EA030808B1 - 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 - Google Patents
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 Download PDFInfo
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- EA030808B1 EA030808B1 EA201591987A EA201591987A EA030808B1 EA 030808 B1 EA030808 B1 EA 030808B1 EA 201591987 A EA201591987 A EA 201591987A EA 201591987 A EA201591987 A EA 201591987A EA 030808 B1 EA030808 B1 EA 030808B1
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Classifications
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- 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
- A61K49/00—Preparations for testing in vivo
- A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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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
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
Landscapes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Pathology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Diabetes (AREA)
- Toxicology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Physics & Mathematics (AREA)
- Oncology (AREA)
- Biophysics (AREA)
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- Microbiology (AREA)
- Molecular Biology (AREA)
- Hospice & Palliative Care (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Neurology (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361813071P | 2013-04-17 | 2013-04-17 | |
| PCT/US2014/034304 WO2014172425A1 (en) | 2013-04-17 | 2014-04-16 | Treatment of cancer with dihydropyrazino-pyrazines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201591987A1 EA201591987A1 (ru) | 2016-03-31 |
| EA030808B1 true EA030808B1 (ru) | 2018-09-28 |
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| Application Number | Title | Priority Date | Filing Date |
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| EA201591987A EA030808B1 (ru) | 2013-04-17 | 2014-04-16 | 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 |
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| EP (2) | EP4218763A1 (OSRAM) |
| JP (1) | JP6382945B2 (OSRAM) |
| KR (1) | KR102271344B1 (OSRAM) |
| CN (2) | CN105473142A (OSRAM) |
| AU (1) | AU2014254052B2 (OSRAM) |
| BR (1) | BR112015026238A8 (OSRAM) |
| CA (1) | CA2908353C (OSRAM) |
| EA (1) | EA030808B1 (OSRAM) |
| ES (1) | ES2944478T3 (OSRAM) |
| IL (1) | IL241950B (OSRAM) |
| MX (2) | MX377267B (OSRAM) |
| NI (1) | NI201500150A (OSRAM) |
| NZ (1) | NZ629332A (OSRAM) |
| PH (3) | PH12021552945B1 (OSRAM) |
| SA (1) | SA515370012B1 (OSRAM) |
| SG (2) | SG11201508223YA (OSRAM) |
| TW (2) | TWI631950B (OSRAM) |
| UA (1) | UA119538C2 (OSRAM) |
| WO (1) | WO2014172425A1 (OSRAM) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2744198T3 (es) | 2013-04-17 | 2020-02-24 | Signal Pharm Llc | Formulaciones farmacéuticas, procesos, formas sólidas y procedimientos de uso relacionados con 1-etil-7-(2-metil-6-(1H-1,2,4-triazol-3-il)piridin-3-il)-3, 4 dihidropirazino[2,3-b]pirazin-2(1H)-ona |
| KR102240356B1 (ko) | 2013-04-17 | 2021-04-14 | 시그날 파마소티칼 엘엘씨 | Ｔｏｒ 키나제 억제제와 5-치환된 퀴나졸리논 화합물을 포함하는 암 치료용 조합 요법 |
| CN105377260B (zh) | 2013-04-17 | 2020-06-12 | 西格诺药品有限公司 | 二氢吡嗪并-吡嗪类化合物在制备治疗癌症的药物中的应用 |
| JP6382947B2 (ja) | 2013-04-17 | 2018-08-29 | シグナル ファーマシューティカルズ，エルエルシー | 前立腺癌を治療するためのジヒドロピラジノ−ピラジン化合物及びアンドロゲン受容体アンタゴニストを含む組合せ療法 |
| WO2014193912A1 (en) | 2013-05-29 | 2014-12-04 | Signal Pharmaceuticals, Llc | Pharmaceutical compositions of 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 |
| 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 |
| WO2015160868A1 (en) | 2014-04-16 | 2015-10-22 | Signal Pharmaceuticals, Llc | Methods for treating cancer using tor kinase inhibitor combination therapy |
| 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 |
| WO2017031116A1 (en) * | 2015-08-18 | 2017-02-23 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Small molecule inhibitors of ku70/80 and uses thereof |
| WO2018004258A1 (ko) * | 2016-06-28 | 2018-01-04 | 한미약품 주식회사 | 신규한 헤테로시클릭 유도체 화합물 및 이의 용도 |
| KR20180002053A (ko) * | 2016-06-28 | 2018-01-05 | 한미약품 주식회사 | 신규한 헤테로시클릭 유도체 화합물 및 이의 용도 |
| EA202090103A1 (ru) | 2017-06-22 | 2020-04-24 | Селджин Корпорейшн | Лечение гепатоцеллюлярной карциномы, которая характеризуется вирусной инфекцией гепатита b |
| WO2022266468A1 (en) * | 2021-06-18 | 2022-12-22 | Yale University | Anti-cancer compounds and methods of use |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008051493A2 (en) * | 2006-10-19 | 2008-05-02 | Signal Pharmaceuticals, Llc | Heteroaryl compounds, compositions thereof, and their use as protein kinase inhibitors |
| WO2010062571A1 (en) * | 2008-10-27 | 2010-06-03 | Signal Pharmaceuticals, Llc | Mtor kinase inhibitors for oncology indications and diseases associated with the mtor/p13k/akt pathway |
| WO2011053518A1 (en) * | 2009-10-26 | 2011-05-05 | Signal Pharmaceuticals, Llc | Methods of synthesis and purification of heteroaryl compounds |
| WO2012016113A1 (en) * | 2010-07-30 | 2012-02-02 | Signal Pharmaceuticals, Llc | Biomarker assays for detecting or measuring inhibition of tor kinase activity |
| WO2013059396A2 (en) * | 2011-10-19 | 2013-04-25 | Signal Pharmaceuticals, Llc | Treatment of cancer with tor kinase inhibitors |
| WO2013082344A1 (en) * | 2011-12-02 | 2013-06-06 | Signal Pharmaceuticals, Llc | Pharmaceutical compositions of 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 |
Family Cites Families (122)
| 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 |
| 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 |
| 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 |
| 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 (OSRAM) | 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 |
| NZ503432A (en) | 1997-09-26 | 2002-11-26 | Zentaris Gmbh | Azabenzimidazole-based compounds for modulating serine/threonine protein kinase function |
| EP1036844A4 (en) | 1997-11-27 | 2002-12-04 | Chugai Pharmaceutical Co Ltd | Test methods, test reagent and remedies for diseases caused by changes in the 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 |
| 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 |
| WO2000072670A1 (en) | 1999-05-31 | 2000-12-07 | Chugai Research Institute For Molecular Medicine, Inc. | Lkb1 gene knockout animals |
| 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 |
| ATE310004T1 (de) | 2000-12-12 | 2005-12-15 | Neurogen Corp | Spiro(isobenzofuran-1,4'-piperidin)-3-one und 3h- spiroisobenzofuran-1,4'-piperidine |
| WO2002076954A1 (en) | 2001-03-23 | 2002-10-03 | Smithkline Beecham Corporation | Compounds useful as kinase inhibitors for the treatment of hyperproliferative diseases |
| WO2003020722A1 (de) | 2001-09-04 | 2003-03-13 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue dihydropteridinone, verfahren zu deren herstellung und deren verwendung als arzneimittel |
| EP1438048A1 (en) | 2001-10-18 | 2004-07-21 | Boehringer Ingelheim Pharmaceuticals Inc. | 1,4-disubstituted benzo-fused urea compounds as cytokine inhibitors |
| 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 |
| MXPA04010983A (es) | 2002-05-06 | 2005-02-14 | Genelabs Tech Inc | Derivados de nucleosidos para tratar infecciones por el virus de la hepatitis c. |
| US20040204420A1 (en) | 2002-08-05 | 2004-10-14 | Rana Tariq M. | Compounds for modulating RNA interference |
| JP2006512313A (ja) | 2002-10-31 | 2006-04-13 | アムジェン インコーポレイテッド | 抗炎症剤 |
| MXPA05005477A (es) | 2002-11-21 | 2005-07-25 | Chiron Corp | Pirimidinas 2,4,6-trisustituidas como inhibidores de fosfotidilinositol (pi) 3-cinasa y su uso en el tratamiento del cancer. |
| WO2004065378A1 (en) | 2003-01-17 | 2004-08-05 | Warner-Lambert Company Llc | 2-aminopyridine substituted heterocycles as inhibitors of cellular proliferation |
| RS52386B (sr) | 2003-02-26 | 2013-02-28 | Boehringer Ingelheim Pharma Gmbh & Co.Kg. | Dihidropteridinoni, postupak za njihovo pripremanje i njihova primena kao leka |
| 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 |
| TW200519106A (en) | 2003-05-02 | 2005-06-16 | Novartis Ag | Organic compounds |
| ES2586668T5 (es) | 2003-05-30 | 2024-11-12 | Gilead Pharmasset Llc | Análogos de nucleósidos fluorados modificados |
| EP1641423B1 (en) | 2003-06-26 | 2010-03-17 | Merck Sharp & Dohme Corp. | Benzodiazepine cgrp receptor antagonists |
| WO2005010174A2 (en) | 2003-07-17 | 2005-02-03 | University Of Dundee | Methods for use of an lkb1/strad7mo25 complex |
| 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 |
| CA2569406A1 (en) | 2004-06-04 | 2005-12-22 | Icos Corporation | Methods for treating mast cell disorders |
| 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 |
| EP1807430B1 (en) | 2004-10-29 | 2014-07-23 | Janssen R&D Ireland | 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 |
| NZ554831A (en) * | 2004-11-09 | 2009-10-30 | Schering Corp | Improved dosing regimen of temozolomide for treating cancer based on the patientÆs MGMT level |
| SE0403006D0 (sv) | 2004-12-09 | 2004-12-09 | Biovitrum Ab | New compounds |
| WO2006065703A1 (en) | 2004-12-13 | 2006-06-22 | Sunesis Pharmaceuticals, Inc. | Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as raf kinase inhibitors |
| US8129403B2 (en) | 2005-02-16 | 2012-03-06 | Astrazeneca Ab | Chemical compounds |
| WO2006091737A1 (en) | 2005-02-24 | 2006-08-31 | Kemia, Inc. | Modulators of gsk-3 activity |
| AU2006217742A1 (en) | 2005-02-25 | 2006-08-31 | Kudos Pharmaceuticals Limited | Hydrazinomethyl, HYDR zonomethyl and 5-membered heterocylic compounds which act as MTOR inhibitors and their use as anti cancer agents |
| JP2008531538A (ja) | 2005-02-25 | 2008-08-14 | クドス ファーマシューティカルズ リミテッド | ２，４−ジアミノ−ピリドピリミジン誘導体とｍＴＯＲ阻害剤としてのその使用 |
| RU2007140903A (ru) | 2005-04-05 | 2009-05-20 | Фармакопия, Инк. (Us) | Производные пурина и имидазопиридина для иммуносупрессии |
| NZ608667A (en) | 2005-10-07 | 2014-08-29 | Exelixis Inc | N-(3-amino-quinoxalin-2-yl)-sulfonamide derivatives and their use as phosphatidylinositol 3-kinase inhibitors |
| HRP20130902T1 (hr) | 2005-10-07 | 2013-11-08 | Exelixis Inc. | PIRIDOPIRIMIDINONSKI INHIBITORI PI3Kalfa |
| US8247408B2 (en) | 2005-10-07 | 2012-08-21 | Exelixis, Inc. | Pyridopyrimidinone inhibitors of PI3Kα for the treatment of cancer |
| WO2007047754A2 (en) | 2005-10-18 | 2007-04-26 | George Mason Intellectual Properties, Inc. | Mtor pathway theranostic |
| CN102936250B (zh) | 2005-11-17 | 2014-07-09 | Osi医药有限责任公司 | 稠合双环mTOR抑制剂 |
| HRP20120963T1 (hr) | 2005-11-22 | 2012-12-31 | Kudos Pharmaceuticals Ltd | PIRIDO-, PIRAZO- I PIRIMIDOPIRIMIDINSKI DERIVATI KAO mTOR INHIBITORI |
| GB0525083D0 (en) | 2005-12-09 | 2006-01-18 | Astrazeneca Ab | Pyrimidine derivatives |
| GB0525080D0 (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 |
| WO2007125321A2 (en) | 2006-04-25 | 2007-11-08 | Astex Therapeutics Limited | Purine and deazapurine derivatives as pharmaceutical compounds |
| NZ572812A (en) | 2006-04-26 | 2010-09-30 | Hoffmann La Roche | THIENO [3, 2-D] PYRIMIDINE Indazole DERIVATIVE USEFUL AS PI3K INHIBITOR |
| 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 |
| JP2009535388A (ja) | 2006-05-03 | 2009-10-01 | アストラゼネカ アクチボラグ | ピラゾール誘導体、及びそのｐｉ３ｋ阻害薬としての使用 |
| WO2007135398A1 (en) | 2006-05-22 | 2007-11-29 | Astrazeneca Ab | Indole derivatives |
| PL2583970T3 (pl) | 2006-08-02 | 2016-05-31 | Cytokinetics Inc | Określone cząstki chemiczne, kompozycje i sposoby zawierające imidazopirymidyny |
| BRPI0715888B1 (pt) | 2006-08-23 | 2021-11-03 | Kudos Pharmaceuticals Limited | Composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, e, uso de um composto |
| EP2063882A4 (en) | 2006-09-05 | 2010-03-03 | Univ Emory | TYROSINKINASE INHIBITOR FOR PREVENTING OR TREATING INFECTIONS |
| WO2008030744A2 (en) | 2006-09-05 | 2008-03-13 | Board Of Regents, The University Of Texas System | Inhibitors of c-met and uses thereof |
| WO2008032064A1 (en) | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | Pyrimidine derivatives |
| 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 |
| 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 |
| WO2008032027A1 (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 |
| 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 |
| CN101563339A (zh) | 2006-09-14 | 2009-10-21 | 阿斯利康(瑞典)有限公司 | 作为 p i 3 k和 m t o r抑制剂用于治疗增殖性疾病的 2 -苯并咪唑基 - 6 -吗啉代 - 4 - (氮杂环丁烷、吡咯烷、哌啶或氮杂)嘧啶衍生物 |
| EP2064203A1 (en) | 2006-09-14 | 2009-06-03 | AstraZeneca AB | 2-benzimidaz0lyl-6-m0rph0lin0-4-piperidin-4-ylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders |
| WO2008032077A1 (en) | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | Pyrimidine derivatives |
| 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 |
| US7902187B2 (en) | 2006-10-04 | 2011-03-08 | Wyeth Llc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| WO2008043031A1 (en) | 2006-10-04 | 2008-04-10 | Pharmacopeia, Inc. | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| ATE549336T1 (de) | 2006-10-19 | 2012-03-15 | Signal Pharm Llc | Heteroarylverbindungen,zusammensetzungen daraus und ihre verwendung als proteinkinasehemmer |
| US8436177B2 (en) | 2006-11-20 | 2013-05-07 | Novartis Ag | Salts and crystall forms of 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile |
| 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 |
| AU2008273892A1 (en) | 2007-07-09 | 2009-01-15 | Astrazeneca Ab | Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases |
| BRPI0814818A2 (pt) | 2007-07-09 | 2019-09-10 | Astrazeneca Ab | composto, uso de um composto, métodos para produzir um efeito anti-proliferativo e um efeito inibitório de mtor quinase em uma animal de sangue quente, método para tratar doenças, e, composição farmacêutica |
| EP2176238B1 (en) | 2007-07-09 | 2012-04-18 | AstraZeneca AB | Morpholino pyrimidine derivatives used in diseases linked to mtor kinase and/or pi3k |
| AU2008312631A1 (en) | 2007-10-16 | 2009-04-23 | Wyeth Llc | Thienopyrimidine and pyrazolopyrimidine compounds and their use as mTOR kinase and PI3 kinase inhibitors |
| CA2709784A1 (en) | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| AU2009205501A1 (en) | 2008-01-15 | 2009-07-23 | Wyeth Llc | 3H-[1,2,3]triazolo[4,5-d]pyrimidine compounds, their use as mTOR kinase and PI3 kinase inhibitors, and their syntheses |
| WO2009102986A1 (en) | 2008-02-15 | 2009-08-20 | Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center) | Treatment of adenocarcinoma expressing lkb1 with mtor inhibitor in combination with cox1 inhibitor |
| WO2010006072A2 (en) | 2008-07-08 | 2010-01-14 | The Regents Of The University Of California | Mtor modulators and uses thereof |
| EP3037421A3 (en) | 2008-11-25 | 2016-11-30 | University Of Rochester | Mlk inhibitors and methods of use |
| JP5763077B2 (ja) | 2009-09-14 | 2015-08-12 | ギリアード サイエンシーズ， インコーポレイテッド | トール様受容体のモジュレーター |
| US8541418B2 (en) | 2009-12-23 | 2013-09-24 | Elan Pharmaceutical, Inc. | Inhibitors of polo-like kinase |
| SG183155A1 (en) | 2010-02-03 | 2012-09-27 | Signal Pharm Llc | Identification of lkb1 mutation as a predictive biomarker for sensitivity to tor kinase inhibitors |
| US20110318336A1 (en) | 2010-03-29 | 2011-12-29 | George Mason Intellectual Properties, Inc. | Identification and Treatment of Aggressive Lung Cancer Tumors |
| CN105039520A (zh) | 2011-08-03 | 2015-11-11 | 西格诺药品有限公司 | 作为lkb1状态的预测性生物标志物的基因表达谱的鉴定 |
| TWI615143B (zh) | 2012-02-24 | 2018-02-21 | 標誌製藥公司 | 使用ｔｏｒ激酶抑制劑組合療法以治療癌症之方法 |
| SG11201405724RA (en) | 2012-03-15 | 2014-10-30 | Signal Pharm Llc | Treatment of cancer with tor kinase inhibitors |
| EA028062B1 (ru) | 2012-03-15 | 2017-10-31 | СИГНАЛ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | Лечение рака ингибиторами tor киназы |
| NZ628416A (en) | 2012-03-15 | 2016-04-29 | Signal Pharm Llc | Treatment of cancer with tor kinase inhibitors |
| CA2867349A1 (en) | 2012-03-15 | 2013-09-19 | Signal Pharmaceuticals, Llc | Treatment of cancer with tor kinase inhibitors |
| 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 |
| CN105392499B (zh) | 2013-04-17 | 2018-07-24 | 西格诺药品有限公司 | 用于治疗癌症的包含tor激酶抑制剂和胞苷类似物的组合疗法 |
| KR102240356B1 (ko) | 2013-04-17 | 2021-04-14 | 시그날 파마소티칼 엘엘씨 | Ｔｏｒ 키나제 억제제와 5-치환된 퀴나졸리논 화합물을 포함하는 암 치료용 조합 요법 |
| 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 |
| WO2014172424A1 (en) | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Treatment of cancer with dihydropyrazino-pyrazines |
| BR112015026021A2 (pt) | 2013-04-17 | 2017-07-25 | Signal Pharm Llc | terapia de combinação compreendendo um inibidor de tor quinase e n-(3-(5-flúor-2-(4-(2-met-oxietoxi)fenilamino)pirimidin-4-ilamino)fenil)acrilamida para o tratamento de câncer |
| CN105377260B (zh) | 2013-04-17 | 2020-06-12 | 西格诺药品有限公司 | 二氢吡嗪并-吡嗪类化合物在制备治疗癌症的药物中的应用 |
| JP6382947B2 (ja) | 2013-04-17 | 2018-08-29 | シグナル ファーマシューティカルズ，エルエルシー | 前立腺癌を治療するためのジヒドロピラジノ−ピラジン化合物及びアンドロゲン受容体アンタゴニストを含む組合せ療法 |
| ES2744198T3 (es) | 2013-04-17 | 2020-02-24 | Signal Pharm Llc | Formulaciones farmacéuticas, procesos, formas sólidas y procedimientos de uso relacionados con 1-etil-7-(2-metil-6-(1H-1,2,4-triazol-3-il)piridin-3-il)-3, 4 dihidropirazino[2,3-b]pirazin-2(1H)-ona |
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008051493A2 (en) * | 2006-10-19 | 2008-05-02 | Signal Pharmaceuticals, Llc | Heteroaryl compounds, compositions thereof, and their use as protein kinase inhibitors |
| WO2010062571A1 (en) * | 2008-10-27 | 2010-06-03 | Signal Pharmaceuticals, Llc | Mtor kinase inhibitors for oncology indications and diseases associated with the mtor/p13k/akt pathway |
| WO2011053518A1 (en) * | 2009-10-26 | 2011-05-05 | Signal Pharmaceuticals, Llc | Methods of synthesis and purification of heteroaryl compounds |
| WO2012016113A1 (en) * | 2010-07-30 | 2012-02-02 | Signal Pharmaceuticals, Llc | Biomarker assays for detecting or measuring inhibition of tor kinase activity |
| WO2013059396A2 (en) * | 2011-10-19 | 2013-04-25 | Signal Pharmaceuticals, Llc | Treatment of cancer with tor kinase inhibitors |
| WO2013082344A1 (en) * | 2011-12-02 | 2013-06-06 | Signal Pharmaceuticals, Llc | Pharmaceutical compositions of 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 |
Non-Patent Citations (2)
| Title |
|---|
| JHANWAR-UNIYAL: "Involvement of mTORC1 and mTORC2 in regulation of glioblastoma multiforme growth and motility", INTERNATIONAL JOURNAL OF ONCOLOGY, LYCHNIA, vol. 35, no. 4, 1 September 2009 (2009-09-01), XP055052309, ISSN: 10196439, DOI: 10.3892/ijo_00000386 * |
| P. WU, Y.-Z. HU: "PI3K/Akt/mTOR Pathway Inhibitors in Cancer: A Perspective on Clinical Progress", CURRENT MEDICINAL CHEMISTRY, BENTHAM SCIENCE PUBLISHERS, vol. 17, no. 35, 1 December 2010 (2010-12-01), pages 4326 - 4341, XP055052059, ISSN: 09298673, DOI: 10.2174/092986710793361234 * |
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