TWI654979B - 使用tor激酶抑制劑組合療法以治療癌症之方法 - Google Patents
使用tor激酶抑制劑組合療法以治療癌症之方法 Download PDFInfo
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- TWI654979B TWI654979B TW103113959A TW103113959A TWI654979B TW I654979 B TWI654979 B TW I654979B TW 103113959 A TW103113959 A TW 103113959A TW 103113959 A TW103113959 A TW 103113959A TW I654979 B TWI654979 B TW I654979B
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Classifications
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Engineering & Computer Science (AREA)
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- Endocrinology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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| US201361908408P | 2013-11-25 | 2013-11-25 | |
| US61/908,408 | 2013-11-25 |
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| PT2066656E (pt) | 2006-09-26 | 2012-06-28 | Celgene Corp | Derivados de quinazolina substituídos em 5 como agentes antitumorais |
| CA3037184C (en) | 2011-03-11 | 2021-04-06 | Celgene Corporation | Solid forms of 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)-piperidine-2,6-dione, and their pharmaceutical compositions and uses |
| US9682952B2 (en) | 2012-09-04 | 2017-06-20 | Celgene Corporation | Isotopologues of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl) piperidine-2-6-dione and methods of preparation thereof |
| US9126950B2 (en) | 2012-12-21 | 2015-09-08 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| MX364101B (es) | 2013-04-17 | 2019-04-12 | Signal Pharm Llc | Terapia de combinación que comprende un compuesto de dihidropirazino-pirazina y un antagonista de receptor de andrógenos para tratar cáncer de próstata. |
| EA030808B1 (ru) | 2013-04-17 | 2018-09-28 | СИГНАЛ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | ПРИМЕНЕНИЕ 1-ЭТИЛ-7-(2-МЕТИЛ-6-(1Н-1,2,4-ТРИАЗОЛ-3-ИЛ)ПИРИДИН-3-ИЛ)-3,4-ДИГИДРОПИРАЗИНО[2,3-b]ПИРАЗИН-2(1Н)-ОНА В ЛЕЧЕНИИ МУЛЬТИФОРМНОЙ ГЛИОБЛАСТОМЫ |
| TW201526897A (zh) * | 2013-04-17 | 2015-07-16 | Signal Pharm Llc | 使用tor激酶抑制劑組合療法以治療癌症之方法 |
| HK1221150A1 (zh) | 2013-04-17 | 2017-05-26 | 西格诺药品有限公司 | 用二氢吡嗪并-吡嗪类对癌症的治疗 |
| SG11201508527VA (en) * | 2013-04-17 | 2015-11-27 | Signal Pharm Llc | Pharmaceutical formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl) pyridin-3-yl) -3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one |
| CA3143529A1 (en) | 2013-05-29 | 2014-12-04 | Signal Pharmaceuticals, Llc | Pharmaceutical compositions 0f 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino [2,3-b]pyrazin-2(1h)-one, a solid form thereof and methods of their use |
| US9415049B2 (en) | 2013-12-20 | 2016-08-16 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| US9737535B2 (en) | 2014-04-16 | 2017-08-22 | Signal Pharmaceuticals, Llc | Methods for treating cancer using TOR kinase inhibitor combination therapy comprising administering substituted pyrazino[2,3-b]pyrazines |
| NZ714742A (en) | 2014-04-16 | 2017-04-28 | Signal Pharm Llc | Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use |
| WO2015160880A1 (en) | 2014-04-16 | 2015-10-22 | Signal Pharmaceuticals, Llc | SOLID FORMS COMPRISING 1-ETHYL-7-(2-METHYL-6-(1H-1,2,4-TRIAZOL-3-YL) PYRIDIN-3-YL)-3,4-DIHYDROPYRAZINO(2,3-b)PYRAZIN-2(1H)-ONE, AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF |
| MX2017000366A (es) * | 2014-07-11 | 2017-04-27 | Celgene Corp | Terapia de combinacion para el cancer. |
| JP6871919B2 (ja) | 2015-06-16 | 2021-05-19 | ナノファギックス エルエルシー | 薬物送達及びイメージング化学コンジュゲート、製剤及びその使用方法 |
| MY198676A (en) | 2017-06-22 | 2023-09-15 | Celgene Corp | Treatment of hepatocellular carcinoma characterized by hepatitis b virus infection |
| CN112313236A (zh) * | 2018-03-30 | 2021-02-02 | 拜欧斯瑞克斯公司 | 噻吩并嘧啶酮化合物 |
| KR102862736B1 (ko) * | 2022-12-07 | 2025-09-22 | 부산대학교 산학협력단 | 신규 2-((트랜스-4-(4-아릴옥시)사이클로헥실)아미노)퀴나졸리논 유도체 및 이의 제조방법 |
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|---|---|---|---|---|
| CN102245611A (zh) * | 2008-10-27 | 2011-11-16 | 西格诺药品有限公司 | 用于与 mTOR/PI3K/AKT/途径相关的肿瘤适应症和疾病的 mTOR激酶抑制剂 |
| US20120230983A1 (en) * | 2011-03-11 | 2012-09-13 | Muller George W | Methods of treating cancer using 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)-piperidine-2,6-dione |
Family Cites Families (141)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3507866A (en) | 1967-08-08 | 1970-04-21 | Merck & Co Inc | 1h - imidazo(4,5-b)pyrazin - 2 - one and processes for their preparation |
| US3567725A (en) | 1968-11-20 | 1971-03-02 | Merck & Co Inc | Process for preparation of 1h-imidazo-(4,5-b)pyrazin-2-ones |
| US4294836A (en) | 1980-03-24 | 1981-10-13 | Sterling Drug Inc. | 1,3-Dihydro-6-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones and -imidazo[4,5-b]-pyridine-2-thiones and their cardiotonic use |
| US4294837A (en) | 1980-03-28 | 1981-10-13 | Sterling Drug Inc. | 1,3-Dihydro-6-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones and -imidazo[4,5-b]pyridine-2-thiones and their cardiotonic use |
| US4317909A (en) | 1980-03-24 | 1982-03-02 | Sterling Drug Inc. | Preparation of 1,3-dihydro-5-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones |
| US4309537A (en) | 1980-03-28 | 1982-01-05 | Sterling Drug Inc. | Production of imidazo[4,5-b]pyridin-2-ones or thiones |
| GB8709448D0 (en) | 1987-04-21 | 1987-05-28 | Pfizer Ltd | Heterobicyclic quinoline derivatives |
| JPS63275582A (ja) | 1987-05-02 | 1988-11-14 | Naade Kenkyusho:Kk | 2−アミノイミダゾ〔4,5−b〕ピリジン誘導体の製造方法 |
| DD262026A1 (de) | 1987-07-10 | 1988-11-16 | Akad Wissenschaften Ddr | Verfahren zur herstellung von 4-substituierten 6-(pyrid-4-yl)-2,4-dihydro-1h-imidazo[4,5-b]pyrid-2-onen |
| FR2643903A1 (fr) | 1989-03-03 | 1990-09-07 | Union Pharma Scient Appl | Nouveaux derives de benzimidazole, leurs procedes de preparation, intermediaires de synthese, compositions pharmaceutiques les contenant, utiles notamment pour le traitement des maladies cardiovasculaires, et des ulceres duodenaux |
| US4963561A (en) | 1990-02-28 | 1990-10-16 | Sterling Drug Inc. | Imidazopyridines, their preparation and use |
| TW274550B (enExample) | 1992-09-26 | 1996-04-21 | Hoechst Ag | |
| DE19601627A1 (de) | 1996-01-18 | 1997-07-24 | Bayer Ag | Heteroatomhaltige Cyclopentanopyridyl-Oxazolidinone |
| US6031105A (en) | 1996-04-09 | 2000-02-29 | Pfizer Inc | Substituted pyridines |
| ATE281834T1 (de) | 1997-09-26 | 2004-11-15 | Zentaris Gmbh | Azabenzimidazol-verbindungen zur modulation der serin/threonin protein-kinase funktion |
| AU750564B2 (en) | 1997-11-27 | 2002-07-25 | Chugai Seiyaku Kabushiki Kaisha | Examination method, examination reagent and remedy for diseases caused by variation in LKB1 gene |
| ZA9810490B (en) | 1997-12-03 | 1999-05-20 | Dainippon Pharmaceutical Co | 2-Aryl-8-oxodihydropurine derivative process for the preparation thereof pharmaceutical composition containing the same and intermediate therefor |
| EP1186232A4 (en) | 1999-05-31 | 2004-11-10 | Chugai Pharmaceutical Co Ltd | 'KNOCKOUT' ANIMALS LACKING THE LKB1 GENE |
| JP2003146987A (ja) | 1999-05-31 | 2003-05-21 | Dainippon Pharmaceut Co Ltd | 2−アリールプリン−9−アセトアミド誘導体 |
| JP3814125B2 (ja) | 1999-06-02 | 2006-08-23 | 大日本住友製薬株式会社 | 2−アリール−8−オキソジヒドロプリン誘導体からなる医薬 |
| JP2002100363A (ja) | 2000-09-25 | 2002-04-05 | Mitsubishi Chemicals Corp | リチウム二次電池用正極材料、リチウム二次電池用正極及びリチウム二次電池 |
| JP2002167387A (ja) | 2000-11-29 | 2002-06-11 | Dainippon Pharmaceut Co Ltd | 2−(7,8−ジヒドロ−8−オキソ−9h−プリン−9−イル)酢酸誘導体 |
| ES2249384T3 (es) | 2000-12-12 | 2006-04-01 | Neurogen Corporation | Espiro(isobenzofuran-1,4'-piperadin)-3-onas y 3h-espirobenzofuran-1,4-piperidinas. |
| WO2002076954A1 (en) | 2001-03-23 | 2002-10-03 | Smithkline Beecham Corporation | Compounds useful as kinase inhibitors for the treatment of hyperproliferative diseases |
| NZ531928A (en) | 2001-09-04 | 2005-10-28 | Boehringer Ingelheim Pharma | Novel dihydropteridinones, method for producing the same and the use thereof as medicaments |
| US6825184B2 (en) | 2001-10-18 | 2004-11-30 | Boehringer Ingelheim Pharmaceuticals, Inc. | 1,4-Disubstituted benzo-fused urea compounds |
| CN100522999C (zh) | 2002-02-14 | 2009-08-05 | 免疫医疗公司 | 抗cd20抗体及其融合蛋白和使用方法 |
| MY156407A (en) | 2002-02-28 | 2016-02-26 | Novartis Ag | 5-phenylthiazole derivatives and use as p13 kinase inhibitors |
| US7247621B2 (en) | 2002-04-30 | 2007-07-24 | Valeant Research & Development | Antiviral phosphonate compounds and methods therefor |
| CA2484921A1 (en) | 2002-05-06 | 2003-11-13 | Genelabs Technologies, Inc. | Nucleoside derivatives for treating hepatitis c virus infection |
| WO2004042002A2 (en) | 2002-08-05 | 2004-05-21 | University Of Massachusetts | Compounds for modulating rna interference |
| US7199119B2 (en) | 2002-10-31 | 2007-04-03 | Amgen Inc. | Antiinflammation agents |
| EP2316831B1 (en) | 2002-11-21 | 2013-03-06 | Novartis AG | 2-(morpholin-4-yl)pyrimidines as phosphotidylinositol (PI) 3-kinase inhibitors and their use in the treatment of cancer |
| MXPA05007503A (es) | 2003-01-17 | 2005-09-21 | Warner Lambert Co | Heterociclicos 2-aminopiridina sustituidos como inhibidores de proliferacion celular. |
| MXPA05009068A (es) | 2003-02-26 | 2005-10-19 | Boehringer Ingelheim Pharma | Dihidro-pteridinonas, metodo para la produccion y uso del mismo en la forma de farmacos. |
| US8084582B2 (en) | 2003-03-03 | 2011-12-27 | Xencor, Inc. | Optimized anti-CD20 monoclonal antibodies having Fc variants |
| GB0305152D0 (en) | 2003-03-06 | 2003-04-09 | Novartis Ag | Organic compounds |
| GB2400101A (en) | 2003-03-28 | 2004-10-06 | Biofocus Discovery Ltd | Compounds capable of binding to the active site of protein kinases |
| AR044519A1 (es) | 2003-05-02 | 2005-09-14 | Novartis Ag | Derivados de piridin-tiazol amina y de pirimidin-tiazol amina |
| AR044388A1 (es) | 2003-05-20 | 2005-09-07 | Applied Molecular Evolution | Moleculas de union a cd20 |
| KR100883703B1 (ko) | 2003-05-30 | 2009-02-12 | 파마셋 인코포레이티드 | 변형 불소화 뉴클레오시드 유사체 |
| CN1842526A (zh) | 2003-06-26 | 2006-10-04 | 麦克公司 | 苯并二氮杂䓬cgrp受体拮抗剂 |
| DE602004013160T2 (de) | 2003-07-17 | 2009-07-02 | University Of Dundee, Dundee | Verfahren zur anwendung eines an lkb1/strad/mo25-komplexes |
| US8147832B2 (en) | 2003-08-14 | 2012-04-03 | Merck Patent Gmbh | CD20-binding polypeptide compositions and methods |
| GB0320197D0 (en) | 2003-08-28 | 2003-10-01 | Novartis Ag | Organic compounds |
| US20080194019A1 (en) | 2003-09-09 | 2008-08-14 | Beth Israel Deaconess Medical Center, Inc. | Tumor Suppressor Lkb1 Kinase Directly Activates Amp-Activated Kinase |
| CN101123968A (zh) | 2004-06-04 | 2008-02-13 | 艾科斯有限公司 | 肥大细胞病的治疗方法 |
| DE102004029784A1 (de) | 2004-06-21 | 2006-01-05 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 2-Benzylaminodihydropteridinone, Verfahren zur deren Herstellung und deren Verwendung als Arzneimittel |
| WO2006001266A1 (ja) | 2004-06-23 | 2006-01-05 | Banyu Pharmaceutical Co., Ltd. | 2-アリールプリン誘導体の製造方法 |
| US20060058311A1 (en) | 2004-08-14 | 2006-03-16 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation |
| GB0420719D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| CN101065016A (zh) | 2004-09-24 | 2007-10-31 | 詹森药业有限公司 | 蛋白激酶的抑制剂咪唑并[4,5-b]吡嗪酮 |
| GB0423653D0 (en) | 2004-10-25 | 2004-11-24 | Piramed Ltd | Pharmaceutical compounds |
| WO2006045828A1 (en) | 2004-10-29 | 2006-05-04 | Tibotec Pharmaceuticals Ltd. | Hiv inhibiting bicyclic pyrimidine derivatives |
| WO2006050076A1 (en) | 2004-10-29 | 2006-05-11 | Janssen Pharmaceutica, N.V. | Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders |
| SE0403006D0 (sv) | 2004-12-09 | 2004-12-09 | Biovitrum Ab | New compounds |
| US7767687B2 (en) | 2004-12-13 | 2010-08-03 | Biogen Idec Ma Inc. | Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as RAF kinase inhibitors |
| WO2006087530A1 (en) | 2005-02-16 | 2006-08-24 | Astrazeneca Ab | Chemical compounds |
| WO2006091737A1 (en) | 2005-02-24 | 2006-08-31 | Kemia, Inc. | Modulators of gsk-3 activity |
| KR20070108916A (ko) | 2005-02-25 | 2007-11-13 | 쿠도스 파마슈티칼스 리미티드 | Mtor 억제제로서 작용하는 하이드라지노메틸,하이드라조노메틸 및 5-원 복소환 화합물 및 이의항암제로서의 용도 |
| WO2006090169A1 (en) | 2005-02-25 | 2006-08-31 | Kudos Pharmaceuticals Limited | 2,4-diamino-pyridopyrimidine derivatives and their use as mtor inhibitors |
| EP1865058B1 (en) | 2005-03-31 | 2011-01-12 | Biomedics Inc. | Anti-cd-20 monoclonal antibody |
| AU2006232105A1 (en) | 2005-04-05 | 2006-10-12 | Pharmacopeia, Inc. | Purine and imidazopyridine derivatives for immunosuppression |
| CA2610234A1 (en) | 2005-06-02 | 2006-12-07 | Astrazeneca Ab | Antibodies directed to cd20 and uses thereof |
| CN102746298A (zh) | 2005-10-07 | 2012-10-24 | 埃克塞里艾克西斯公司 | PI3Kα的吡啶并嘧啶酮抑制剂 |
| RS53627B1 (sr) | 2005-10-07 | 2015-04-30 | Exelixis Inc. | Derivati n-(3-amino-hinoksalin-2-il)-sulfonamida i njihova upotreba kao inhibitora fosfatidilinozitol3-kinaze |
| NZ594628A (en) | 2005-10-07 | 2013-04-26 | Exelixis Inc | PYRIDOPYRIMIDINONE INHIBITORS OF PI3Ka |
| WO2007047754A2 (en) | 2005-10-18 | 2007-04-26 | George Mason Intellectual Properties, Inc. | Mtor pathway theranostic |
| EP2385053B1 (en) | 2005-11-17 | 2013-10-02 | OSI Pharmaceuticals, Inc. | Intermediates for the preparation of fused bicyclic mTOR inhibitors |
| WO2007060404A1 (en) | 2005-11-22 | 2007-05-31 | Kudos Pharmaceuticals Limited | PYRIDO-,PYRAZO- AND PYRIMIDO-PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS |
| GB0525080D0 (en) | 2005-12-09 | 2006-01-18 | Astrazeneca Ab | Pyrimidine derivatives |
| GB0525083D0 (en) | 2005-12-09 | 2006-01-18 | Astrazeneca Ab | Pyrimidine derivatives |
| KR20080083188A (ko) | 2006-01-11 | 2008-09-16 | 아스트라제네카 아베 | 모르폴리노 피리미딘 유도체 및 요법에서의 그 유도체의용도 |
| US20090281075A1 (en) | 2006-02-17 | 2009-11-12 | Pharmacopeia, Inc. | Isomeric purinones and 1h-imidazopyridinones as pkc-theta inhibitors |
| FI3719018T3 (fi) | 2006-04-25 | 2025-10-07 | Astex Therapeutics Ltd | Puriini- ja deatsapuriinijohdannaisia farmaseuttisina yhdisteinä |
| BRPI0710874A2 (pt) | 2006-04-26 | 2012-02-14 | Hoffmann La Roche | compostos de tienopirimidina, processos de produção dos referidos compostos, composições farmacêuticas contendo os mesmos, kit, produto, e usos dos compostos |
| CN101484452A (zh) | 2006-05-03 | 2009-07-15 | 阿斯利康(瑞典)有限公司 | 噻唑衍生物及其作为抗肿瘤药物的用途 |
| US20090118336A1 (en) | 2006-05-03 | 2009-05-07 | Laurent David | Pyrazole derivatives and their use as pi3k inhibitors |
| US20090306126A1 (en) | 2006-05-22 | 2009-12-10 | Astrazeneca Ab | Indole Derivatives |
| KR101410453B1 (ko) | 2006-08-02 | 2014-06-27 | 싸이토키네틱스, 인코포레이티드 | 소정의 화학 물질, 조성물 및 방법 |
| HUE033894T2 (en) | 2006-08-23 | 2018-01-29 | Kudos Pharm Ltd | 2-Methylmorpholine pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as MTOR inhibitors |
| WO2008079460A2 (en) | 2006-09-05 | 2008-07-03 | Emory University | Tyrosine kinase inhibitors for prevention or treatment of infection |
| US20100144738A1 (en) | 2006-09-05 | 2010-06-10 | William Bornmann | Inhibitors of c-met and uses thereof |
| WO2008032036A1 (en) | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | 6-benzimidaz0lyl-2-m0rph0lin0-4- (azetidine, pyrrolidine, piperidine or azepine) pyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders |
| WO2008032060A1 (en) | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | 4-benzimidaz0lyl-6-m0rph0lin0-2-piperazinylpyrimidine derivatives as p13k and mtor inhibitors for the treatment of proliferative disorders |
| WO2008032027A1 (en) | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | Pyrimidine derivatives |
| WO2008032089A1 (en) | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | 4-benzimidaz0lyl-2-m0rph0lin0-6-piperidin-4-ylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders |
| WO2008032028A1 (en) | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | 2 -benzimidazolyl- 6 -morpholino-4- (azetidine, pyrrolidine, piperidine or azepine) pyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders |
| WO2008032077A1 (en) | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | Pyrimidine derivatives |
| WO2008032091A1 (en) | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | 4-benzimidaz0lyl-6-m0rph0lin0-2-piperidin-4-ylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders |
| WO2008032072A1 (en) | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | 2-benzimidaz0lyl-6-m0rph0lin0-4-piperidin-4-ylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders |
| JP2010503649A (ja) | 2006-09-14 | 2010-02-04 | アストラゼネカ アクチボラグ | ピリミジン誘導体 |
| WO2008032033A1 (en) | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | 4-benzimidazolyl-2-morpholino-6-piperazinylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders |
| PT2066656E (pt) | 2006-09-26 | 2012-06-28 | Celgene Corp | Derivados de quinazolina substituídos em 5 como agentes antitumorais |
| US7902187B2 (en) | 2006-10-04 | 2011-03-08 | Wyeth Llc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| TW200831104A (en) | 2006-10-04 | 2008-08-01 | Pharmacopeia Inc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| MX2009004077A (es) | 2006-10-19 | 2009-05-05 | Signal Pharm Llc | Compuestos de heteroarilo, composiciones de los mismos, y su uso como inhibidores de proteina cinasas. |
| ZA200902384B (en) | 2006-10-19 | 2010-07-28 | Signal Pharm Llc | Heteroaryl compounds, compositions thereof, and use thereof as protein kinase inhibitors |
| UA98473C2 (ru) | 2006-11-20 | 2012-05-25 | Новартіс Аг | СОЛИ И КРИСТАЛЛИЧЕСКИЕ ФОРМЫ 2-МЕТИЛ-2-[4-(3-МЕТИЛ-2-ОКСО-8-ХИНОЛИН-3-ИЛ-2,3-ДИГИДРОИМИДАЗО[4,5-с]ХИНОЛИН-1-ИЛ)ФЕНИЛ]ПРОПИОНИТРИЛА |
| US20080234262A1 (en) | 2007-03-21 | 2008-09-25 | Wyeth | Pyrazolopyrimidine analogs and their use as mtor kinase and pi3 kinase inhibitors |
| UA99284C2 (ru) | 2007-05-11 | 2012-08-10 | Елі Ліллі Енд Компані | ИНГИБИТОРЫ р70 S6-КИНАЗЫ |
| EA201000092A1 (ru) | 2007-07-09 | 2010-06-30 | Астразенека Аб | Тризамещенные пиримидиновые производные для лечения пролиферативных заболеваний |
| CA2692720A1 (en) | 2007-07-09 | 2009-01-15 | Astrazeneca Ab | Morpholino pyrimidine derivatives used in diseases linked to mtor kinase and/or pi3k |
| AU2008273892A1 (en) | 2007-07-09 | 2009-01-15 | Astrazeneca Ab | Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases |
| NZ583019A (en) | 2007-07-31 | 2011-05-27 | Regeneron Pharma | Human antibodies to human cd20 and method of using thereof |
| EP2197918B1 (en) | 2007-09-05 | 2013-12-18 | F. Hoffmann-La Roche AG | Combination therapy with type i and type ii anti-cd20 antibodies |
| CA2704710C (en) | 2007-09-26 | 2016-02-02 | Celgene Corporation | 6-, 7-, or 8-substituted quinazolinone derivatives and compositions comprising the same |
| JP2011500702A (ja) | 2007-10-16 | 2011-01-06 | ワイス・エルエルシー | チエノピリミジンおよびピラゾロピリミジン化合物ならびにmTORキナーゼおよびPI3キナーゼ阻害剤としてのその使用 |
| AU2008345225A1 (en) | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| EA201001017A1 (ru) | 2008-01-15 | 2011-02-28 | ВАЙЕТ ЭлЭлСи | 3h-[1,2,3]триазоло[4,5-d]пиримидиновые соединения, их применение в качестве ингибиторов киназы mtor и киназы pi3 и их синтезы |
| US20110091574A1 (en) | 2008-02-15 | 2011-04-21 | Catholic Healthcare West | Treatment of adenocarcinoma expressing lkb1 with mtor inhibitor in combination with cox2 inhibitor |
| NZ624345A (en) | 2008-06-27 | 2016-07-29 | Celgene Avilomics Res Inc | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
| CN102271683B (zh) * | 2008-11-13 | 2014-07-09 | 吉里德卡利斯托加公司 | 恶性血液病的治疗 |
| US8877772B2 (en) | 2008-11-25 | 2014-11-04 | University Of Rochester | Substituted pyrrolo[2,3-B]pyridines as MLK inhibitors |
| WO2010137547A1 (ja) | 2009-05-25 | 2010-12-02 | 国立大学法人東京工業大学 | 中枢神経細胞の増殖及び分化に係る中核因子を含む医薬組成物 |
| CA2772253C (en) | 2009-09-14 | 2018-02-27 | Gilead Sciences, Inc. | Modulators of toll-like receptors |
| JP2013508456A (ja) | 2009-10-26 | 2013-03-07 | シグナル ファーマシューティカルズ, エルエルシー | ヘテロアリール化合物の合成方法および精製方法 |
| JP2013515734A (ja) | 2009-12-23 | 2013-05-09 | エラン ファーマシューティカルズ,インコーポレイテッド | ポロ様キナーゼの阻害薬としてのプテリジノン |
| EP2992878A1 (en) | 2010-02-03 | 2016-03-09 | Signal Pharmaceuticals, LLC | Identification of lkb1 mutation as a predictive biomarker for sensitivity to tor kinase inhibitors |
| CA2792872A1 (en) | 2010-03-12 | 2011-09-15 | Celgene Corporation | Methods for the treatment of non-hodgkin's lymphomas using lenalidomide, and gene and protein biomarkers as a predictor |
| US20110318336A1 (en) | 2010-03-29 | 2011-12-29 | George Mason Intellectual Properties, Inc. | Identification and Treatment of Aggressive Lung Cancer Tumors |
| US20120028972A1 (en) * | 2010-07-30 | 2012-02-02 | Lilly Wong | Biomarker assays for detecting or measuring inhibition of tor kinase activity |
| CA3037184C (en) * | 2011-03-11 | 2021-04-06 | Celgene Corporation | Solid forms of 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)-piperidine-2,6-dione, and their pharmaceutical compositions and uses |
| AU2012290056B2 (en) | 2011-08-03 | 2015-03-19 | Signal Pharmaceuticals, Llc | Identification of gene expression profile as a predictive biomarker for LKB1 status |
| US9493466B2 (en) * | 2011-10-19 | 2016-11-15 | Signal Pharmaceuticals, Llc | Treatment of cancer with TOR kinase inhibitors |
| ES2694413T3 (es) * | 2011-12-02 | 2018-12-20 | Signal Pharmaceuticals, Llc | Composiciones farmacéuticas de 7-(6-(2-hidroxipropan-2-il)piridin-3-il)-1-((trans)-4-metoxiciclohexil)-3,4-dihidropirazino [2,3-b]pirazin-2(1H)-ona, una forma sólida de la misma y métodos para su uso |
| CA2864905A1 (en) | 2012-02-24 | 2013-08-29 | Signal Pharmaceuticals, Llc | Methods for treating non- small cell lung cancer using tor kinase inhibitor combination therapy |
| MX360880B (es) | 2012-03-15 | 2018-11-21 | Signal Pharm Llc | Compuesto 1-etil-7-(2-metil-6-(1h-1,2,4-triazol-3-il)piridin-3il)- 3,4-dihidropirazino [2,3-b]pirazin-2(1h)-ona para usarse en el tratamiento de cancer de mama triple negativo. |
| MY182650A (en) | 2012-03-15 | 2021-01-27 | Signal Pharm Llc | Treatment of cancer with tor kinase inhibitors |
| UA114194C2 (uk) | 2012-03-15 | 2017-05-10 | Сігнал Фармасьютікалз, Елелсі | Лікування раку інгібітором тоr кінази |
| KR102122617B1 (ko) | 2012-03-15 | 2020-06-12 | 시그날 파마소티칼 엘엘씨 | Tor 키나제 억제자를 사용하는 암의 치료 |
| AU2013203714B2 (en) | 2012-10-18 | 2015-12-03 | Signal Pharmaceuticals, Llc | Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity |
| MX364101B (es) | 2013-04-17 | 2019-04-12 | Signal Pharm Llc | Terapia de combinación que comprende un compuesto de dihidropirazino-pirazina y un antagonista de receptor de andrógenos para tratar cáncer de próstata. |
| CA2909579A1 (en) * | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Combination therapy comprising a tor kinase inhibitor and n-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide for treating cancer |
| WO2014172432A1 (en) | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Combination therapy comprising a tor kinase inhibitor and a cytidine analog for treating cancer |
| TW201526897A (zh) * | 2013-04-17 | 2015-07-16 | Signal Pharm Llc | 使用tor激酶抑制劑組合療法以治療癌症之方法 |
| HK1221150A1 (zh) | 2013-04-17 | 2017-05-26 | 西格诺药品有限公司 | 用二氢吡嗪并-吡嗪类对癌症的治疗 |
| WO2014172424A1 (en) | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Treatment of cancer with dihydropyrazino-pyrazines |
| SG11201508527VA (en) | 2013-04-17 | 2015-11-27 | Signal Pharm Llc | Pharmaceutical formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl) pyridin-3-yl) -3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one |
| EA030808B1 (ru) | 2013-04-17 | 2018-09-28 | СИГНАЛ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | ПРИМЕНЕНИЕ 1-ЭТИЛ-7-(2-МЕТИЛ-6-(1Н-1,2,4-ТРИАЗОЛ-3-ИЛ)ПИРИДИН-3-ИЛ)-3,4-ДИГИДРОПИРАЗИНО[2,3-b]ПИРАЗИН-2(1Н)-ОНА В ЛЕЧЕНИИ МУЛЬТИФОРМНОЙ ГЛИОБЛАСТОМЫ |
-
2014
- 2014-04-16 HK HK16109443.6A patent/HK1221174A1/zh unknown
- 2014-04-16 CA CA2909625A patent/CA2909625C/en active Active
- 2014-04-16 JP JP2016509059A patent/JP6382949B2/ja active Active
- 2014-04-16 TW TW103113959A patent/TWI654979B/zh active
- 2014-04-16 WO PCT/US2014/034321 patent/WO2014172436A1/en not_active Ceased
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-
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- 2015-10-15 ZA ZA2015/07730A patent/ZA201507730B/en unknown
- 2015-10-15 IL IL242100A patent/IL242100B/en active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102245611A (zh) * | 2008-10-27 | 2011-11-16 | 西格诺药品有限公司 | 用于与 mTOR/PI3K/AKT/途径相关的肿瘤适应症和疾病的 mTOR激酶抑制剂 |
| US20120230983A1 (en) * | 2011-03-11 | 2012-09-13 | Muller George W | Methods of treating cancer using 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)-piperidine-2,6-dione |
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| AU2014253978A1 (en) | 2015-11-12 |
| CN105339009B (zh) | 2018-08-28 |
| MX368286B (es) | 2019-09-27 |
| JP2016516821A (ja) | 2016-06-09 |
| MX2015014591A (es) | 2016-03-03 |
| HK1221174A1 (zh) | 2017-05-26 |
| BR112015026297A2 (pt) | 2017-07-25 |
| CN105339009A (zh) | 2016-02-17 |
| JP6382949B2 (ja) | 2018-08-29 |
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