CA2389767C - Quinazoline derivatives as vegf inhibitors - Google Patents
Quinazoline derivatives as vegf inhibitors Download PDFInfo
- Publication number
- CA2389767C CA2389767C CA2389767A CA2389767A CA2389767C CA 2389767 C CA2389767 C CA 2389767C CA 2389767 A CA2389767 A CA 2389767A CA 2389767 A CA2389767 A CA 2389767A CA 2389767 C CA2389767 C CA 2389767C
- Authority
- CA
- Canada
- Prior art keywords
- quinazoline
- ylmethoxy
- methoxy
- pharmaceutically acceptable
- acceptable salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
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- 239000002525 vasculotropin inhibitor Substances 0.000 title description 2
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- 125000001424 substituent group Chemical group 0.000 claims abstract description 17
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 3
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- 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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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—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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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
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- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99402759 | 1999-11-05 | ||
| EP99402759.7 | 1999-11-05 | ||
| EP99402877.7 | 1999-11-19 | ||
| EP99402877 | 1999-11-19 | ||
| PCT/GB2000/004181 WO2001032651A1 (en) | 1999-11-05 | 2000-11-01 | Quinazoline derivatives as vegf inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2389767A1 CA2389767A1 (en) | 2001-05-10 |
| CA2389767C true CA2389767C (en) | 2010-03-23 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2389767A Expired - Lifetime CA2389767C (en) | 1999-11-05 | 2000-11-01 | Quinazoline derivatives as vegf inhibitors |
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| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| SI1676845T1 (sl) | 1999-11-05 | 2008-10-31 | Astrazeneca Ab | Novi kinazolinski derivati |
| GB0008269D0 (en) * | 2000-04-05 | 2000-05-24 | Astrazeneca Ab | Combination chemotherapy |
| DE60121931T2 (de) | 2000-04-07 | 2007-03-01 | Astrazeneca Ab | Chinazolinverbindungen |
| GB0126879D0 (en) * | 2001-11-08 | 2002-01-02 | Astrazeneca Ab | Combination therapy |
| WO2003063904A2 (en) * | 2002-01-29 | 2003-08-07 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw | Tissue adhesion formation control |
| US7268230B2 (en) | 2002-02-01 | 2007-09-11 | Astrazeneca Ab | Quinazoline compounds |
| 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 |
| US7576074B2 (en) * | 2002-07-15 | 2009-08-18 | Rice Kenneth D | Receptor-type kinase modulators and methods of use |
| BR0313116A (pt) * | 2002-08-09 | 2005-07-05 | Astrazeneca Ab | Método para a produção de um efeito redutor de permeabilidade vascular e/ou antiangiogênico em um animal de sangue quente tal como um humano, método para o tratamento de um câncer em um animal de sangue quente tal como humano, e, uso de zd6474 ou de um seu sal farmaceuticamente aceitável. |
| DE10237423A1 (de) | 2002-08-16 | 2004-02-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verwendung von LCK-Inhibitoren für die Behandlung von immunologischen Erkrankungen |
| GB0223380D0 (en) * | 2002-10-09 | 2002-11-13 | Astrazeneca Ab | Combination therapy |
| NZ539408A (en) | 2002-11-04 | 2007-09-28 | Astrazeneca Ab | Quinazoline derivatives as SRC tyrosine kinase inhibitors for treating solid tumours |
| DE602004032310D1 (de) * | 2003-02-13 | 2011-06-01 | Astrazeneca Ab | Kombinationstherapie von zd6474 mit 5-fu oder/und cpt-11 |
| US20050043233A1 (en) * | 2003-04-29 | 2005-02-24 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis |
| GB0316176D0 (en) * | 2003-07-10 | 2003-08-13 | Astrazeneca Ab | Combination therapy |
| JP2007526886A (ja) * | 2003-07-10 | 2007-09-20 | アストラゼネカ アクチボラグ | 血管新生および／または血管透過性増大に関連する疾患の処置における、プラチナ系抗腫瘍剤および任意の電離放射線と組み合わせてのキナゾリン誘導体ｚｄ６４７４の使用 |
| MXPA06000508A (es) | 2003-07-18 | 2006-04-05 | Amgen Inc | Agentes de union especifica al factor del crecimiento de los hepatocitos. |
| GB0317665D0 (en) | 2003-07-29 | 2003-09-03 | Astrazeneca Ab | Qinazoline derivatives |
| GB0318423D0 (en) * | 2003-08-06 | 2003-09-10 | Astrazeneca Ab | Chemical compounds |
| PL1667991T3 (pl) * | 2003-09-16 | 2008-12-31 | Astrazeneca Ab | Pochodne chinazoliny jako inhibitory kinazy tyrozynowej |
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| GB0330002D0 (en) * | 2003-12-24 | 2004-01-28 | Astrazeneca Ab | Quinazoline derivatives |
| ATE413389T1 (de) | 2004-02-03 | 2008-11-15 | Astrazeneca Ab | Chinazolinderivate |
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| GB0411378D0 (en) * | 2004-05-21 | 2004-06-23 | Astrazeneca Ab | Pharmaceutical compositions |
| EP2277595A3 (en) | 2004-06-24 | 2011-09-28 | Novartis Vaccines and Diagnostics, Inc. | Compounds for immunopotentiation |
| JP2008514577A (ja) * | 2004-09-27 | 2008-05-08 | アストラゼネカ アクチボラグ | Ｚｄ６４７４及びイマチニブを含んでなる組合せ |
| GB0424339D0 (en) * | 2004-11-03 | 2004-12-08 | Astrazeneca Ab | Combination therapy |
| WO2006060318A2 (en) | 2004-11-30 | 2006-06-08 | Amgen Inc. | Quinolines and quinazoline analogs and their use as medicaments for treating cancer |
| PL1838733T3 (pl) | 2004-12-21 | 2012-02-29 | Medimmune Ltd | Przeciwciała skierowane przeciwko angiopoetynie-2 i ich zastosowania |
| CN1854130B (zh) * | 2005-04-15 | 2011-04-20 | 中国医学科学院药物研究所 | 喹唑啉衍生物、及其制法和药物组合物与用途 |
| HRP20120154T1 (hr) | 2005-05-18 | 2012-03-31 | Array Biopharma | HETEROCIKLIČKI INHIBITORI MEK-a I METODE NJIHOVE UPORABE |
| AU2011203358B2 (en) * | 2005-09-30 | 2013-05-30 | Genzyme Corporation | Chemical process |
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| GB0519879D0 (en) * | 2005-09-30 | 2005-11-09 | Astrazeneca Ab | Chemical process |
| US20080108664A1 (en) | 2005-12-23 | 2008-05-08 | Liu Belle B | Solid-state form of AMG 706 and pharmaceutical compositions thereof |
| JO2660B1 (en) | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
| AR059066A1 (es) | 2006-01-27 | 2008-03-12 | Amgen Inc | Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf) |
| ATE489380T1 (de) | 2006-02-10 | 2010-12-15 | Amgen Inc | Hydratformen von amg706 |
| AR060358A1 (es) | 2006-04-06 | 2008-06-11 | Novartis Vaccines & Diagnostic | Quinazolinas para la inhibicion de pdk 1 |
| TW200813091A (en) | 2006-04-10 | 2008-03-16 | Amgen Fremont Inc | Targeted binding agents directed to uPAR and uses thereof |
| WO2007124288A1 (en) | 2006-04-19 | 2007-11-01 | Novartis Ag | Indazole compounds and methods for inhibition of cdc7 |
| PE20121506A1 (es) | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
| US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| CL2007002225A1 (es) | 2006-08-03 | 2008-04-18 | Astrazeneca Ab | Agente de union especifico para un receptor del factor de crecimiento derivado de plaquetas (pdgfr-alfa); molecula de acido nucleico que lo codifica; vector y celula huesped que la comprenden; conjugado que comprende al agente; y uso del agente de un |
| KR20090047509A (ko) | 2006-08-04 | 2009-05-12 | 다케다 야쿠힌 고교 가부시키가이샤 | 융합 헤테로시클릭 유도체 및 이의 용도 |
| AU2007287430B2 (en) | 2006-08-23 | 2011-07-21 | Kudos Pharmaceuticals Limited | 2-methylmorpholine pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mTOR inhibitors |
| JP2010504949A (ja) * | 2006-09-29 | 2010-02-18 | アストラゼネカ アクチボラグ | Ｚｄ６４７４とベバシズマブの癌療法のための組合せ |
| WO2008044045A1 (en) | 2006-10-12 | 2008-04-17 | Astex Therapeutics Limited | Pharmaceutical combinations |
| EP2073803B1 (en) | 2006-10-12 | 2018-09-19 | Astex Therapeutics Limited | Pharmaceutical combinations |
| WO2008046242A1 (fr) * | 2006-10-16 | 2008-04-24 | Institute Of Mataria Medica, Chinese Academy Of Medical Sciences | Nouveaux dérivés quinazolines, leurs procédés de préparation et leurs utilisations |
| 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 |
| EP2125781A2 (en) | 2006-12-20 | 2009-12-02 | Amgen Inc. | Substituted heterocycles and methods of use |
| AU2008205252B2 (en) | 2007-01-09 | 2013-02-21 | Amgen Inc. | Bis-aryl amide derivatives useful for the treatment of cancer |
| KR20090116782A (ko) | 2007-02-06 | 2009-11-11 | 베링거 인겔하임 인터내셔날 게엠베하 | 바이사이클릭 헤테로사이클, 당해 화합물을 함유하는 약물, 이의 용도 및 이의 제조방법 |
| US20080190689A1 (en) * | 2007-02-12 | 2008-08-14 | Ballard Ebbin C | Inserts for engine exhaust systems |
| MX2009008531A (es) | 2007-02-16 | 2009-08-26 | Amgen Inc | Cetonas de heterociclilo que contienen nitrogeno y su uso como inhibidores de c-met. |
| AR065784A1 (es) | 2007-03-20 | 2009-07-01 | Dainippon Sumitomo Pharma Co | Derivados de 8-oxo adenina,medicamentos que los contienen y usos como agentes terapeuticos para enfermedades alergicas, antivirales o antibacterianas. |
| EP2138497A4 (en) | 2007-03-20 | 2012-01-04 | Dainippon Sumitomo Pharma Co | NEW ADENINE CONNECTION |
| US8914063B2 (en) | 2007-05-15 | 2014-12-16 | Lg Electronics Inc. | Mobile terminal equipped with mode setting key and method of controlling the mobile terminal |
| PE20090370A1 (es) | 2007-06-05 | 2009-04-30 | Takeda Pharmaceutical | Derivados de heterociclo fusionado como inhibidores de quinasa |
| CL2008002444A1 (es) | 2007-08-21 | 2009-09-04 | Amgen Inc | Anticuerpo o fragmento del mismo que se une a la proteina c-fms humana; molecula de acido nucleico que la codifica; vector y celula huesped; metodo de elaboracion; composicion farmaceutica que la comprende; y su uso para tratar o prevenir una condicion asociada con c-fms en un paciente. |
| WO2009025358A1 (ja) | 2007-08-23 | 2009-02-26 | Takeda Pharmaceutical Company Limited | 複素環化合物およびその用途 |
| WO2009047563A1 (en) | 2007-10-11 | 2009-04-16 | Astrazeneca Ab | Pyrrolo [2, 3 -d] pyrimidin derivatives as protein kinase b inhibitors |
| JP5421925B2 (ja) | 2007-12-19 | 2014-02-19 | ジェネンテック， インコーポレイテッド | ５−アニリノイミダゾピリジン及び使用の方法 |
| UY31545A1 (es) | 2007-12-20 | 2009-08-03 | Nuevos derivados de 2-carboxamida cianoaminourea, sus sales y profarmacos farmacéuticamente aceptables, procesos de preparacion y aplicaciones | |
| BRPI0819505A2 (pt) | 2007-12-21 | 2017-04-04 | Genentech Inc | "composto, composição farmacêutica, método para inibir o crescimento celular anormal e método para tratar uma doença inflamatória" |
| US8609673B2 (en) * | 2008-01-22 | 2013-12-17 | Concert Pharmaceuticals, Inc. | Vandetanib derivatives |
| BRPI0907916A2 (pt) | 2008-02-07 | 2015-07-28 | Boehringer Ingelheim Int | Heterociclos espirociclos, medicamentos contendo esses compostos, e processos para preparar os mesmos |
| KR20100135754A (ko) * | 2008-02-21 | 2010-12-27 | 아스트라제네카 아베 | 병용 요법 238 |
| NZ589883A (en) | 2008-05-13 | 2012-06-29 | Astrazeneca Ab | Fumarate salt of 4- (3-chloro-2-fluoroanilino) -7-methoxy-6- { [1- (n-methylcarbamoylmethyl) piperidin- 4-yl] oxy} quinazoline |
| WO2010005527A1 (en) | 2008-06-30 | 2010-01-14 | Angioblast Systems, Inc. | Treatment of eye diseases and excessive neovascularization using a combined therapy |
| 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 |
| WO2010032060A1 (en) | 2008-09-19 | 2010-03-25 | Medimmune Llc | Antibodies directed to dll4 and uses thereof |
| 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 |
| TW201028410A (en) | 2008-12-22 | 2010-08-01 | Astrazeneca Ab | Chemical compounds 610 |
| US20120114667A1 (en) | 2008-12-23 | 2012-05-10 | Medimmune Limited | TARGETED BINDING AGENTS DIRECTED TO a5BETA1 AND USES THEREOF |
| CN105175434A (zh) | 2009-02-05 | 2015-12-23 | 伊缪诺金公司 | 新型苯并二氮杂*衍生物 |
| ES2529205T3 (es) | 2009-03-13 | 2015-02-17 | Cellzome Limited | Derivados de pirimidina como inhibidores de mTOR |
| WO2010108503A1 (en) | 2009-03-24 | 2010-09-30 | Life & Brain Gmbh | Promotion of neuronal integration in neural stem cell grafts |
| WO2010118986A1 (en) | 2009-04-14 | 2010-10-21 | Cellzome Limited | Fluoro substituted pyrimidine compounds as jak3 inhibitors |
| US8293753B2 (en) | 2009-07-02 | 2012-10-23 | Novartis Ag | Substituted 2-carboxamide cycloamino ureas |
| US20120172385A1 (en) | 2009-09-11 | 2012-07-05 | Richard John Harrison | Ortho substituted pyrimidine compounds as jak inhibitors |
| CN102666545B (zh) | 2009-10-20 | 2016-04-06 | 塞尔卓姆有限公司 | 作为jak抑制剂的杂环吡唑并嘧啶类似物 |
| CN102070608A (zh) * | 2009-11-19 | 2011-05-25 | 天津药物研究院 | 4-取代苯胺基-7-取代烷氧基-喹唑啉衍生物、其制备方法和用途 |
| KR101740171B1 (ko) | 2009-11-24 | 2017-05-25 | 메디뮨 리미티드 | Ｂ７―ｈ１에 대한 표적화된 결합 물질 |
| WO2011068233A1 (en) | 2009-12-03 | 2011-06-09 | Dainippon Sumitomo Pharma Co., Ltd. | Imidazoquinolines which act via toll - like receptors (tlr) |
| KR20130009760A (ko) | 2010-02-10 | 2013-01-23 | 이뮤노젠 아이엔씨 | Ｃｄ２０ 항체 및 이의 용도 |
| WO2011107585A1 (en) | 2010-03-04 | 2011-09-09 | Cellzome Limited | Morpholino substituted urea derivatives as mtor inhibitors |
| MX2012012328A (es) | 2010-04-30 | 2013-05-06 | Cellzome Ltd | Compuestos pirazol como inhibidores de jak. |
| SA111320519B1 (ar) | 2010-06-11 | 2014-07-02 | Astrazeneca Ab | مركبات بيريميدينيل للاستخدام كمثبطات atr |
| WO2011161217A2 (en) | 2010-06-23 | 2011-12-29 | Palacký University in Olomouc | Targeting of vegfr2 |
| WO2012000970A1 (en) | 2010-07-01 | 2012-01-05 | Cellzome Limited | Triazolopyridines as tyk2 inhibitors |
| AR082418A1 (es) | 2010-08-02 | 2012-12-05 | Novartis Ag | Formas cristalinas de 1-(4-metil-5-[2-(2,2,2-trifluoro-1,1-dimetil-etil)-piridin-4-il]-tiazol-2-il)-amida de 2-amida del acido (s)-pirrolidin-1,2-dicarboxilico |
| US9040545B2 (en) | 2010-08-20 | 2015-05-26 | Cellzome Limited | Heterocyclyl pyrazolopyrimidine analogues as selective JAK inhibitors |
| BR112013004673A8 (pt) | 2010-08-31 | 2018-01-02 | Genentech Inc | biomarcadores e métodos de tratamento. |
| CN103298794A (zh) | 2010-11-09 | 2013-09-11 | 塞尔卓姆有限公司 | 作为tyk2抑制剂的吡啶化合物及其氮杂类似物 |
| CN102532103B (zh) * | 2010-12-20 | 2014-07-09 | 天津药物研究院 | 喹唑啉芳基脲衍生物及其制备方法和用途 |
| EP2670753B1 (en) | 2011-01-31 | 2016-10-19 | Novartis AG | Novel heterocyclic derivatives |
| BR112013020540B1 (pt) | 2011-02-15 | 2020-12-29 | Immunogen, Inc | métodos para preparação de conjugados compreendendo agente de ligação à célula conjugado a composto citotóxico com grupo ligante |
| WO2012110773A1 (en) | 2011-02-17 | 2012-08-23 | Cancer Therapeutics Crc Pty Limited | Fak inhibitors |
| CA2827172C (en) | 2011-02-17 | 2019-02-26 | Cancer Therapeutics Crc Pty Limited | Selective fak inhibitors |
| SG193580A1 (en) | 2011-03-23 | 2013-10-30 | Amgen Inc | Fused tricyclic dual inhibitors of cdk 4/6 and flt3 |
| WO2012136622A1 (en) | 2011-04-04 | 2012-10-11 | Cellzome Limited | Dihydropyrrolo pyrimidine derivatives as mtor inhibitors |
| WO2012143320A1 (en) | 2011-04-18 | 2012-10-26 | Cellzome Limited | (7h-pyrrolo[2,3-d]pyrimidin-2-yl)amine compounds as jak3 inhibitors |
| WO2013014162A1 (en) | 2011-07-28 | 2013-01-31 | Cellzome Limited | Heterocyclyl pyrimidine analogues as jak inhibitors |
| WO2013017480A1 (en) | 2011-07-29 | 2013-02-07 | Cellzome Limited | Pyrazolo[4,3-c]pyridine derivatives as jak inhibitors |
| WO2013017479A1 (en) | 2011-07-29 | 2013-02-07 | Cellzome Limited | Pyrazolo[4,3-c]pyridine derivatives as jak inhibitors |
| US9745288B2 (en) | 2011-08-16 | 2017-08-29 | Indiana University Research And Technology Corporation | Compounds and methods for treating cancer by inhibiting the urokinase receptor |
| AU2012311504B2 (en) | 2011-09-20 | 2016-03-24 | Cellzome Limited | Pyrazolo[4,3-C]pyridine derivatives as kinase inhibitors |
| AU2012311458B2 (en) | 2011-09-21 | 2016-02-04 | Cellzome Limited | Morpholino substituted urea or carbamate derivatives as mTOR inhibitors |
| EP2763985B1 (en) | 2011-10-07 | 2016-06-22 | Cellzome Limited | {(4-(4-morpholino-dihydrothieno[3,4-d]pyrimidin-2-yl)aryl}urea or carbamate derivatives as mtor inhibitors |
| EA023935B1 (ru) | 2011-10-28 | 2016-07-29 | Новартис Аг | Производные пурина и их применение для лечения заболевания |
| BR112014015723A8 (pt) | 2011-12-23 | 2017-07-04 | Cellzome Ltd | derivados de pirimidino-2,4-diamina como inibidores da quinase |
| AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
| US10213432B2 (en) | 2012-05-16 | 2019-02-26 | Novartis Ag | Dosage regimen for a PI-3 kinase inhibitor |
| KR102172897B1 (ko) | 2012-06-08 | 2020-11-02 | 서트로 바이오파마, 인크. | 부위-특이적 비-천연 아미노산 잔기를 포함하는 항체, 그의 제조 방법 및 그의 사용 방법 |
| DK2863955T3 (en) | 2012-06-26 | 2017-01-23 | Sutro Biopharma Inc | MODIFIED FC PROTEINS, INCLUDING LOCATION-SPECIFIC NON-NATURAL AMINO ACID RESIDUES, CONJUGATES THEREOF, METHODS OF PRODUCING ITS AND PROCEDURES FOR USE THEREOF |
| AU2013302320A1 (en) | 2012-08-17 | 2015-02-26 | Cancer Therapeutics Crc Pty Limited | VEGFR3 inhibitors |
| HK1211208A1 (zh) | 2012-08-22 | 2016-05-20 | Immunogen, Inc. | 細胞毒性苯並二氮呯衍生物 |
| WO2014036022A1 (en) | 2012-08-29 | 2014-03-06 | Amgen Inc. | Quinazolinone compounds and derivatives thereof |
| JP6826367B2 (ja) | 2012-08-31 | 2021-02-03 | ストロ バイオファーマ インコーポレーテッド | アジド基を含む修飾アミノ酸 |
| WO2014041349A1 (en) | 2012-09-12 | 2014-03-20 | Cancer Therapeutics Crc Pty Ltd | Tetrahydropyran-4-ylethylamino- or tetrahydropyranyl-4-ethyloxy-pyrimidines or -pyridazines as isoprenylcysteincarboxymethyl transferase inhibitors |
| WO2014045101A1 (en) | 2012-09-21 | 2014-03-27 | Cellzome Gmbh | Tetrazolo quinoxaline derivatives as tankyrase inhibitors |
| WO2014074517A1 (en) * | 2012-11-08 | 2014-05-15 | Emory University | Cellular compositions used to restore stem cell or progenitor cell function and methods related thereto |
| CN104994879A (zh) | 2013-02-22 | 2015-10-21 | 霍夫曼-拉罗奇有限公司 | 治疗癌症和预防药物抗性的方法 |
| WO2014134483A2 (en) | 2013-02-28 | 2014-09-04 | Immunogen, Inc. | Conjugates comprising cell-binding agents and cytotoxic agents |
| JP6423804B2 (ja) | 2013-02-28 | 2018-11-14 | イミュノジェン・インコーポレーテッド | 細胞結合剤及び細胞毒性剤を含む複合体 |
| HK1213180A1 (zh) | 2013-03-06 | 2016-06-30 | 豪夫迈‧罗氏有限公司 | 治疗和预防癌症药物抗性的方法 |
| BR112015022604A2 (pt) | 2013-03-14 | 2017-10-24 | Genentech Inc | usos de um modulador de modificador de cromatina e um antagonista de egfr |
| AR095443A1 (es) | 2013-03-15 | 2015-10-14 | Fundación Centro Nac De Investig Oncológicas Carlos Iii | Heterociclos condensados con acción sobre atr |
| CA2905123A1 (en) | 2013-03-15 | 2014-09-18 | Genentech, Inc. | Methods of treating cancer and preventing cancer drug resistance |
| WO2014194030A2 (en) | 2013-05-31 | 2014-12-04 | Immunogen, Inc. | Conjugates comprising cell-binding agents and cytotoxic agents |
| US9764039B2 (en) | 2013-07-10 | 2017-09-19 | Sutro Biopharma, Inc. | Antibodies comprising multiple site-specific non-natural amino acid residues, methods of their preparation and methods of their use |
| WO2015031604A1 (en) | 2013-08-28 | 2015-03-05 | Crown Bioscience, Inc. | Gene expression signatures predictive of subject response to a multi-kinase inhibitor and methods of using the same |
| CN103483276B (zh) * | 2013-09-22 | 2018-04-17 | 南京恒道医药科技有限公司 | 一种凡德他尼杂质的制备方法 |
| US9840493B2 (en) | 2013-10-11 | 2017-12-12 | Sutro Biopharma, Inc. | Modified amino acids comprising tetrazine functional groups, methods of preparation, and methods of their use |
| ES2899167T3 (es) | 2013-12-06 | 2022-03-10 | Novartis Ag | Régimen posológico para un inhibidor de fosfatidilinositol 3-cinasas selectivo para la isoforma alfa |
| CA2943329A1 (en) | 2014-03-24 | 2015-10-01 | Genentech, Inc. | Cancer treatment with c-met antagonists and correlation of the latter with hgf expression |
| US11083755B2 (en) | 2015-01-08 | 2021-08-10 | The Board Of Trustees Of The Leland Stanford Junior University | Factors and cells that provide for induction of bone, bone marrow, and cartilage |
| GB201510019D0 (en) | 2015-06-09 | 2015-07-22 | Cancer Therapeutics Crc Pty Ltd | Compounds |
| CN106317022A (zh) * | 2015-06-25 | 2017-01-11 | 中美华世通生物医药科技（武汉）有限公司 | 化合物的制备方法和用途 |
| CN108472289A (zh) | 2015-11-02 | 2018-08-31 | 诺华股份有限公司 | 磷脂酰肌醇3-激酶抑制剂的给药方案 |
| CN105254614B (zh) * | 2015-11-16 | 2017-08-15 | 山东罗欣药业集团股份有限公司 | 一种凡德他尼化合物的合成方法 |
| SG11201806419RA (en) | 2016-01-27 | 2018-08-30 | Sutro Biopharma Inc | Anti-cd74 antibody conjugates, compositions comprising anti-cd74 antibody conjugates and methods of using anti-cd74 antibody conjugates |
| JP2019508405A (ja) | 2016-02-08 | 2019-03-28 | ヴィトリサ セラピューティクス， インコーポレイテッド | 改良された硝子体内半減期を有する組成物およびその使用 |
| CN106349231A (zh) * | 2016-08-09 | 2017-01-25 | 浙江医药高等专科学校 | 一类含卤代噻吩磺酰胺结构的苯并喹唑啉类酪氨酸激酶抑制剂 |
| CN106317039A (zh) * | 2016-08-09 | 2017-01-11 | 浙江医药高等专科学校 | 一种含噻吩磺酰胺结构的乙氧苯并喹唑啉类酪氨酸激酶抑制剂、制备方法及用途 |
| CN106279135A (zh) * | 2016-08-09 | 2017-01-04 | 浙江医药高等专科学校 | 一种噻吩磺酰胺结构的苯并喹唑啉类酪氨酸激酶抑制剂 |
| CN106317040A (zh) * | 2016-08-09 | 2017-01-11 | 浙江医药高等专科学校 | 含噻吩磺酰胺结构的苯并喹唑啉类酪氨酸激酶抑制剂、制备方法及用途 |
| CN106349230A (zh) * | 2016-08-09 | 2017-01-25 | 浙江医药高等专科学校 | 一种含硝基噻吩磺酰胺结构的苯并喹唑啉类酪氨酸激酶抑制剂及用途 |
| CN106397401B (zh) * | 2016-08-30 | 2018-11-13 | 山东罗欣药业集团股份有限公司 | 一种抗癌药物的晶体化合物及其制备方法 |
| CN106478598B (zh) * | 2016-08-30 | 2018-11-13 | 山东罗欣药业集团股份有限公司 | 一种凡德他尼水合物晶体及其制备方法 |
| AU2017321973B2 (en) | 2016-09-02 | 2024-09-05 | Dana-Farber Cancer Institute, Inc. | Composition and methods of treating B cell disorders |
| WO2018060833A1 (en) | 2016-09-27 | 2018-04-05 | Novartis Ag | Dosage regimen for alpha-isoform selective phosphatidylinositol 3-kinase inhibitor alpelisib |
| BR112019011284A2 (pt) | 2016-12-05 | 2019-10-22 | Apros Therapeutics Inc | composto, composição farmacêutica, métodos de tratamento de uma condição, de hbv e de câncer, e, uso de um composto. |
| US10786502B2 (en) | 2016-12-05 | 2020-09-29 | Apros Therapeutics, Inc. | Substituted pyrimidines containing acidic groups as TLR7 modulators |
| DK3558955T3 (da) | 2016-12-22 | 2021-10-25 | Amgen Inc | Benzisothiazol-, isothiazolo[3,4-b]pyridin-, quinazolin-, phthalazin-, pyrido[2,3-d]pyridazin- og pyrido[2,3-d]pyrimidinderivater som kras-g12c-inhibitorer til behandling af lunge-, pankreas- eller kolorektalcancer |
| JOP20190272A1 (ar) | 2017-05-22 | 2019-11-21 | Amgen Inc | مثبطات kras g12c وطرق لاستخدامها |
| WO2019023316A1 (en) | 2017-07-26 | 2019-01-31 | Sutro Biopharma, Inc. | METHODS OF USING ANTI-CD74 ANTIBODIES AND ANTIBODY CONJUGATES IN THE TREATMENT OF A T CELL LYMPHOMA |
| CN111051306B (zh) | 2017-09-08 | 2023-01-03 | 美国安进公司 | Kras g12c的抑制剂及其使用方法 |
| US10596270B2 (en) | 2017-09-18 | 2020-03-24 | Sutro Biopharma, Inc. | Anti-folate receptor antibody conjugates, compositions comprising anti-folate receptor antibody conjugates, and methods of making and using anti-folate receptor antibody conjugates |
| NL2019801B1 (en) | 2017-10-25 | 2019-05-02 | Univ Leiden | Delivery vectors |
| US11045484B2 (en) | 2018-05-04 | 2021-06-29 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
| JP7266043B2 (ja) | 2018-05-04 | 2023-04-27 | アムジエン・インコーポレーテツド | ＫＲａｓ Ｇ１２Ｃ阻害剤及びそれを使用する方法 |
| CA3099045A1 (en) | 2018-05-10 | 2019-11-14 | Amgen Inc. | Kras g12c inhibitors for the treatment of cancer |
| CA3098885A1 (en) | 2018-06-01 | 2019-12-05 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| EP3802519A1 (en) | 2018-06-04 | 2021-04-14 | Apros Therapeutics, Inc. | Pyrimidine compounds containing acidic groups useful to treat diseases connected to the modulation of tlr7 |
| CA3099799A1 (en) | 2018-06-11 | 2019-12-19 | Amgen Inc. | Kras g12c inhibitors for treating cancer |
| US11285156B2 (en) | 2018-06-12 | 2022-03-29 | Amgen Inc. | Substituted piperazines as KRAS G12C inhibitors |
| GB201810092D0 (en) | 2018-06-20 | 2018-08-08 | Ctxt Pty Ltd | Compounds |
| GB201810581D0 (en) | 2018-06-28 | 2018-08-15 | Ctxt Pty Ltd | Compounds |
| EP3852811A1 (en) | 2018-09-17 | 2021-07-28 | Sutro Biopharma, Inc. | Combination therapies with anti-folate receptor antibody conjugates |
| JP7516029B2 (ja) | 2018-11-16 | 2024-07-16 | アムジエン・インコーポレーテツド | Ｋｒａｓ ｇ１２ｃ阻害剤化合物の重要な中間体の改良合成法 |
| JP7377679B2 (ja) | 2018-11-19 | 2023-11-10 | アムジエン・インコーポレーテツド | がん治療のためのｋｒａｓｇ１２ｃ阻害剤及び１種以上の薬学的に活性な追加の薬剤を含む併用療法 |
| MA55136A (fr) | 2018-11-19 | 2022-02-23 | Amgen Inc | Inhibiteurs de kras g12c et leurs procédés d'utilisation |
| AU2019401495B2 (en) | 2018-12-20 | 2025-06-26 | Amgen Inc. | Heteroaryl amides useful as KIF18A inhibitors |
| CA3123227A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
| EP3897855B1 (en) | 2018-12-20 | 2023-06-07 | Amgen Inc. | Kif18a inhibitors |
| CR20210387A (es) | 2018-12-20 | 2021-08-19 | Amgen Inc | Inhibidores de kif18a |
| SG11202106635WA (en) | 2018-12-21 | 2021-07-29 | Daiichi Sankyo Co Ltd | Combination of antibody-drug conjugate and kinase inhibitor |
| MX2021010323A (es) | 2019-03-01 | 2021-12-10 | Revolution Medicines Inc | Compuestos bicíclicos de heterociclilo y usos de este. |
| WO2020180768A1 (en) | 2019-03-01 | 2020-09-10 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
| CA3130727A1 (en) | 2019-03-28 | 2020-10-01 | Amplia Therapeutics Limited | A salt and crystal form of a fak inhibitor |
| EP3962951A1 (en) | 2019-05-03 | 2022-03-09 | Sutro Biopharma, Inc. | Anti-bcma antibody conjugates |
| EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
| JOP20210310A1 (ar) | 2019-05-21 | 2023-01-30 | Amgen Inc | أشكال الحالة الصلبة |
| US20220281843A1 (en) | 2019-08-02 | 2022-09-08 | Amgen Inc. | Kif18a inhibitors |
| JP7699100B2 (ja) | 2019-08-02 | 2025-06-26 | アムジエン・インコーポレーテツド | Ｋｉｆ１８ａ阻害剤 |
| AU2020325115A1 (en) | 2019-08-02 | 2022-03-17 | Amgen Inc. | Pyridine derivatives as KIF18A inhibitors |
| US20220289724A1 (en) | 2019-08-02 | 2022-09-15 | Amgen Inc. | Kif18a inhibitors |
| CA3152674A1 (en) | 2019-08-31 | 2021-03-04 | Etern Biopharma (Shanghai) Co., Ltd. | Pyrazole derivatives for fgfr inhibitor and preparation method thereof |
| WO2021081212A1 (en) | 2019-10-24 | 2021-04-29 | Amgen Inc. | Pyridopyrimidine derivatives useful as kras g12c and kras g12d inhibitors in the treatment of cancer |
| AU2020379734B2 (en) | 2019-11-04 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
| KR20220109407A (ko) | 2019-11-04 | 2022-08-04 | 레볼루션 메디슨즈, 인크. | Ras 억제제 |
| WO2021091967A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
| BR112022008858A2 (pt) | 2019-11-08 | 2022-09-06 | Revolution Medicines Inc | Composto, composição farmacêutica e métodos para inibir sos1 em um sujeito, para inibir a interação de sos1 e uma proteína, para tratar ou prevenir uma doença e para tratar ou prevenir câncer |
| JP2023501528A (ja) | 2019-11-14 | 2023-01-18 | アムジエン・インコーポレーテツド | Ｋｒａｓ ｇ１２ｃ阻害剤化合物の改善された合成 |
| AU2020383535A1 (en) | 2019-11-14 | 2022-05-05 | Amgen Inc. | Improved synthesis of KRAS G12C inhibitor compound |
| JP2023505100A (ja) | 2019-11-27 | 2023-02-08 | レボリューション メディシンズ インコーポレイテッド | 共有ｒａｓ阻害剤及びその使用 |
| CN114929279A (zh) | 2020-01-07 | 2022-08-19 | 锐新医药公司 | Shp2抑制剂给药和治疗癌症的方法 |
| US20230095053A1 (en) | 2020-03-03 | 2023-03-30 | Sutro Biopharma, Inc. | Antibodies comprising site-specific glutamine tags, methods of their preparation and methods of their use |
| CA3183032A1 (en) | 2020-06-18 | 2021-12-23 | Mallika Singh | Methods for delaying, preventing, and treating acquired resistance to ras inhibitors |
| WO2022053130A1 (en) | 2020-09-09 | 2022-03-17 | Sid Alex Group, S.R.O. | Antago-mir-155 for treatment of v-src, c-src-tyrosine kinase-induced cancers |
| US11690915B2 (en) | 2020-09-15 | 2023-07-04 | Revolution Medicines, Inc. | Ras inhibitors |
| TW202241885A (zh) | 2020-12-22 | 2022-11-01 | 大陸商上海齊魯銳格醫藥研發有限公司 | Ｓｏｓ１抑制劑及其用途 |
| CA3217920A1 (en) | 2021-05-05 | 2022-11-10 | Andreas BUCKL | Ras inhibitors for the treatment of cancer |
| MX2023013085A (es) | 2021-05-05 | 2023-11-16 | Revolution Medicines Inc | Inhibidores de ras. |
| WO2022235866A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| EP4448526A1 (en) | 2021-12-17 | 2024-10-23 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| KR20230131448A (ko) | 2022-03-04 | 2023-09-13 | 주식회사 파노로스바이오사이언스 | VEGF-Grab 및 PD-1 또는 PD-L1 길항제를 포함하는 병용 투여용 조성물 |
| US20250188036A1 (en) | 2022-03-07 | 2025-06-12 | Amgen Inc. | A process for preparing 4-methyl-2-propan-2-yl-pyridine-3-carbonitrile |
| CN119136806A (zh) | 2022-03-08 | 2024-12-13 | 锐新医药公司 | 用于治疗免疫难治性肺癌的方法 |
| AU2023274540A1 (en) | 2022-05-24 | 2024-12-12 | Daiichi Sankyo Company, Limited | Dosage regimen of an anti-cdh6 antibody-drug conjugate |
| EP4536364A1 (en) | 2022-06-10 | 2025-04-16 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| CN120076831A (zh) | 2022-06-30 | 2025-05-30 | 苏特罗生物制药公司 | 抗ror1抗体和抗体缀合物、包含抗ror1抗体或抗体缀合物的组合物、以及制备和使用抗ror1抗体和抗体缀合物的方法 |
| CR20250141A (es) | 2022-10-14 | 2025-05-26 | Black Diamond Therapeutics Inc | Métodos de tratamiento del cáncer usando derivados de isoquinolina o 6-aza-quinolina |
| AU2024241633A1 (en) | 2023-03-30 | 2025-11-06 | Revolution Medicines, Inc. | Compositions for inducing ras gtp hydrolysis and uses thereof |
| AR132338A1 (es) | 2023-04-07 | 2025-06-18 | Revolution Medicines Inc | Inhibidores de ras |
| AU2024243852A1 (en) | 2023-04-07 | 2025-11-06 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| WO2024216016A1 (en) | 2023-04-14 | 2024-10-17 | Revolution Medicines, Inc. | Crystalline forms of a ras inhibitor |
| WO2024216048A1 (en) | 2023-04-14 | 2024-10-17 | Revolution Medicines, Inc. | Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ｒａｓ相關疾病或病症之組合療法 |
| WO2025034702A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Rmc-6291 for use in the treatment of ras protein-related disease or disorder |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025081117A2 (en) | 2023-10-13 | 2025-04-17 | Sutro Biopharma, Inc. | Anti-tissue factor antibodies and antibody conjugates, compositions comprising anti-tissue factor antibodies or antibody conjugates, and methods of making and using anti-tissue factor antibodies and antibody conjugates |
| WO2025137507A1 (en) | 2023-12-22 | 2025-06-26 | Regor Pharmaceuticals, Inc. | Sos1 inhibitors and uses thereof |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
Family Cites Families (126)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3266990A (en) | 1963-09-24 | 1966-08-16 | Warner Lambert Pharmaceutical | Derivatives of quinazoline |
| US3870725A (en) | 1971-03-30 | 1975-03-11 | Lilly Industries Ltd | Nitrothiazole derivatives |
| JPS542327A (en) | 1977-06-07 | 1979-01-09 | Sankyo Co Ltd | Agricultural and horticultural pesticide |
| JPS5538325A (en) | 1978-09-11 | 1980-03-17 | Sankyo Co Ltd | 4-anilinoquinazoline derivative and its preparation |
| US4343940A (en) | 1979-02-13 | 1982-08-10 | Mead Johnson & Company | Anti-tumor quinazoline compounds |
| GB2160201B (en) | 1984-06-14 | 1988-05-11 | Wyeth John & Brother Ltd | Quinazoline and cinnoline derivatives |
| IL81307A0 (en) | 1986-01-23 | 1987-08-31 | Union Carbide Agricult | Method for reducing moisture loss from plants and increasing crop yield utilizing nitrogen containing heterocyclic compounds and some novel polysubstituted pyridine derivatives |
| EP0326307B1 (en) | 1988-01-23 | 1994-08-17 | Kyowa Hakko Kogyo Co., Ltd. | Novel pyridazinone derivatives and pharmaceutical preparations containing them |
| IL89029A (en) | 1988-01-29 | 1993-01-31 | Lilly Co Eli | Fungicidal quinoline and cinnoline derivatives, compositions containing them, and fungicidal methods of using them |
| US5411963A (en) | 1988-01-29 | 1995-05-02 | Dowelanco | Quinazoline derivatives |
| ES2071484T3 (es) | 1991-02-20 | 1995-06-16 | Pfizer | Derivados de 2,4-diaminoquinazolinas para aumentar la actividad antitumoral. |
| WO1992016527A1 (fr) | 1991-03-22 | 1992-10-01 | Nippon Soda Co., Ltd. | Derive de pyridine substitue en position 2, sa production, et bactericide d'agrohorticulture |
| US6645969B1 (en) | 1991-05-10 | 2003-11-11 | Aventis Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase |
| US5721237A (en) | 1991-05-10 | 1998-02-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Protein tyrosine kinase aryl and heteroaryl quinazoline compounds having selective inhibition of HER-2 autophosphorylation properties |
| US5710158A (en) | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| SG64322A1 (en) | 1991-05-10 | 1999-04-27 | Rhone Poulenc Rorer Int | Bis mono and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase |
| US5714493A (en) | 1991-05-10 | 1998-02-03 | Rhone-Poulenc Rorer Pharmaceuticals, Inc. | Aryl and heteroaryl quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase |
| US5480883A (en) | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| NZ243082A (en) | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
| GB9300059D0 (en) | 1992-01-20 | 1993-03-03 | Zeneca Ltd | Quinazoline derivatives |
| DE4208254A1 (de) | 1992-03-14 | 1993-09-16 | Hoechst Ag | Substituierte pyrimidine, verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel und fungizid |
| US5270466A (en) | 1992-06-11 | 1993-12-14 | American Cyanamid Company | Substituted quinazoline fungicidal agents |
| US5712395A (en) | 1992-11-13 | 1998-01-27 | Yissum Research Development Corp. | Compounds for the treatment of disorders related to vasculogenesis and/or angiogenesis |
| 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 |
| US5792771A (en) | 1992-11-13 | 1998-08-11 | Sugen, Inc. | Quinazoline compounds and compositions thereof for the treatment of disease |
| GB9323290D0 (en) | 1992-12-10 | 1994-01-05 | Zeneca Ltd | Quinazoline derivatives |
| GB9314884D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Tricyclic derivatives |
| GB9314893D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
| WO1995006648A1 (fr) | 1993-09-03 | 1995-03-09 | Kyowa Hakko Kogyo Co., Ltd. | Derive d'imidazoquinazoline |
| JPH07126165A (ja) | 1993-10-29 | 1995-05-16 | Masao Oguro | 腫瘍治療剤 |
| US5656643A (en) | 1993-11-08 | 1997-08-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| GB9325217D0 (en) | 1993-12-09 | 1994-02-09 | Zeneca Ltd | Pyrimidine derivatives |
| US5700823A (en) | 1994-01-07 | 1997-12-23 | Sugen, Inc. | Treatment of platelet derived growth factor related disorders such as cancers |
| IL112248A0 (en) | 1994-01-25 | 1995-03-30 | Warner Lambert Co | Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them |
| IL112249A (en) | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
| JP2890267B2 (ja) | 1994-02-23 | 1999-05-10 | ファイザー インク． | ４−ヘテロサイクリル−置換キナゾリン誘導体、その調製法および抗癌剤としてのその使用法 |
| WO1995024190A2 (en) | 1994-03-07 | 1995-09-14 | Sugen, Inc. | Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof |
| DK0682027T3 (da) | 1994-05-03 | 1998-05-04 | Ciba Geigy Ag | Pyrrolopyrimidinderivater med antiproliferativ virkning |
| DE19503151A1 (de) | 1995-02-01 | 1996-08-08 | Thomae Gmbh Dr K | Pyrimido[5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| TW414798B (en) | 1994-09-07 | 2000-12-11 | Thomae Gmbh Dr K | Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation |
| GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
| TW321649B (forum.php) | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
| GB9424233D0 (en) | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
| WO1996029331A1 (de) | 1995-03-20 | 1996-09-26 | Dr. Karl Thomae Gmbh | Imidazochinazoline, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| IL117620A0 (en) | 1995-03-27 | 1996-07-23 | Fujisawa Pharmaceutical Co | Heterocyclic compounds processes for the preparation thereof and pharmaceutical compositions containing the same |
| EP0817775B1 (en) | 1995-03-30 | 2001-09-12 | Pfizer Inc. | Quinazoline derivatives |
| ES2150113T3 (es) | 1995-04-03 | 2000-11-16 | Novartis Ag | Derivados de pirazol y procedimientos para la preparacion de los mismos. |
| GB9508537D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| GB9508535D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivative |
| WO1996033977A1 (en) | 1995-04-27 | 1996-10-31 | Zeneca Limited | Quinazoline derivatives |
| GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| GB9508565D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quiazoline derivative |
| IL117923A (en) | 1995-05-03 | 2000-06-01 | Warner Lambert Co | Anti-cancer pharmaceutical compositions containing polysubstituted pyrido¬2,3-d¾pyrimidine derivatives and certain such novel compounds |
| US6020492A (en) | 1995-05-12 | 2000-02-01 | Neurogen Corporation | Deazapurine derivatives; a new class of CRF1 specific ligands |
| TW334434B (en) | 1995-05-16 | 1998-06-21 | Kanebo Ltd | Novel quinazoline compound and anti-tumor agent |
| US5639757A (en) | 1995-05-23 | 1997-06-17 | Pfizer Inc. | 4-aminopyrrolo[2,3-d]pyrimidines as tyrosine kinase inhibitors |
| US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
| US5773459A (en) | 1995-06-07 | 1998-06-30 | Sugen, Inc. | Urea- and thiourea-type compounds |
| EP0832073B1 (en) | 1995-06-07 | 2002-01-16 | Sugen, Inc. | Quinazolines and pharmaceutical compositions |
| US5650415A (en) | 1995-06-07 | 1997-07-22 | Sugen, Inc. | Quinoline compounds |
| CA2223081C (en) | 1995-06-07 | 2001-03-06 | Pfizer Inc. | Heterocyclic ring-fused pyrimidine derivatives |
| SI9620103A (sl) | 1995-07-06 | 1998-10-31 | Novartis Ag | Pirolopirimidini in postopki za njihovo pripravo |
| GB9514265D0 (en) | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
| AR004010A1 (es) | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
| GB9520822D0 (en) | 1995-10-11 | 1995-12-13 | Wellcome Found | Therapeutically active compounds |
| UA57002C2 (uk) | 1995-10-13 | 2003-06-16 | Мерк Фросст Кенада Енд Ко./Мерк Фросст Кенада Енд Сі. | Похідне (метилсульфоніл)феніл-2-(5н)-фуранону, фармацевтична композиція та спосіб лікування |
| JP3337477B2 (ja) | 1995-10-30 | 2002-10-21 | メルク フロスト カナダ アンド カンパニー | Ｃｏｘ−２阻害剤のプロドラッグとしての３，４−ジアリール−２−ヒドロキシ−２，５−ジヒドロフラン |
| US6143764A (en) | 1995-11-07 | 2000-11-07 | Kirin Beer Kabushiki Kaisha | Quinoline and quinazoline derivatives inhibiting platelet-derived growth factor receptor autophosphorylation and pharmaceutical compositions containing the same |
| ATE201873T1 (de) | 1995-11-14 | 2001-06-15 | Pharmacia & Upjohn Spa | Aryl- und heteroaryl- purin- und pyridopyrimidin- derivate |
| GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| CH690773A5 (de) | 1996-02-01 | 2001-01-15 | Novartis Ag | Pyrrolo(2,3-d)pyrimide und ihre Verwendung. |
| US5760041A (en) | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
| KR19990082463A (ko) * | 1996-02-13 | 1999-11-25 | 돈 리사 로얄 | 혈관 내피 성장 인자 억제제로서의 퀴나졸린유도체 |
| GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| GB9603097D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline compounds |
| GB9604361D0 (en) | 1996-02-29 | 1996-05-01 | Pharmacia Spa | 4-Substituted pyrrolopyrimidine compounds as tyrosine kinase inhibitors |
| NZ331191A (en) * | 1996-03-05 | 2000-03-27 | Zeneca Ltd | 4-anilinoquinazoline derivatives and pharmaceutical compositions thereof |
| DE19608653A1 (de) | 1996-03-06 | 1997-09-11 | Thomae Gmbh Dr K | Pyrimido[5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE19608631A1 (de) | 1996-03-06 | 1997-09-11 | Thomae Gmbh Dr K | 4-Amino-pyrimidin-Derivate, diese Verbindungen enthaltende Arnzeimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE19608588A1 (de) | 1996-03-06 | 1997-09-11 | Thomae Gmbh Dr K | Pyrimido [5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE19629652A1 (de) | 1996-03-06 | 1998-01-29 | Thomae Gmbh Dr K | 4-Amino-pyrimidin-Derivate, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| AU2103097A (en) | 1996-03-15 | 1997-10-10 | Zeneca Limited | Cinnoline derivatives and use as medicine |
| AU5533996A (en) | 1996-04-04 | 1997-10-29 | University Of Nebraska Board Of Regents | Synthetic triple helix-forming compounds |
| CN1923818A (zh) | 1996-04-12 | 2007-03-07 | 沃尼尔·朗伯公司 | 酪氨酸激酶的不可逆抑制剂 |
| GB9607729D0 (en) | 1996-04-13 | 1996-06-19 | Zeneca Ltd | Quinazoline derivatives |
| DE19614718A1 (de) | 1996-04-15 | 1997-10-16 | Hoechst Schering Agrevo Gmbh | Substituierte Pyridine/Pyrimidine, Verfahren zu ihrer Herstellung, und ihre Verwendung als Schädlingsbekämpfungsmittel |
| GB9707800D0 (en) | 1996-05-06 | 1997-06-04 | Zeneca Ltd | Chemical compounds |
| GB9613021D0 (en) | 1996-06-21 | 1996-08-28 | Pharmacia Spa | Bicyclic 4-aralkylaminopyrimidine derivatives as tyrosine kinase inhibitors |
| JP2000512990A (ja) | 1996-06-24 | 2000-10-03 | ファイザー・インク | 過増殖性疾患を処置するためのフェニルアミノ置換三環式誘導体 |
| CZ8799A3 (cs) | 1996-07-13 | 1999-06-16 | Glaxo Group Limited | Bicyklické heteroaromatické sloučeniny, způsob jejich výroby a farmaceutický prostředek |
| HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| ID19609A (id) | 1996-07-13 | 1998-07-23 | Glaxo Group Ltd | Senyawa-senyawa heterosiklik |
| PT938486E (pt) | 1996-08-23 | 2008-03-27 | Novartis Ag | Pirrolopirimidinas substituídas e processos para a sua preparação |
| WO1998010767A2 (en) | 1996-09-13 | 1998-03-19 | Sugen, Inc. | Use of quinazoline derivatives for the manufacture of a medicament in the treatment of hyperproliferative skin disorders |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| CA2263479A1 (en) | 1996-09-25 | 1998-04-02 | Zeneca Limited | Quinoline derivatives inhibiting the effect of growth factors such as vegf |
| KR100622323B1 (ko) | 1996-10-01 | 2006-11-30 | 교와 핫꼬 고교 가부시끼가이샤 | 질소-함유헤테로고리화합물 |
| EP0837063A1 (en) | 1996-10-17 | 1998-04-22 | Pfizer Inc. | 4-Aminoquinazoline derivatives |
| WO1998023613A1 (en) | 1996-11-27 | 1998-06-04 | Pfizer Inc. | Fused bicyclic pyrimidine derivatives |
| CO4950519A1 (es) | 1997-02-13 | 2000-09-01 | Novartis Ag | Ftalazinas, preparaciones farmaceuticas que las comprenden y proceso para su preparacion |
| US6002008A (en) | 1997-04-03 | 1999-12-14 | American Cyanamid Company | Substituted 3-cyano quinolines |
| UA73073C2 (uk) | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
| ATE241986T1 (de) | 1997-05-06 | 2003-06-15 | Wyeth Corp | Verwendung von chinazolin verbindungen zur behandlung von polyzystischer nierenkrankheit |
| US5929080A (en) | 1997-05-06 | 1999-07-27 | American Cyanamid Company | Method of treating polycystic kidney disease |
| ZA986732B (en) | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitiors of tyrosine kinases |
| ZA986729B (en) | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitors of tyrosine kinases |
| TW436485B (en) | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
| AR016817A1 (es) | 1997-08-14 | 2001-08-01 | Smithkline Beecham Plc | Derivados de fenilurea o feniltiourea, procedimiento para su preparacion, coleccion de compuestos, compuestos intermediarios, composicion farmaceutica,metodo de tratamiento y uso de dichos compuestos para la manufactura de un medicamento |
| US6294532B1 (en) | 1997-08-22 | 2001-09-25 | Zeneca Limited | Oxindolylquinazoline derivatives as angiogenesis inhibitors |
| DE19742379C1 (de) * | 1997-09-25 | 1999-02-11 | Siemens Ag | Verfahren zum Betrieb eines Ultraschall-Therapiegeräts sowie entsprechendes Gerät |
| DK1119567T3 (da) | 1998-10-08 | 2005-07-25 | Astrazeneca Ab | Quinazolinderivater |
| CZ306810B6 (cs) | 1999-02-10 | 2017-07-19 | Astrazeneca Ab | Použití chinazolinového derivátu jako inhibitoru angiogeneze |
| US20030086924A1 (en) * | 1999-06-25 | 2003-05-08 | Genentech, Inc. | Treatment with anti-ErbB2 antibodies |
| SI1676845T1 (sl) | 1999-11-05 | 2008-10-31 | Astrazeneca Ab | Novi kinazolinski derivati |
| DE60112268T2 (de) | 2000-03-06 | 2006-05-24 | Astrazeneca Ab | Verwendung von quinazolinderivate als inhibitoren der angiogenese |
| GB0008269D0 (en) | 2000-04-05 | 2000-05-24 | Astrazeneca Ab | Combination chemotherapy |
| DE60121931T2 (de) | 2000-04-07 | 2007-03-01 | Astrazeneca Ab | Chinazolinverbindungen |
| WO2002012227A2 (en) | 2000-08-09 | 2002-02-14 | Astrazeneca Ab | Indole, azaindole and indazole derivatives having vegf inhibiting activity |
| AU2001276536B2 (en) | 2000-08-09 | 2007-01-04 | Astrazeneca Ab | Quinoline derivatives having vegf inhibiting activity |
| CA2415022A1 (en) | 2000-08-09 | 2002-02-14 | Astrazeneca Ab | Cinnoline compounds |
| GB0126879D0 (en) | 2001-11-08 | 2002-01-02 | Astrazeneca Ab | Combination therapy |
| US7268230B2 (en) | 2002-02-01 | 2007-09-11 | Astrazeneca Ab | Quinazoline compounds |
| GB0218526D0 (en) | 2002-08-09 | 2002-09-18 | Astrazeneca Ab | Combination therapy |
| BR0313116A (pt) | 2002-08-09 | 2005-07-05 | Astrazeneca Ab | Método para a produção de um efeito redutor de permeabilidade vascular e/ou antiangiogênico em um animal de sangue quente tal como um humano, método para o tratamento de um câncer em um animal de sangue quente tal como humano, e, uso de zd6474 ou de um seu sal farmaceuticamente aceitável. |
| GB0223380D0 (en) | 2002-10-09 | 2002-11-13 | Astrazeneca Ab | Combination therapy |
| DE602004032310D1 (de) | 2003-02-13 | 2011-06-01 | Astrazeneca Ab | Kombinationstherapie von zd6474 mit 5-fu oder/und cpt-11 |
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