TW581815B - Methods of modulating serine/threonine protein kinase function with azabenzimidazole-based compounds - Google Patents
Methods of modulating serine/threonine protein kinase function with azabenzimidazole-based compounds Download PDFInfo
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- TW581815B TW581815B TW087115979A TW87115979A TW581815B TW 581815 B TW581815 B TW 581815B TW 087115979 A TW087115979 A TW 087115979A TW 87115979 A TW87115979 A TW 87115979A TW 581815 B TW581815 B TW 581815B
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- pyridine
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- protein kinase
- serine
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Classifications
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
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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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6014597P | 1997-09-26 | 1997-09-26 |
Publications (1)
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|---|---|
| TW581815B true TW581815B (en) | 2004-04-01 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW087115979A TW581815B (en) | 1997-09-26 | 1998-09-25 | Methods of modulating serine/threonine protein kinase function with azabenzimidazole-based compounds |
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|---|---|
| US (2) | US6093728A (enExample) |
| EP (1) | EP1017384B1 (enExample) |
| JP (1) | JP2001517699A (enExample) |
| KR (1) | KR100547929B1 (enExample) |
| CN (1) | CN1167420C (enExample) |
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Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060142236A1 (en) * | 1994-05-31 | 2006-06-29 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of raf gene expression |
| US6911462B2 (en) * | 1998-05-22 | 2005-06-28 | Avanir Pharmaceuticals | Benzimidazole compounds for regulating IgE |
| US6919366B2 (en) * | 1998-05-22 | 2005-07-19 | Avanir Pharmaceuticals | Benzimidazole derivatives as modulators of IgE |
| US6384049B1 (en) * | 2000-05-25 | 2002-05-07 | The Procter & Gamble Company | Cancer treatment |
| JP2004528304A (ja) * | 2001-03-12 | 2004-09-16 | アバニール・ファーマシューティカルズ | ＩｇＥを調節し、細胞増殖を阻害するためのベンゾイミダゾール化合物 |
| TW200304820A (en) * | 2002-03-25 | 2003-10-16 | Avanir Pharmaceuticals | Use of benzimidazole analogs in the treatment of cell proliferation |
| AU2003270426A1 (en) | 2002-09-12 | 2004-04-30 | Avanir Pharmaceuticals | PHENYL-INDOLE COMPOUNDS FOR MODULATING IgE AND INHIBITING CELLULAR PROLIFERATION |
| TWI276631B (en) * | 2002-09-12 | 2007-03-21 | Avanir Pharmaceuticals | Phenyl-aza-benzimidazole compounds for modulating IgE and inhibiting cellular proliferation |
| AU2004263190A1 (en) * | 2003-08-08 | 2005-02-17 | Avanir Pharmaceuticals | Selective pharmacologic inhibition of protein trafficking and related methods of treating human diseases |
| GB0423554D0 (en) | 2004-10-22 | 2004-11-24 | Cancer Rec Tech Ltd | Therapeutic compounds |
| EP1962892A4 (en) | 2005-11-22 | 2011-10-12 | Univ South Florida | INHIBITION OF CELL PROLIFERATION |
| WO2007125330A1 (en) | 2006-04-26 | 2007-11-08 | Cancer Research Technology Limited | Imidazo[4, 5-b]pyridin-2-one and oxazolo[4, 5-b]pyridin-2-one compounds and analogs thereof as cancer therapeutic compounds |
| 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. |
| US8748371B2 (en) * | 2007-02-28 | 2014-06-10 | Yeda Research And Development Co. Ltd. | Nuclear targeting sequences |
| PE20090370A1 (es) * | 2007-06-05 | 2009-04-30 | Takeda Pharmaceutical | Derivados de heterociclo fusionado como inhibidores de quinasa |
| 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 |
| JP5350247B2 (ja) | 2007-08-29 | 2013-11-27 | 武田薬品工業株式会社 | 複素環化合物およびその用途 |
| EA019974B1 (ru) | 2007-12-19 | 2014-07-30 | Кансер Рисерч Текнолоджи Лимитед | 8-ЗАМЕЩЕННЫЕ ПИРИДО[2,3-b]ПИРАЗИНЫ И ИХ ПРИМЕНЕНИЕ |
| GB0807609D0 (en) | 2008-04-25 | 2008-06-04 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| WO2010025448A2 (en) * | 2008-08-29 | 2010-03-04 | University Of South Florida | Inhibition of cell proliferation |
| US8110578B2 (en) | 2008-10-27 | 2012-02-07 | Signal Pharmaceuticals, Llc | Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway |
| JP5579619B2 (ja) | 2008-12-01 | 2014-08-27 | 武田薬品工業株式会社 | 複素環化合物およびその用途 |
| JO3101B1 (ar) | 2008-12-02 | 2017-09-20 | Takeda Pharmaceuticals Co | مشتقات بنزوثيازول كعوامل مضادة للسرطان |
| JP2012197231A (ja) * | 2009-08-06 | 2012-10-18 | Oncotherapy Science Ltd | Ｔｔｋ阻害作用を有するピリジンおよびピリミジン誘導体 |
| 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 |
| CN102906090B (zh) | 2010-02-01 | 2015-06-24 | 癌症研究技术有限公司 | 1-(5-叔丁基-2-苯基-2h-吡唑-3-基)-3-[2-氟-4-(1-甲基-2-氧代-2,3-二氢-1h-咪唑并[4,5-b]吡啶-7-基氧基)-苯基]-脲和相关化合物及它们在治疗中的应用 |
| 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 |
| 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 |
| HK1212207A1 (en) | 2013-01-16 | 2016-06-10 | 西格诺药品有限公司 | Substituted pyrrolopyrimidine compounds, compositions thereof, and methods of treatment therewith |
| WO2014145852A2 (en) | 2013-03-15 | 2014-09-18 | Knopp Biosciences Llc | Imidazo(4,5-b) pyridin-2-yl amides as kv7 channel activators |
| 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 |
| 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. |
| HK1221174A1 (zh) | 2013-04-17 | 2017-05-26 | 西格诺药品有限公司 | 用於治疗癌症的包括tor激酶抑制剂和5-取代喹唑啉酮化合物的组合疗法 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| WO2015040609A1 (en) | 2013-09-17 | 2015-03-26 | Yeda Research And Development Co. Ltd. | Erk-derived peptides and uses thereof |
| GB201320732D0 (en) | 2013-11-25 | 2014-01-08 | Cancer Rec Tech Ltd | Methods of chemical synthesis |
| GB201320729D0 (en) | 2013-11-25 | 2014-01-08 | Cancer Rec Tech Ltd | Therapeutic compounds and 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 |
| US9718824B2 (en) | 2014-04-16 | 2017-08-01 | Signal Pharmaceuticals, Llc | Solid forms comprising 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, and a coformer, compositions and methods of use thereof |
| 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 |
| 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 |
| KR20170024120A (ko) | 2014-07-14 | 2017-03-06 | 시그날 파마소티칼 엘엘씨 | 치환된 피롤로피리미딘 화합물을 사용한 암의 치료방법, 이의 조성물 |
| NZ629796A (en) | 2014-07-14 | 2015-12-24 | Signal Pharm Llc | Amorphous form of 4-((4-(cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7h-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-n-methylbenzamide, compositions thereof and methods of their use |
| WO2016040952A2 (en) | 2014-09-12 | 2016-03-17 | Knopp Biosciences Llc | BENZOIMIDAZOL-1,2-YL AMIDES AS Kv7 CHANNEL ACTIVATORS |
| MY198676A (en) | 2017-06-22 | 2023-09-15 | Celgene Corp | Treatment of hepatocellular carcinoma characterized by hepatitis b virus infection |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3590045A (en) * | 1969-09-25 | 1971-06-29 | Smith Kline French Lab | Certain substituted imidazo (4,5-b)pyridines |
| BE788065A (fr) | 1971-08-26 | 1973-02-26 | Degussa | Nouvelles aza-benzimidazoles et procede pour leur preparation |
| SE422799B (sv) | 1975-05-28 | 1982-03-29 | Merck & Co Inc | Analogiforfarande for framstellning av 1,3-dihydroimidazo (4,5-b)pyridin-2-oner |
| ES473201A1 (es) * | 1977-09-26 | 1979-03-16 | Degussa | Procedimiento para la preparacion de 7-azabencimidazoles |
| US5217999A (en) * | 1987-12-24 | 1993-06-08 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Styryl compounds which inhibit EGF receptor protein tyrosine kinase |
| ES2064101T3 (es) * | 1990-04-02 | 1995-01-16 | Pfizer | Compuestos de acido bencilfosfonico inhibidores de la quinasa de tirosina. |
| US5302606A (en) * | 1990-04-16 | 1994-04-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Styryl-substituted pyridyl compounds which inhibit EGF receptor tyrosine kinase |
| WO1992020642A1 (en) * | 1991-05-10 | 1992-11-26 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase |
| JPH06503095A (ja) * | 1991-05-29 | 1994-04-07 | ファイザー・インコーポレーテッド | 三環式ポリヒドロキシ系のチロシンキナーゼ阻害薬 |
| AU661533B2 (en) * | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| JPH08503450A (ja) * | 1992-08-06 | 1996-04-16 | ワーナー−ランバート・コンパニー | 蛋白チロシンキナーゼを阻害し、かつ抗腫瘍特性を有する２−チオインドール（セレノインドール）および関連ジスルフィド（セレニド） |
| US5330992A (en) * | 1992-10-23 | 1994-07-19 | Sterling Winthrop Inc. | 1-cyclopropyl-4-pyridyl-quinolinones |
| GB9226855D0 (en) * | 1992-12-23 | 1993-02-17 | Erba Carlo Spa | Vinylene-azaindole derivatives and process for their preparation |
| US5582995A (en) | 1993-06-11 | 1996-12-10 | The General Hospital Corporation | Methods of screening for compounds which inhibit the direct binding of Ras to Raf |
| JP2944048B2 (ja) * | 1993-07-06 | 1999-08-30 | フアイザー・インコーポレイテツド | 二環式テトラヒドロピラゾロピリジン |
| US5645982A (en) * | 1993-08-19 | 1997-07-08 | Systemix, Inc. | Method for screening potential therapeutically effective antiviral agents |
| GB9501567D0 (en) * | 1995-01-26 | 1995-03-15 | Pharmacia Spa | Hydrosoluble 3-arylidene-2-oxindole derivatives as tyrosine kinase inhibitors |
| US5880141A (en) * | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
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