KR101342014B1 - 유사분열 진행을 억제하기 위한 화합물 - Google Patents
유사분열 진행을 억제하기 위한 화합물 Download PDFInfo
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- KR101342014B1 KR101342014B1 KR1020117022355A KR20117022355A KR101342014B1 KR 101342014 B1 KR101342014 B1 KR 101342014B1 KR 1020117022355 A KR1020117022355 A KR 1020117022355A KR 20117022355 A KR20117022355 A KR 20117022355A KR 101342014 B1 KR101342014 B1 KR 101342014B1
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Classifications
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- 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
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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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Enzymes And Modification Thereof (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104193750B (zh) | 2004-05-14 | 2018-04-27 | 千禧药品公司 | 通过抑制极光激酶抑制有丝分裂的化合物和方法 |
| CL2007003244A1 (es) * | 2006-11-16 | 2008-04-04 | Millennium Pharm Inc | Compuestos derivados de pirimido[5,4-d][2]benzazepina; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento del cancer. |
| WO2010065134A1 (en) * | 2008-12-05 | 2010-06-10 | Millennium Pharmaceuticals, Inc. | 5, 7-dihydro- 6h-pyrimido [ 5, 4-d] [ 1 ] benzazepin-6-thiones as plk inhibitors |
| MX2011006725A (es) | 2008-12-22 | 2011-09-15 | Millennium Pharm Inc | Combinacion de inhibidores de aurora cinasa y anticuerpos anti-cd20. |
| JO3635B1 (ar) * | 2009-05-18 | 2020-08-27 | Millennium Pharm Inc | مركبات صيدلانية صلبة وطرق لانتاجها |
| JO3434B1 (ar) * | 2009-07-31 | 2019-10-20 | Millennium Pharm Inc | مركبات صيدلانية لمعالجة السرطان وامراض واضطرابات اخري |
| CN104031049A (zh) * | 2010-02-19 | 2014-09-10 | 米伦纽姆医药公司 | 极光激酶抑制剂的结晶形式 |
| US20120107304A1 (en) | 2010-04-27 | 2012-05-03 | Boehringer Ingelheim International Gmbh | Combination therapy in treatment of oncological and fibrotic diseases |
| WO2011161031A1 (en) * | 2010-06-22 | 2011-12-29 | Glaxosmithkline Llc | Benzotriazolodiazepine compounds inhibitors of bromodomains |
| AR086656A1 (es) * | 2011-06-03 | 2014-01-15 | Millennium Pharm Inc | Combinacion de inhibidores de mek e inhibidores selectivos de la quinasa aurora a |
| US20130303519A1 (en) * | 2012-03-20 | 2013-11-14 | Millennium Pharmaceuticals, Inc. | Methods of treating cancer using aurora kinase inhibitors |
| CN103772391A (zh) * | 2012-10-23 | 2014-05-07 | 杨子娇 | 一类治疗房角狭窄的化合物及其用途 |
| US9724354B2 (en) | 2013-03-22 | 2017-08-08 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mTORC1/2 inhibitors and selective inhibitors of Aurora A kinase |
| WO2015085289A1 (en) | 2013-12-06 | 2015-06-11 | Millennium Pharmaceuticals, Inc. | Combination of aurora kinase inhibitors and anti-cd30 antibodies |
| CA2972076A1 (en) * | 2014-12-23 | 2016-06-30 | Millennium Pharmaceuticals, Inc. | Combination of raf inhibitors and aurora kinase inhibitors |
| JP2018524292A (ja) | 2015-07-21 | 2018-08-30 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | オーロラキナーゼインヒビターと化学療法剤の投与 |
| CA2997769A1 (en) | 2015-09-09 | 2017-03-16 | Icahn School Of Medicine At Mount Sinai | Heterocyclic constrained tricyclic sulfonamides as anti-cancer agents |
| CN108349961B (zh) | 2015-09-09 | 2022-02-18 | 西奈山伊坎医学院 | 杂环受限三环磺酰胺作为抗癌试剂 |
| US11340215B2 (en) | 2016-02-26 | 2022-05-24 | Japanese Foundation For Cancer Research | Screening method of anticancer agent focused on function of HP1 and evaluation system |
| CN109195593A (zh) | 2016-03-15 | 2019-01-11 | 奥莱松基因组股份有限公司 | 用于治疗实体瘤的lsd1抑制剂的组合 |
| JP6188986B1 (ja) * | 2017-03-23 | 2017-08-30 | 株式会社ノエビア | 時計遺伝子発現量調整剤及びエラスチン産生促進剤 |
| WO2019195658A1 (en) | 2018-04-05 | 2019-10-10 | Dana-Farber Cancer Institute, Inc. | Sting levels as a biomarker for cancer immunotherapy |
| WO2020049208A1 (es) | 2018-09-09 | 2020-03-12 | Fundacio Privada Institut De Recerca De La Sida - Caixa | Aurora cinasa como diana para tratar, prevenir o curar una infección por vih o sida |
| US20220305048A1 (en) | 2019-08-26 | 2022-09-29 | Dana-Farber Cancer Institute, Inc. | Use of heparin to promote type 1 interferon signaling |
| WO2023196959A1 (en) | 2022-04-07 | 2023-10-12 | Eli Lilly And Company | Process for making a kras g12c inhibitor |
| WO2023196887A1 (en) | 2022-04-08 | 2023-10-12 | Eli Lilly And Company | Method of treatment including kras g12c inhibitors and aurora a inhibitors |
| IL317823A (en) | 2022-06-30 | 2025-02-01 | Lilly Co Eli | KRAS G12C inhibitor for cancer treatment |
| WO2025075211A1 (en) | 2023-10-03 | 2025-04-10 | Takeda Pharmaceutical Company Limited | Alisertib and paclitaxel for treating small cell lung cancer |
| WO2025245045A1 (en) | 2024-05-21 | 2025-11-27 | The Regents Of The University Of California | Methods of treating lung cancer |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005111039A2 (en) | 2004-05-14 | 2005-11-24 | Millennium Pharmaceuticals, Inc. | Compounds and methods for inhibiting mitotic progression by inhibition of aurora kinase |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4099012A (en) * | 1975-08-28 | 1978-07-04 | Ciba-Geigy Corporation | 2-pyrazolyl-benzophenones |
| SU1181547A3 (ru) | 1979-02-07 | 1985-09-23 | Ф.Хоффманн-Ля Рош Унд Ко,Аг (Фирма) | Способ получени пиримидо-2-бензазепинов или их фармакологически совместимых кислотно-аддитивных солей (и его вариант) |
| US4481142A (en) * | 1979-02-07 | 1984-11-06 | Hoffmann-La Roche Inc. | Pyrimido-2-benzazepines |
| US4469633A (en) * | 1980-05-16 | 1984-09-04 | Hoffmann-La Roche Inc. | N-oxides of 5-oxo-1-phenyl-2-benzazepines |
| EP0273697A3 (en) | 1986-12-30 | 1989-11-29 | Merck & Co. Inc. | 2-benzazepines with 5- and 6- membered heterocyclic rings |
| US5166151A (en) * | 1988-03-25 | 1992-11-24 | Merck & Co., Inc. | 2-Benzazepines with 5- and 6-membered heterocyclic rings, compositions and medical methods of use thereof |
| US5210082A (en) * | 1991-05-16 | 1993-05-11 | Merck & Co., Inc. | 2-benzazepines with 5- and 6-membered heterocyclic rings to treat pain and anxiety disorders |
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| AU723860B2 (en) | 1996-03-08 | 2000-09-07 | Astrazeneca Ab | Azolobenzazepine derivatives as neurologically active agents |
| AU5330698A (en) * | 1996-12-23 | 1998-07-17 | Celltech Therapeutics Limited | Fused polycyclic 2-aminopyrimidine derivatives, their preparation and their use as protein tyrosine kinase inhibitors |
| GB9713087D0 (en) | 1997-06-20 | 1997-08-27 | Celltech Therapeutics Ltd | Chemical compounds |
| TW510902B (en) * | 1997-09-29 | 2002-11-21 | Meiji Seika Kaisha | Tricyclic triazolobenzazepine derivatives, process for producing the same, and antiallergic agents |
| US6277844B1 (en) * | 1998-09-14 | 2001-08-21 | Sydney Spector | Compound for selective treatment of malignant cells by inhibiting cell cycle progression, decreasing Bcl2, and increasing apoptosis |
| US6417207B1 (en) | 1999-05-12 | 2002-07-09 | Nitromed, Inc. | Nitrosated and nitrosylated potassium channel activators, compositions and methods of use |
| AU1651201A (en) | 1999-12-06 | 2001-06-18 | Ajinomoto Co., Inc. | Amidinophenylpyruvic acid derivative |
| CN102250071A (zh) * | 2000-12-21 | 2011-11-23 | 沃泰克斯药物股份有限公司 | 可用作蛋白激酶抑制剂的吡唑化合物 |
| US6686352B2 (en) | 2001-05-18 | 2004-02-03 | Hoffmann-La Roche Inc. | Substituted imidazo [1,5-a] pyrimido [5,4-d] [1] benzazepine derivatives |
| DE10135457A1 (de) * | 2001-07-20 | 2003-02-06 | Adc Automotive Dist Control | Optische Sensoranordnung |
| AU2002328999B8 (en) | 2001-08-09 | 2008-06-05 | Actelion Pharmaceuticals Ltd. | Novel benzo-fused heterocycles as endothelin antagonists |
| CN1897950A (zh) | 2003-10-14 | 2007-01-17 | 惠氏公司 | 稠合芳基和杂芳基衍生物及其使用方法 |
| RU2007122485A (ru) | 2004-11-17 | 2008-12-27 | Мийкана Терапьютикс | Ингибиторы киназы |
| US20100160324A1 (en) | 2004-12-30 | 2010-06-24 | Astex Therapeutics Limited | Pyrazole derivatives as that modulate the activity of cdk, gsk and aurora kinases |
| ES2408318T3 (es) | 2005-12-23 | 2013-06-20 | Glaxosmithkline Llc | Inhibidores de azaindol de las cinasas Aurora |
| JP2010500352A (ja) | 2006-08-09 | 2010-01-07 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | 有糸分裂の進行を阻止するためのピリドベンゾアゼピン化合物および方法 |
| CL2007003244A1 (es) | 2006-11-16 | 2008-04-04 | Millennium Pharm Inc | Compuestos derivados de pirimido[5,4-d][2]benzazepina; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento del cancer. |
| JO3635B1 (ar) | 2009-05-18 | 2020-08-27 | Millennium Pharm Inc | مركبات صيدلانية صلبة وطرق لانتاجها |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005111039A2 (en) | 2004-05-14 | 2005-11-24 | Millennium Pharmaceuticals, Inc. | Compounds and methods for inhibiting mitotic progression by inhibition of aurora kinase |
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