 2007-07-04 | 한미약품 주식회사 | 암세포 성장 억제 효과를 갖는 퀴나졸린 유도체 및 이의제조방법 |
| US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
| TWI441646B (zh) | 2005-01-21 | 2014-06-21 | Genentech Inc | 帕妥珠單抗(pertuzumab)用於製備治療人類病患癌症之藥物的用途 |
| CA2596133C (en) | 2005-02-23 | 2016-11-15 | Genentech, Inc. | Extending time to disease progression or survival in cancer patients |
| NZ562223A (en) | 2005-04-19 | 2010-01-29 | Smithkline Beecham Cork Ltd | Pharmaceutical composition comprising lapatinib or N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]4-quinazolinamine |
| CA2652434A1 (en) | 2005-07-08 | 2007-01-18 | Xencor, Inc. | Optimized proteins that target ep-cam |
| DE602006018331D1 (de) | 2005-09-20 | 2010-12-30 | Astrazeneca Ab | 4-(1h-indazol-5-ylamino)chinazolinverbindungen als inhibitoren der erbb-rezeptortyrosinkinase zur behandlung von krebs |
| DK1931709T3 (en) | 2005-10-03 | 2017-03-13 | Xencor Inc | FC VARIETIES WITH OPTIMIZED FC RECEPTOR BINDING PROPERTIES |
| NZ592990A (en) | 2005-11-01 | 2013-01-25 | Targegen Inc | Bi-aryl meta-pyrimidine inhibitors of kinases |
| CA2833852C (en) | 2005-11-11 | 2014-10-21 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
| CN101448778A (zh) * | 2006-05-26 | 2009-06-03 | 艾博特公司 | Polo样激酶的抑制剂 |
| RS53263B (sr) | 2006-08-14 | 2014-08-29 | Xencor Inc. | Optimizovana antitela usmerena na cd19 |
| US20100008910A1 (en) | 2006-09-12 | 2010-01-14 | John Chant | Methods and compositions for the diagnosis and treatment of cancer |
| US8877764B2 (en) | 2006-09-18 | 2014-11-04 | Boehringer Ingelheim International Gmbh | Method for treating cancer harboring EGFR mutations |
| EP1921070A1 (de) | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
| EA200901041A1 (ru) | 2007-02-06 | 2010-02-26 | Бёрингер Ингельхайм Интернациональ Гмбх | Бициклические гетероциклы, содержащие эти соединения лекарственные средства, их применение и способ их получения |
| PL2132573T3 (pl) | 2007-03-02 | 2014-09-30 | Genentech Inc | Prognozowanie odpowiedzi na inhibitor dimeryzacji HER oparte na niskiej ekspresji HER3 |
| LT2176298T (lt) | 2007-05-30 | 2018-04-10 | Xencor, Inc. | Būdai ir kompozicijos, skirti cd32b ekspresuojančių ląstelių slopinimui |
| EP2171090B1 (en) | 2007-06-08 | 2013-04-03 | Genentech, Inc. | Gene expression markers of tumor resistance to her2 inhibitor treatment |
| WO2009045761A1 (en) * | 2007-09-28 | 2009-04-09 | Absolute Science, Inc. | Compounds and methods for treating zinc matrix metalloprotease dependent diseases |
| US8513233B2 (en) | 2007-10-11 | 2013-08-20 | Shanghai Institute Of Materia Medica, Cas | Pyrimidinyl-propionic acid derivatives and their use as PPAR agonists |
| KR101616758B1 (ko) | 2007-12-26 | 2016-04-29 | 젠코어 인코포레이티드 | FcRn에 대한 변경된 결합성을 갖는 Fc 변이체 |
| CA2710039C (en) | 2007-12-26 | 2018-07-03 | Critical Outcome Technologies, Inc. | Semicarbazones, thiosemicarbazones and related compounds and methods for treatment of cancer |
| TWI472339B (zh) | 2008-01-30 | 2015-02-11 | Genentech Inc | 包含結合至her2結構域ii之抗體及其酸性變異體的組合物 |
| PL2245026T3 (pl) | 2008-02-07 | 2013-01-31 | Boehringer Ingelheim Int | Spirocykliczne heterocykle, leki zawierające te związki, ich zastosowanie i sposób ich produkcji |
| US12492253B1 (en) | 2008-02-25 | 2025-12-09 | Xencor, Inc. | Anti-human C5 antibodies |
| ES2444128T3 (es) | 2008-05-13 | 2014-02-24 | Astrazeneca Ab | Nueva SAL-554 |
| CA2723984A1 (en) | 2008-05-14 | 2009-11-19 | Genomic Health Inc. | Predictors of patient response to treatment with egf receptor inhibitors |
| WO2010006438A1 (en) | 2008-07-17 | 2010-01-21 | Critical Outcome Technologies Inc. | Thiosemicarbazone inhibitor compounds and cancer treatment methods |
| JP5539351B2 (ja) | 2008-08-08 | 2014-07-02 | 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 | シクロヘキシルオキシ置換ヘテロ環、これらの化合物を含有する医薬、およびそれらを生成するための方法 |
| ITMI20082336A1 (it) * | 2008-12-29 | 2010-06-30 | Univ Parma | Composti inibitori irreversibili di egfr con attivita' antiproliferativa |
| WO2010104406A1 (en) * | 2009-03-11 | 2010-09-16 | Auckland Uniservices Limited | Prodrug forms of kinase inhibitors and their use in therapy |
| MA33198B1 (fr) | 2009-03-20 | 2012-04-02 | Genentech Inc | Anticorps anti-her di-spécifiques |
| EP2451445B1 (en) | 2009-07-06 | 2019-04-03 | Boehringer Ingelheim International GmbH | Process for drying of bibw2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient |
| US9345661B2 (en) | 2009-07-31 | 2016-05-24 | Genentech, Inc. | Subcutaneous anti-HER2 antibody formulations and uses thereof |
| AU2010290199B2 (en) * | 2009-09-02 | 2016-10-27 | Auckland Uniservices Limited | Kinase inhibitors, prodrug forms thereof and their use in therapy |
| US9493578B2 (en) | 2009-09-02 | 2016-11-15 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
| JP2013510871A (ja) | 2009-11-12 | 2013-03-28 | ジェネンテック, インコーポレイテッド | 樹状突起棘の密度を促す方法 |
| CN102770456B (zh) | 2009-12-04 | 2018-04-06 | 弗·哈夫曼-拉罗切有限公司 | 多特异性抗体、抗体类似物、组合物和方法 |
| CN102712640A (zh) | 2010-01-12 | 2012-10-03 | 弗·哈夫曼-拉罗切有限公司 | 三环杂环化合物、其组合物和应用方法 |
| JP5981853B2 (ja) | 2010-02-18 | 2016-08-31 | ジェネンテック, インコーポレイテッド | ニューレグリンアンタゴニスト及び癌の治療におけるそれらの使用 |
| EP2542692B1 (en) | 2010-03-04 | 2016-08-24 | Carpén, Olli | Method for selecting patients for treatment with an egfr inhibitor |
| CN102869359A (zh) | 2010-03-17 | 2013-01-09 | 弗·哈夫曼-拉罗切有限公司 | 咪唑并吡啶和嘌呤化合物、组合物和使用方法 |
| JP2013523098A (ja) | 2010-03-29 | 2013-06-17 | ザイムワークス,インコーポレイテッド | 強化又は抑制されたエフェクター機能を有する抗体 |
| US8987272B2 (en) | 2010-04-01 | 2015-03-24 | Critical Outcome Technologies Inc. | Compounds and method for treatment of HIV |
| JP2013528787A (ja) | 2010-04-16 | 2013-07-11 | ジェネンテック, インコーポレイテッド | Pi3k/aktキナーゼ経路インヒビターの効果の予測バイオマーカーとしてのfox03a |
| WO2011146568A1 (en) | 2010-05-19 | 2011-11-24 | Genentech, Inc. | Predicting response to a her inhibitor |
| AU2011295919A1 (en) | 2010-08-31 | 2013-03-07 | Genentech, Inc. | Biomarkers and methods of treatment |
| BR112013006016A2 (pt) | 2010-09-15 | 2016-06-07 | Hoffmann La Roche | compostos de azabenzotiazol, composições e métodos de uso |
| WO2012060847A1 (en) | 2010-11-07 | 2012-05-10 | Targegen, Inc. | Compositions and methods for treating myelofibrosis |
| US9309322B2 (en) | 2010-11-12 | 2016-04-12 | Scott & White Healthcare (Swh) | Antibodies to tumor endothelial marker 8 |
| WO2012066061A1 (en) | 2010-11-19 | 2012-05-24 | F. Hoffmann-La Roche Ag | Pyrazolopyridines and pyrazolopyridines and their use as tyk2 inhibitors |
| CN102485735B (zh) * | 2010-12-02 | 2014-09-24 | 东莞南方医大代谢医学研发有限公司 | 6-果糖氨-4-芳胺基喹唑啉衍生物及其用途 |
| WO2012085176A1 (en) | 2010-12-23 | 2012-06-28 | F. Hoffmann-La Roche Ag | Tricyclic pyrazinone compounds, compositions and methods of use thereof as janus kinase inhibitors |
| KR20210043016A (ko) | 2011-03-04 | 2021-04-20 | 뉴젠 세러퓨틱스 인코포레이티드 | 알킨 치환된 퀴나졸린 화합물 및 그것의 사용 방법 |
| EP2683740B1 (en) | 2011-03-10 | 2018-07-04 | Omeros Corporation | Generation of anti-fn14 monoclonal antibodies by ex-vivo accelerated antibody evolution |
| CN102918029B (zh) * | 2011-05-17 | 2015-06-17 | 江苏康缘药业股份有限公司 | 4-苯胺-6-丁烯酰胺-7-烷醚喹唑啉衍生物及其制备方法和用途 |
| WO2013007768A1 (en) | 2011-07-13 | 2013-01-17 | F. Hoffmann-La Roche Ag | Tricyclic heterocyclic compounds, compositions and methods of use thereof as jak inhibitors |
| WO2013007765A1 (en) | 2011-07-13 | 2013-01-17 | F. Hoffmann-La Roche Ag | Fused tricyclic compounds for use as inhibitors of janus kinases |
| US9102724B2 (en) | 2011-08-12 | 2015-08-11 | Omeros Corporation | Anti-FZD10 monoclonal antibodies and methods for their use |
| HK1199255A1 (en) | 2011-08-12 | 2015-06-26 | F. Hoffmann-La Roche Ag | Indazole compounds, compositions and methods of use |
| US20140363438A1 (en) | 2011-08-17 | 2014-12-11 | Genentech, Inc. | Neuregulin antibodies and uses thereof |
| HK1198365A1 (en) | 2011-09-20 | 2015-04-10 | F. Hoffmann-La Roche Ag | Imidazopyridine compounds, compositions and methods of use |
| US9556141B2 (en) * | 2011-11-21 | 2017-01-31 | Basf Se | Process for preparing N-substituted 1H-pyrazole-5-carboxylate compounds and derivatives thereof |
| AU2012346540C1 (en) | 2011-11-30 | 2019-07-04 | Genentech, Inc. | ErbB3 mutations in cancer |
| CN104379602B (zh) | 2012-03-08 | 2017-05-03 | 哈洛齐梅公司 | 具有条件活性的抗表皮生长因子受体抗体及其使用方法 |
| MX2014011500A (es) | 2012-03-27 | 2014-12-05 | Genentech Inc | Diagnosticos y tratamientos relacionados a inhibidores her3. |
| HK1211235A1 (en) | 2013-02-22 | 2016-05-20 | 霍夫曼-拉罗奇有限公司 | Methods of treating cancer and preventing drug resistance |
| KR20150123250A (ko) | 2013-03-06 | 2015-11-03 | 제넨테크, 인크. | 암 약물 내성의 치료 및 예방 방법 |
| US10035801B2 (en) | 2013-03-13 | 2018-07-31 | Genentech, Inc. | Pyrazolo compounds and uses thereof |
| EP2968540A2 (en) | 2013-03-14 | 2016-01-20 | Genentech, Inc. | Combinations of a mek inhibitor compound with an her3/egfr inhibitor compound and methods of use |
| RU2015139054A (ru) | 2013-03-14 | 2017-04-19 | Дженентек, Инк. | Способы лечения рака и профилактики лекарственной резистентности рака |
| EP2968537A1 (en) | 2013-03-15 | 2016-01-20 | Genentech, Inc. | Methods of treating cancer and preventing cancer drug resistance |
| KR20160049003A (ko) | 2013-09-05 | 2016-05-04 | 제넨테크, 인크. | 항증식성 화합물 |
| HK1226081A1 (zh) | 2013-09-12 | 2017-09-22 | Halozyme, Inc. | 修饰的抗表皮生长因子受体抗体及其使用方法 |
| SG11201510740YA (en) | 2013-09-17 | 2016-01-28 | Obi Pharma Inc | Compositions of a carbohydrate vaccine for inducing immune responses and uses thereof in cancer treatment |
| AR097894A1 (es) | 2013-10-03 | 2016-04-20 | Hoffmann La Roche | Inhibidores terapéuticos de cdk8 o uso de los mismos |
| BR112016008477A2 (pt) | 2013-10-18 | 2017-10-03 | Genentech Inc | Corpos, ácido nucleico, célula hospedeira, método de produção de um anticorpo, imunoconjugado, formulação farmacêutica e usos do anticorpo |
| AU2014364606A1 (en) | 2013-12-17 | 2016-07-07 | Genentech, Inc. | Combination therapy comprising OX40 binding agonists and PD-1 axis binding antagonists |
| MY189089A (en) | 2013-12-17 | 2022-01-25 | Genentech Inc | Methods of treating cancers using pd-1 axis binding antagonists and taxanes |
| US9242965B2 (en) | 2013-12-31 | 2016-01-26 | Boehringer Ingelheim International Gmbh | Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors |
| EP3122900A1 (en) | 2014-03-24 | 2017-02-01 | F. Hoffmann-La Roche AG | Cancer treatment with c-met antagonists and correlation of the latter with hgf expression |
| AU2015241037B2 (en) | 2014-03-31 | 2020-10-15 | Genentech, Inc. | Anti-OX40 antibodies and methods of use |
| MX2016012779A (es) | 2014-03-31 | 2017-04-27 | Genentech Inc | Terapia de combinacion con agentes antiangiogénesis y agonistas de unión a ox40. |
| JP6814730B2 (ja) | 2014-09-05 | 2021-01-20 | ジェネンテック, インコーポレイテッド | 治療用化合物およびその使用 |
| JP2017529358A (ja) | 2014-09-19 | 2017-10-05 | ジェネンテック, インコーポレイテッド | がんの処置のためのcbp/ep300阻害剤およびbet阻害剤の使用 |
| CN107912040B (zh) | 2014-10-10 | 2021-04-06 | 基因泰克公司 | 作为组蛋白脱甲基酶抑制剂的吡咯烷酰胺化合物 |
| SG11201703448QA (en) | 2014-11-03 | 2017-05-30 | Genentech Inc | Assays for detecting t cell immune subsets and methods of use thereof |
| RU2017119231A (ru) | 2014-11-03 | 2018-12-06 | Дженентек, Инк. | Способы и биомаркеры для прогнозирования эффективности и оценки лечения агонистом ох40 |
| WO2016073282A1 (en) | 2014-11-06 | 2016-05-12 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and tigit inhibitors |
| WO2016077375A1 (en) | 2014-11-10 | 2016-05-19 | Genentech, Inc. | Bromodomain inhibitors and uses thereof |
| MA40940A (fr) | 2014-11-10 | 2017-09-19 | Constellation Pharmaceuticals Inc | Pyrrolopyridines substituées utilisées en tant qu'inhibiteurs de bromodomaines |
| MA40943A (fr) | 2014-11-10 | 2017-09-19 | Constellation Pharmaceuticals Inc | Pyrrolopyridines substituées utilisées en tant qu'inhibiteurs de bromodomaines |
| SG10201807625PA (en) | 2014-11-17 | 2018-10-30 | Genentech Inc | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
| WO2016086200A1 (en) | 2014-11-27 | 2016-06-02 | Genentech, Inc. | 4,5,6,7-tetrahydro-1 h-pyrazolo[4,3-c]pyridin-3-amine compounds as cbp and/or ep300 inhibitors |
| NZ732511A (en) | 2014-12-15 | 2018-11-30 | Univ Michigan Regents | Small molecule inhibitors of egfr and pi3k |
| EP3237639A2 (en) | 2014-12-23 | 2017-11-01 | Genentech, Inc. | Compositions and methods for treating and diagnosing chemotherapy-resistant cancers |
| WO2016109546A2 (en) | 2014-12-30 | 2016-07-07 | Genentech, Inc. | Methods and compositions for prognosis and treatment of cancers |
| EP3242875B1 (en) | 2015-01-09 | 2022-02-23 | Genentech, Inc. | 4,5-dihydroimidazole derivatives and their use as histone demethylase (kdm2b) inhibitors |
| WO2016112284A1 (en) | 2015-01-09 | 2016-07-14 | Genentech, Inc. | (piperidin-3-yl)(naphthalen-2-yl)methanone derivatives and related compounds as inhibitors of the histone demethylase kdm2b for the treatment of cancer |
| EP3242874B1 (en) | 2015-01-09 | 2018-10-31 | Genentech, Inc. | Pyridazinone derivatives and their use in the treatment of cancer |
| CN107531692B (zh) | 2015-01-29 | 2020-12-25 | 基因泰克公司 | 治疗化合物及其用途 |
| EP3250552B1 (en) | 2015-01-30 | 2019-03-27 | Genentech, Inc. | Therapeutic compounds and uses thereof |
| MA41598A (fr) | 2015-02-25 | 2018-01-02 | Constellation Pharmaceuticals Inc | Composés thérapeutiques de pyridazine et leurs utilisations |
| EP3280736A1 (en) | 2015-04-07 | 2018-02-14 | F. Hoffmann-La Roche AG | Antigen binding complex having agonistic activity and methods of use |
| MX2017014381A (es) | 2015-05-12 | 2018-03-02 | Genentech Inc | Metodos terapeuticos y diagnosticos para cancer. |
| JP7144935B2 (ja) | 2015-05-29 | 2022-09-30 | ジェネンテック, インコーポレイテッド | 癌のための治療方法及び診断方法 |
| EP3303399A1 (en) | 2015-06-08 | 2018-04-11 | H. Hoffnabb-La Roche Ag | Methods of treating cancer using anti-ox40 antibodies |
| KR20180025888A (ko) | 2015-06-08 | 2018-03-09 | 제넨테크, 인크. | 항-ox40 항체 및 pd-1 축 결합 길항제를 사용하여 암을 치료하는 방법 |
| CN116327953A (zh) | 2015-06-17 | 2023-06-27 | 豪夫迈·罗氏有限公司 | 使用pd-1轴结合拮抗剂和紫杉烷治疗局部晚期或转移性乳腺癌的方法 |
| AU2016313263B2 (en) | 2015-08-26 | 2021-02-04 | Fundación Del Sector Público Estatal Centro Nacional De Investigaciones Oncológicas Carlos III (F.S.P. CNIO) | Condensed tricyclic compounds as protein kinase inhibitors |
| EP3344806A4 (en) | 2015-09-04 | 2019-03-20 | OBI Pharma, Inc. | GLYCAN NETWORKS AND METHODS OF USE |
| MY186016A (en) | 2015-09-25 | 2021-06-14 | Genentech Inc | Anti-tigit antibodies and methods of use |
| EP3389662B1 (en) | 2015-12-16 | 2021-12-01 | Genentech, Inc. | Process for the preparation of tricyclic pi3k inhibitor compounds and methods for using the same for the treatment of cancer |
| KR20180094923A (ko) * | 2015-12-24 | 2018-08-24 | 교와 핫꼬 기린 가부시키가이샤 | α, β 불포화 아미드 화합물 |
| KR20180097615A (ko) | 2016-01-08 | 2018-08-31 | 에프. 호프만-라 로슈 아게 | Pd-1 축 결합 길항물질 및 항-cea/항-cd3 이중특이성 항체를 사용하는 cea-양성 암의 치료 방법 |
| WO2017122205A1 (en) | 2016-01-13 | 2017-07-20 | Hadasit Medical Research Services And Development Ltd. | Radiolabeled erlotinib analogs and uses thereof |
| KR102500659B1 (ko) | 2016-02-29 | 2023-02-16 | 제넨테크, 인크. | 암에 대한 치료 및 진단 방법 |
| US10980894B2 (en) | 2016-03-29 | 2021-04-20 | Obi Pharma, Inc. | Antibodies, pharmaceutical compositions and methods |
| US11041017B2 (en) | 2016-03-29 | 2021-06-22 | Obi Pharma, Inc. | Antibodies, pharmaceutical compositions and methods |
| WO2017180864A1 (en) | 2016-04-14 | 2017-10-19 | Genentech, Inc. | Anti-rspo3 antibodies and methods of use |
| JP2019515670A (ja) | 2016-04-15 | 2019-06-13 | ジェネンテック, インコーポレイテッド | がんをモニタリングし治療するための方法 |
| KR20190003958A (ko) | 2016-04-15 | 2019-01-10 | 제넨테크, 인크. | 암의 치료 및 모니터링 방법 |
| WO2017180581A1 (en) | 2016-04-15 | 2017-10-19 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| IL262296B2 (en) | 2016-04-22 | 2024-09-01 | Obi Pharma Inc | Cancer immunotherapy by immune activation or immune modulation via globo series antigens |
| WO2017194554A1 (en) | 2016-05-10 | 2017-11-16 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Combinations therapies for the treatment of cancer |
| MA45146A (fr) | 2016-05-24 | 2021-03-24 | Constellation Pharmaceuticals Inc | Dérivés de pyrazolopyridine pour le traitement du cancer |
| MA45122A (fr) | 2016-05-24 | 2019-04-10 | Constellation Pharmaceuticals Inc | Inhibiteurs hétérocycliques de cbp/ep300 et leur utilisation dans le traitement du cancer |
| PT3468997T (pt) | 2016-06-08 | 2023-12-07 | Debra Zack | Tratamento de doenças relacionadas com igg4 com anticorpos anti-cd19 com ligação cruzada a cd32b |
| CN109312407A (zh) | 2016-06-08 | 2019-02-05 | 豪夫迈·罗氏有限公司 | 用于癌症的诊断和治疗方法 |
| CN110072545A (zh) | 2016-07-27 | 2019-07-30 | 台湾浩鼎生技股份有限公司 | 免疫原性/治疗性聚糖组合物及其用途 |
| JP7121724B2 (ja) | 2016-07-29 | 2022-08-18 | オービーアイ ファーマ,インコーポレイテッド | ヒト抗体、医薬組成物及び方法 |
| EP3494139B1 (en) | 2016-08-05 | 2022-01-12 | F. Hoffmann-La Roche AG | Multivalent and multiepitopic anitibodies having agonistic activity and methods of use |
| JP7250674B2 (ja) | 2016-08-08 | 2023-04-03 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | がんの治療及び診断方法 |
| JP7579056B2 (ja) | 2016-10-06 | 2024-11-07 | ジェネンテック, インコーポレイテッド | がんのための治療方法及び診断方法 |
| WO2018081648A2 (en) | 2016-10-29 | 2018-05-03 | Genentech, Inc. | Anti-mic antibidies and methods of use |
| AU2017361549B2 (en) | 2016-11-21 | 2023-12-21 | Obi Pharma, Inc. | Conjugated biological molecules, pharmaceutical compositions and methods |
| EP3589754B1 (en) | 2017-03-01 | 2023-06-28 | F. Hoffmann-La Roche AG | Diagnostic and therapeutic methods for cancer |
| JP2020516638A (ja) | 2017-04-13 | 2020-06-11 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | がんを処置する方法における使用のための、インターロイキン2イムノコンジュゲート、cd40アゴニスト、および任意選択のpd−1軸結合アンタゴニスト |
| AU2018304458B2 (en) | 2017-07-21 | 2021-12-09 | Foundation Medicine, Inc. | Therapeutic and diagnostic methods for cancer |
| AU2018316343B2 (en) | 2017-08-11 | 2025-06-12 | Genentech, Inc. | Anti-CD8 antibodies and uses thereof |
| EP3679159A1 (en) | 2017-09-08 | 2020-07-15 | H. Hoffnabb-La Roche Ag | Diagnostic and therapeutic methods for cancer |
| WO2019084395A1 (en) | 2017-10-27 | 2019-05-02 | University Of Virginia Patent Foundation | COMPOUNDS AND METHODS FOR REGULATING, LIMITING OR INHIBITING AVIL EXPRESSION |
| JP7544597B2 (ja) | 2017-11-06 | 2024-09-03 | ジェネンテック, インコーポレイテッド | がんの診断及び療法 |
| EP3740756A4 (en) | 2018-01-15 | 2021-10-27 | Epiaxis Therapeutics Pty Ltd | AGENTS AND METHODS FOR PREDICTING THE THERAPEUTIC RESPONSE |
| CN117624045A (zh) | 2018-01-26 | 2024-03-01 | 埃克塞里艾克西斯公司 | 用于治疗激酶依赖性病症的化合物 |
| CR20250117A (es) | 2018-01-26 | 2025-05-09 | Exelixis Inc | COMPUESTOS PARA EL TRATAMIENTO DE TRASTORNOS DEPENDIENTES DE CINASAS (Divisional 2020-0355) |
| WO2019148043A1 (en) | 2018-01-26 | 2019-08-01 | Exelixis, Inc. | Compounds for the treatment of kinase-dependent disorders |
| AU2019225249A1 (en) | 2018-02-26 | 2020-09-17 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-PD-L1 antagonist antibodies |
| US20210363590A1 (en) | 2018-05-21 | 2021-11-25 | Nanostring Technologies, Inc. | Molecular gene signatures and methods of using same |
| SG11202012446UA (en) | 2018-06-23 | 2021-01-28 | Genentech Inc | Methods of treating lung cancer with a pd-1 axis binding antagonist, a platinum agent, and a topoisomerase ii inhibitor |
| TWI853822B (zh) | 2018-06-27 | 2024-09-01 | 台灣浩鼎生技股份有限公司 | 用於糖蛋白工程的糖苷合成酶變體及其使用方法 |
| EP3823611A1 (en) | 2018-07-18 | 2021-05-26 | Genentech, Inc. | Methods of treating lung cancer with a pd-1 axis binding antagonist, an antimetabolite, and a platinum agent |
| CN112805267B (zh) | 2018-09-03 | 2024-03-08 | 豪夫迈·罗氏有限公司 | 用作tead调节剂的甲酰胺和磺酰胺衍生物 |
| KR20210063330A (ko) | 2018-09-19 | 2021-06-01 | 제넨테크, 인크. | 방광암에 대한 치료 및 진단 방법 |
| AU2019342133B8 (en) | 2018-09-21 | 2025-08-07 | Genentech, Inc. | Diagnostic methods for triple-negative breast cancer |
| KR20210137422A (ko) | 2018-09-25 | 2021-11-17 | 블랙 다이아몬드 테라퓨틱스, 인코포레이티드 | 티로신 키나아제 억제제로서의 퀴나졸린 유도체, 조성물, 이들의 제조 방법 및 이들의 용도 |
| EP3867405A4 (en) | 2018-10-17 | 2022-07-20 | The University of Queensland | Epigenetic biomarker and uses therefor |
| KR20210079311A (ko) | 2018-10-18 | 2021-06-29 | 제넨테크, 인크. | 육종성 신장암에 대한 진단과 치료 방법 |
| WO2020163589A1 (en) | 2019-02-08 | 2020-08-13 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| US20220146495A1 (en) | 2019-02-27 | 2022-05-12 | Epiaxis Therapeutics Pty Ltd | Methods and agents for assessing t-cell function and predicting response to therapy |
| CN113710706A (zh) | 2019-02-27 | 2021-11-26 | 豪夫迈·罗氏有限公司 | 用于抗tigit抗体和抗cd20抗体或抗cd38抗体治疗的给药 |
| WO2020223233A1 (en) | 2019-04-30 | 2020-11-05 | Genentech, Inc. | Prognostic and therapeutic methods for colorectal cancer |
| WO2020226986A2 (en) | 2019-05-03 | 2020-11-12 | Genentech, Inc. | Methods of treating cancer with an anti-pd-l1 antibody |
| CN112300279A (zh) | 2019-07-26 | 2021-02-02 | 上海复宏汉霖生物技术股份有限公司 | 针对抗cd73抗体和变体的方法和组合物 |
| CN119390683A (zh) | 2019-08-15 | 2025-02-07 | 黑钻治疗公司 | 炔基喹唑啉化合物 |
| KR20220057563A (ko) | 2019-09-04 | 2022-05-09 | 제넨테크, 인크. | Cd8 결합제 및 이의 용도 |
| JP2022551422A (ja) | 2019-09-26 | 2022-12-09 | エグゼリクシス, インコーポレイテッド | ピリドン化合物およびタンパク質キナーゼの調節における使用の方法 |
| MX2022003610A (es) | 2019-09-27 | 2022-04-20 | Genentech Inc | Administracion de dosis para tratamiento con anticuerpos antagonistas anti-tigit y anti-pd-l1. |
| WO2021083949A1 (en) | 2019-10-29 | 2021-05-06 | F. Hoffmann-La Roche Ag | Bifunctional compounds for the treatment of cancer |
| KR20220092580A (ko) | 2019-11-06 | 2022-07-01 | 제넨테크, 인크. | 혈액암의 치료를 위한 진단과 치료 방법 |
| CN114728905B (zh) | 2019-11-13 | 2025-08-01 | 基因泰克公司 | 治疗性化合物及使用方法 |
| AR120741A1 (es) | 2019-12-13 | 2022-03-16 | Genentech Inc | Anticuerpos anti-ly6g6d y métodos de uso |
| EP4076667A1 (en) | 2019-12-20 | 2022-10-26 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
| WO2021194481A1 (en) | 2020-03-24 | 2021-09-30 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
| WO2022050954A1 (en) | 2020-09-04 | 2022-03-10 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
| AU2021212662A1 (en) | 2020-01-27 | 2022-08-11 | F. Hoffmann-La Roche Ag | Methods for treatment of cancer with an anti-TIGIT antagonist antibody |
| WO2021177980A1 (en) | 2020-03-06 | 2021-09-10 | Genentech, Inc. | Combination therapy for cancer comprising pd-1 axis binding antagonist and il6 antagonist |
| EP4127724A1 (en) | 2020-04-03 | 2023-02-08 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
| EP4143345A1 (en) | 2020-04-28 | 2023-03-08 | Genentech, Inc. | Methods and compositions for non-small cell lung cancer immunotherapy |
| WO2021257503A1 (en) | 2020-06-16 | 2021-12-23 | Genentech, Inc. | Methods and compositions for treating triple-negative breast cancer |
| BR112022025801A2 (pt) | 2020-06-18 | 2023-10-03 | Hoffmann La Roche | Métodos para tratar um paciente e para tratar um paciente com escc avançado, kit, anticorpo, uso de um anticorpo e uso de um antagonista de ligação |
| CN115997123A (zh) | 2020-06-30 | 2023-04-21 | 国家医疗保健研究所 | 用于预测实体癌患者在术前辅助治疗后复发和/或死亡风险的方法 |
| JP7741831B2 (ja) | 2020-06-30 | 2025-09-18 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 術前補助療法及び根治手術後の固形がんを患っている患者の再発及び/又は死亡のリスクを予測するための方法 |
| US11787775B2 (en) | 2020-07-24 | 2023-10-17 | Genentech, Inc. | Therapeutic compounds and methods of use |
| WO2022031749A1 (en) | 2020-08-03 | 2022-02-10 | Genentech, Inc. | Diagnostic and therapeutic methods for lymphoma |
| WO2022036146A1 (en) | 2020-08-12 | 2022-02-17 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| KR20230078657A (ko) | 2020-08-27 | 2023-06-02 | 에노시 테라퓨틱스 코퍼레이션 | 자가면역 질환 및 암을 치료하기 위한 방법 및 조성물 |
| IL301524A (en) | 2020-09-23 | 2023-05-01 | Erasca Inc | Tricyclic pyridones and pyrimidones |
| WO2022076462A1 (en) | 2020-10-05 | 2022-04-14 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| US20230107642A1 (en) | 2020-12-18 | 2023-04-06 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
| KR20230155422A (ko) | 2020-12-22 | 2023-11-10 | 메카니스틱 테라퓨틱스 엘엘씨 | Egfr 및/또는 pi3k 억제제로서의 치환된 아미노벤질헤테로아릴 화합물 |
| US20240368150A1 (en) | 2021-02-12 | 2024-11-07 | Hoffmann-La Roche Inc. | Bicyclic tetrahydroazepine derivatives for the treatment of cancer |
| JP2024507794A (ja) | 2021-02-19 | 2024-02-21 | エグゼリクシス, インコーポレイテッド | ピリドン化合物および使用方法 |
| US20240246940A1 (en) * | 2021-04-22 | 2024-07-25 | Voronoi Inc. | Heteroaryl derivative compound and use thereof |
| EP4347603A1 (en) | 2021-05-25 | 2024-04-10 | Erasca, Inc. | Sulfur-containing heteroaromatic tricyclic kras inhibitors |
| WO2022266206A1 (en) | 2021-06-16 | 2022-12-22 | Erasca, Inc. | Kras inhibitor conjugates |
| CA3226019A1 (en) | 2021-07-20 | 2023-01-26 | Ags Therapeutics Sas | Extracellular vesicles from microalgae, their preparation, and uses |
| EP4384522A1 (en) | 2021-08-10 | 2024-06-19 | Erasca, Inc. | Selective kras inhibitors |
| JP2024541508A (ja) | 2021-11-24 | 2024-11-08 | ジェネンテック, インコーポレイテッド | 治療用インダゾール化合物およびがんの治療における使用方法 |
| WO2023097194A2 (en) | 2021-11-24 | 2023-06-01 | Genentech, Inc. | Therapeutic compounds and methods of use |
| WO2023128350A1 (ko) * | 2021-12-30 | 2023-07-06 | 주식회사 비투에스바이오 | 헤테로아릴 유도체 및 이를 유효성분으로 포함하는 암의 예방 또는 치료용 약학적 조성물 |
| WO2023144127A1 (en) | 2022-01-31 | 2023-08-03 | Ags Therapeutics Sas | Extracellular vesicles from microalgae, their biodistribution upon administration, and uses |
| AU2022450448A1 (en) | 2022-04-01 | 2024-10-10 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| WO2023219613A1 (en) | 2022-05-11 | 2023-11-16 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| AU2023284422A1 (en) | 2022-06-07 | 2024-12-19 | Genentech, Inc. | Method for determining the efficacy of a lung cancer treatment comprising an anti-pd-l1 antagonist and an anti-tigit antagonist antibody |
| AU2023305619A1 (en) | 2022-07-13 | 2025-01-23 | F. Hoffmann-La Roche Ag | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| EP4558524A1 (en) | 2022-07-19 | 2025-05-28 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| CN119677732A (zh) | 2022-08-11 | 2025-03-21 | 豪夫迈·罗氏有限公司 | 双环四氢氮杂䓬衍生物 |
| CR20250042A (es) | 2022-08-11 | 2025-03-25 | Hoffmann La Roche | Derivados de tetrahidrotiazepina bicíclicos |
| CA3262845A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | BICYCLIC TETRAHYDROTHIAZEPINE DERIVATIVES |
| EP4568746A1 (en) | 2022-08-11 | 2025-06-18 | F. Hoffmann-La Roche AG | Bicyclic tetrahydrothiazepine derivatives |
| WO2024085242A2 (en) | 2022-10-21 | 2024-04-25 | Kawasaki Institute Of Industrial Promotion | Non-fouling or super stealth vesicle |
| EP4608424A1 (en) | 2022-10-24 | 2025-09-03 | AGS Therapeutics SAS | Extracellular vesicles from microalgae, their biodistribution upon intranasal administration, and uses thereof |
| EP4609201A1 (en) | 2022-10-25 | 2025-09-03 | Genentech, Inc. | Therapeutic and diagnostic methods for multiple myeloma |
| EP4665735A1 (en) | 2023-02-17 | 2025-12-24 | Erasca, Inc. | Kras inhibitors |
| WO2024233341A1 (en) | 2023-05-05 | 2024-11-14 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| WO2024254455A1 (en) | 2023-06-08 | 2024-12-12 | Genentech, Inc. | Macrophage signatures for diagnostic and therapeutic methods for lymphoma |
| WO2025024257A1 (en) | 2023-07-21 | 2025-01-30 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| TW202515614A (zh) | 2023-08-25 | 2025-04-16 | 美商建南德克公司 | 治療非小細胞肺癌之方法及組成物 |
| WO2025176843A1 (en) | 2024-02-21 | 2025-08-28 | Ags Therapeutics Sas | Microalgae extracellular vesicle based gene therapy vectors (mev-gtvs), their preparation, and uses thereof |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ243082A (en) * | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
| AU661533B2 (en) * | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| JP2994165B2 (ja) * | 1992-06-26 | 1999-12-27 | ゼネカ・リミテッド | キナゾリン誘導体、その製造法および該キナゾリン誘導体を含有する抗癌作用を得るための医薬調剤 |
| GB9323290D0 (en) * | 1992-12-10 | 1994-01-05 | Zeneca Ltd | Quinazoline derivatives |
| GB9314893D0 (en) * | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
| GB9510757D0 (en) * | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
| TW321649B (enExample) * | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
| GB9508565D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quiazoline derivative |
| US5760041A (en) * | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
| ES2174250T5 (es) * | 1996-04-12 | 2010-04-21 | Warner-Lambert Company Llc | Inhibidores irreversibles de tirosina quinasas. |
| TW436485B (en) * | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
-
1998
- 1998-07-28 TW TW087112356A patent/TW436485B/zh not_active IP Right Cessation
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- 2000-01-31 NO NO20000487A patent/NO317093B1/no not_active IP Right Cessation
-
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- 2002-06-06 NZ NZ519387A patent/NZ519387A/en not_active IP Right Cessation
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| CN107400094B (zh) * | 2017-09-08 | 2020-04-03 | 贾玉庆 | 喹唑啉基羧酸酯类化合物及其用途 |
| CN109608334A (zh) * | 2019-01-11 | 2019-04-12 | 盐城通海生物科技有限公司 | 一种合成4-甲氧基巴豆酸甲酯的方法 |
| CN109608334B (zh) * | 2019-01-11 | 2021-07-13 | 盐城通海生物科技有限公司 | 一种合成4-甲氧基巴豆酸甲酯的方法 |
| CN113307797A (zh) * | 2020-07-10 | 2021-08-27 | 江南大学 | 一种多取代喹唑啉类化合物及其应用 |
| CN115894455A (zh) * | 2021-09-30 | 2023-04-04 | 北京赛特明强医药科技有限公司 | 一种喹唑啉类化合物、组合物及其应用 |
| CN115894455B (zh) * | 2021-09-30 | 2024-04-19 | 北京赛特明强医药科技有限公司 | 一种喹唑啉类化合物、组合物及其应用 |
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