ES2948442T3 - Inhibidores de EZH2 para el tratamiento de linfoma - Google Patents
Inhibidores de EZH2 para el tratamiento de linfoma Download PDFInfo
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- ES2948442T3 ES2948442T3 ES15809540T ES15809540T ES2948442T3 ES 2948442 T3 ES2948442 T3 ES 2948442T3 ES 15809540 T ES15809540 T ES 15809540T ES 15809540 T ES15809540 T ES 15809540T ES 2948442 T3 ES2948442 T3 ES 2948442T3
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- ezh2
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- ezh2 inhibitor
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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
- A61K31/435—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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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
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| PCT/US2015/036310 WO2015195848A1 (en) | 2014-06-17 | 2015-06-17 | Ezh2 inhibitors for treating lymphoma |
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| US20130102477A1 (en) | 2010-06-23 | 2013-04-25 | Ryan D. Morin | Biomarkers for non-hodgkin lymphomas and uses thereof |
| JO3438B1 (ar) | 2011-04-13 | 2019-10-20 | Epizyme Inc | مركبات بنزين مستبدلة بأريل أو أريل غير متجانس |
| BR112015008447A2 (pt) | 2012-10-15 | 2017-07-04 | Epizyme Inc | métodos para tratar câncer |
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| KR20230031963A (ko) | 2014-06-17 | 2023-03-07 | 에피자임, 인코포레이티드 | 림프종 치료를 위한 ｅｚｈ2 억제제 |
| CN106794177A (zh) | 2014-10-16 | 2017-05-31 | Epizyme股份有限公司 | 治疗癌症的方法 |
| KR20240035908A (ko) * | 2014-11-17 | 2024-03-18 | 에피자임, 인코포레이티드 | 암을 치료하기 위한 방법 |
| TW201636344A (zh) | 2014-12-05 | 2016-10-16 | 美國禮來大藥廠 | Ｅｚｈ２抑制劑 |
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| CA2988816A1 (en) * | 2015-06-10 | 2016-12-15 | Epizyme, Inc. | Ezh2 inhibitors for treating lymphoma |
| US10493076B2 (en) | 2015-08-24 | 2019-12-03 | Epizyme, Inc. | Method for treating cancer |
| TW201718598A (zh) | 2015-08-27 | 2017-06-01 | 美國禮來大藥廠 | Ｅｚｈ２抑制劑 |
| US11951108B2 (en) | 2016-01-29 | 2024-04-09 | Epizyme, Inc. | Combination therapy for treating cancer |
| JP7121660B2 (ja) | 2016-06-01 | 2022-08-18 | エピザイム，インコーポレイティド | 癌を処置するためのｅｚｈ２阻害剤の使用 |
| MA45406A (fr) | 2016-06-17 | 2019-04-24 | Epizyme Inc | Inhibiteurs d'ezh2 pour traiter le cancer |
| WO2018136596A1 (en) * | 2017-01-20 | 2018-07-26 | Constellation Pharmaceuticals, Inc. | Solid dispersions of (r)-n-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1h-indole-3-carboxamide |
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| JP2020522687A (ja) | 2017-06-02 | 2020-07-30 | エピザイム，インコーポレイティド | 癌を処置するためのｅｚｈ２阻害剤の使用 |
| US20210161883A1 (en) * | 2017-07-10 | 2021-06-03 | Constellation Pharmaceuticals, Inc. | Ezh2 inhibitor-induced gene expression |
| CA3074720A1 (en) | 2017-09-05 | 2019-03-14 | Epizyme, Inc. | Combination therapy for treating cancer |
| JP2022545467A (ja) * | 2019-08-22 | 2022-10-27 | ジュノー セラピューティクス インコーポレイテッド | Ｔ細胞療法とｚｅｓｔｅホモログ２エンハンサー（ＥＺＨ２）阻害剤との併用療法および関連方法 |
| CN110950834A (zh) * | 2019-11-26 | 2020-04-03 | 济南大学 | 新型eed-ezh2相互作用小分子抑制剂的确定和评价 |
| CN110960525A (zh) * | 2019-11-26 | 2020-04-07 | 济南大学 | 新型eed-ezh2相互作用抑制剂的确定和评价 |
| WO2021243060A1 (en) * | 2020-05-28 | 2021-12-02 | Epizyme, Inc. | Use of ezh2 inhibitors for treating cancer |
| 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 |
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|---|---|---|---|---|
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US7229774B2 (en) | 2001-08-02 | 2007-06-12 | Regents Of The University Of Michigan | Expression profile of prostate cancer |
| US9175331B2 (en) | 2010-09-10 | 2015-11-03 | Epizyme, Inc. | Inhibitors of human EZH2, and methods of use thereof |
| JP6389036B2 (ja) * | 2010-09-10 | 2018-09-12 | エピザイム インコーポレイテッド | ヒトｅｚｈ２の阻害剤、およびその使用方法 |
| EP3323820B1 (en) | 2011-02-28 | 2023-05-10 | Epizyme, Inc. | Substituted 6,5-fused bicyclic heteroaryl compounds |
| JO3438B1 (ar) | 2011-04-13 | 2019-10-20 | Epizyme Inc | مركبات بنزين مستبدلة بأريل أو أريل غير متجانس |
| TW201733984A (zh) | 2011-04-13 | 2017-10-01 | 雅酶股份有限公司 | 經取代之苯化合物 |
| CN103987842A (zh) | 2011-09-30 | 2014-08-13 | 葛兰素史密斯克莱有限责任公司 | 治疗癌症的方法 |
| CA2867282C (en) * | 2012-03-12 | 2024-04-02 | Epizyme, Inc. | Inhibitors of human ezh2, and methods of use thereof |
| RU2699546C2 (ru) | 2012-04-13 | 2019-09-06 | Эпизайм, Инк. | Комбинированная терапия для лечения рака |
| PL3184523T3 (pl) | 2012-04-13 | 2019-12-31 | Epizyme Inc | Bromowodorek N-((4,6-dimetylo-2-okso-1,2-dihydropirydyn-3-ylo)metylo)-5- (etylo(tetrahydro-2H-piran-4-ylo)amino)-4-metylo-4'-(morfolinometylo)-[1,1'- bifenylo]-3-karboksyamidu do zastosowania w leczeniu zaburzenia proliferacji komórkowej układu hematologicznego |
| WO2013173441A2 (en) | 2012-05-16 | 2013-11-21 | Glaxosmithkline Llc | Enhancer of zeste homolog 2 inhibitors |
| BR112015008447A2 (pt) | 2012-10-15 | 2017-07-04 | Epizyme Inc | métodos para tratar câncer |
| SG10201705989YA (en) | 2012-10-15 | 2017-08-30 | Epizyme Inc | Substituted benzene compounds |
| US20150283142A1 (en) | 2013-03-15 | 2015-10-08 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| US20140120083A1 (en) | 2012-11-01 | 2014-05-01 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| WO2014071109A1 (en) | 2012-11-01 | 2014-05-08 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| US20150313906A1 (en) | 2012-12-19 | 2015-11-05 | Glaxosmithkline Llc | Combination |
| EP2935214B1 (en) | 2012-12-21 | 2019-02-20 | Epizyme, Inc. | 1,4-pyridone compounds |
| WO2014100665A1 (en) | 2012-12-21 | 2014-06-26 | Epizyme, Inc. | 1,4-pyridone bicyclic heteroaryl compounds |
| WO2014144747A1 (en) | 2013-03-15 | 2014-09-18 | Epizyme, Inc. | Substituted 6,5-fused bicyclic heteroaryl compounds |
| CA2903572A1 (en) | 2013-03-15 | 2014-10-23 | Epizyme, Inc. | Substituted benzene compounds |
| US20140377258A1 (en) * | 2013-05-30 | 2014-12-25 | Infinity Pharmaceuticals, Inc. | Treatment Of Cancers Using PI3 Kinase Isoform Modulators |
| US9624205B2 (en) | 2013-07-19 | 2017-04-18 | Epizyme, Inc. | Substituted 6,5-fused bicyclic heteroaryl compounds |
| US10150764B2 (en) | 2013-07-19 | 2018-12-11 | Epizyme, Inc. | Substituted benzene compounds |
| CN105593378B (zh) | 2013-10-09 | 2019-09-20 | 豪夫迈·罗氏有限公司 | 用于在人ezh2基因中检测突变的方法和组合物 |
| EP4324525A3 (en) | 2013-10-16 | 2024-07-17 | Epizyme, Inc. | Hydrochloride salt form for ezh2 inhibition |
| US20160228447A1 (en) | 2013-10-18 | 2016-08-11 | Epizyme, Inc. | Method of treating cancer |
| WO2015085325A1 (en) | 2013-12-06 | 2015-06-11 | Epizyme, Inc. | Combination therapy for treating cancer |
| KR20230031963A (ko) | 2014-06-17 | 2023-03-07 | 에피자임, 인코포레이티드 | 림프종 치료를 위한 ｅｚｈ2 억제제 |
| CN107249593A (zh) | 2014-11-06 | 2017-10-13 | 达纳-法伯癌症研究所股份有限公司 | 调节染色质结构的组合物用于移植物抗宿主疾病(gvhd)的用途 |
| KR20240035908A (ko) | 2014-11-17 | 2024-03-18 | 에피자임, 인코포레이티드 | 암을 치료하기 위한 방법 |
| JP6544507B2 (ja) | 2015-02-09 | 2019-07-17 | 日本精機株式会社 | ヘッドアップディスプレイ装置 |
| CA2988816A1 (en) | 2015-06-10 | 2016-12-15 | Epizyme, Inc. | Ezh2 inhibitors for treating lymphoma |
| KR20170095656A (ko) | 2016-02-15 | 2017-08-23 | 동부대우전자 주식회사 | 방열구조를 갖는 세탁기 |
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