ES2640386T3 - Potenciador de inhibidores del homólogo Zeste 2 - Google Patents
Potenciador de inhibidores del homólogo Zeste 2 Download PDFInfo
- Publication number
- ES2640386T3 ES2640386T3 ES14741958.4T ES14741958T ES2640386T3 ES 2640386 T3 ES2640386 T3 ES 2640386T3 ES 14741958 T ES14741958 T ES 14741958T ES 2640386 T3 ES2640386 T3 ES 2640386T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- nrarb
- heterocycloalkyl
- cycloalkyl
- aryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000003112 inhibitor Substances 0.000 title description 30
- 239000003623 enhancer Substances 0.000 title description 3
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- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 122
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Epidemiology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361844540P | 2013-07-10 | 2013-07-10 | |
| US201361844540P | 2013-07-10 | ||
| PCT/IB2014/062983 WO2015004618A1 (en) | 2013-07-10 | 2014-07-09 | Enhancer of zeste homolog 2 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2640386T3 true ES2640386T3 (es) | 2017-11-02 |
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|---|---|---|---|
| ES14741958.4T Active ES2640386T3 (es) | 2013-07-10 | 2014-07-09 | Potenciador de inhibidores del homólogo Zeste 2 |
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| Country | Link |
|---|---|
| US (1) | US9556157B2 (enExample) |
| EP (1) | EP3019494B1 (enExample) |
| JP (1) | JP2016523955A (enExample) |
| KR (1) | KR20160030221A (enExample) |
| CN (1) | CN105473580A (enExample) |
| AU (1) | AU2014288839B2 (enExample) |
| CA (1) | CA2917463A1 (enExample) |
| ES (1) | ES2640386T3 (enExample) |
| RU (1) | RU2016104044A (enExample) |
| WO (1) | WO2015004618A1 (enExample) |
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| BR112015008447A2 (pt) | 2012-10-15 | 2017-07-04 | Epizyme Inc | métodos para tratar câncer |
| WO2014100665A1 (en) | 2012-12-21 | 2014-06-26 | Epizyme, Inc. | 1,4-pyridone bicyclic heteroaryl compounds |
| KR20170068603A (ko) * | 2014-10-28 | 2017-06-19 | 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 | 제스트 인핸서 상동체 2 억제제 |
| TW201636344A (zh) | 2014-12-05 | 2016-10-16 | 美國禮來大藥廠 | Ｅｚｈ２抑制劑 |
| UY36758A (es) * | 2015-06-30 | 2016-12-30 | Glaxosmithkline Ip No 2 Ltd | Inhibidores del potenciador del homólogo zeste 2 |
| 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 |
| EP3370725A4 (en) * | 2015-11-06 | 2019-07-03 | Epizyme, Inc. | PEDIATRIC DOSAGE FOR THE TREATMENT OF CANCER WITH AN EZH2 INHIBITOR |
| WO2018058029A1 (en) | 2016-09-26 | 2018-03-29 | Dana-Farber Cancer Institute, Inc. | Chromobox protein inhibitors and uses thereof |
| CA3050221C (en) | 2017-01-19 | 2021-09-28 | Daiichi Sankyo Company, Limited | Pharmaceutical composition used for treatment of htlv-1-associated myelopathy |
| US10266542B2 (en) | 2017-03-15 | 2019-04-23 | Mirati Therapeutics, Inc. | EZH2 inhibitors |
| FI4043466T3 (fi) | 2018-01-31 | 2024-10-30 | Mirati Therapeutics Inc | Prc2:n estäjiä |
| CA3104209A1 (en) | 2018-07-09 | 2020-01-16 | Fondation Asile Des Aveugles | Inhibition of prc2 subunits to treat eye disorders |
| JP7624404B2 (ja) | 2019-04-22 | 2025-01-30 | ミラティ セラピューティクス，インク． | Ｐｒｃ２阻害剤としてのナフチリジン誘導体 |
| WO2020247475A1 (en) | 2019-06-05 | 2020-12-10 | Mirati Therapeutics, Inc. | Imidazo[1,2-c]pyrimidine derivatives as prc2 inhibitors for treating cancer |
| 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 |
| IL316421A (en) | 2022-04-27 | 2024-12-01 | Daiichi Sankyo Co Ltd | Combination of an antibody-drug conjugate with an EZH1 and/or EZH2 inhibitor |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6559145B2 (en) | 2000-07-12 | 2003-05-06 | Pharmacia & Upjohn Company | Heterocycle carboxamides as antiviral agents |
| PL211300B1 (pl) | 2002-04-17 | 2012-05-31 | Cytokinetics Inc | Związek i kompozycja zawierająca ten związek |
| US7618981B2 (en) | 2004-05-06 | 2009-11-17 | Cytokinetics, Inc. | Imidazopyridinyl-benzamide anti-cancer agents |
| US8163749B2 (en) | 2005-12-14 | 2012-04-24 | Bristol-Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| HRP20170736T1 (hr) | 2010-05-07 | 2017-07-28 | Glaxosmithkline Llc | Indoli |
| ES2534804T3 (es) | 2010-05-07 | 2015-04-28 | Glaxosmithkline Llc | Indazoles |
| ES2528269T3 (es) | 2010-05-07 | 2015-02-06 | Glaxosmithkline Llc | Azaindazoles |
| EP2646020B1 (en) | 2010-12-01 | 2016-09-21 | Glaxosmithkline LLC | Indoles |
| 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 |
| EP2780013A4 (en) * | 2011-11-18 | 2015-07-01 | Constellation Pharmaceuticals Inc | MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF |
| EP2812001B1 (en) | 2012-02-10 | 2017-06-14 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| 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 |
| RU2699546C2 (ru) | 2012-04-13 | 2019-09-06 | Эпизайм, Инк. | Комбинированная терапия для лечения рака |
| WO2013173441A2 (en) | 2012-05-16 | 2013-11-21 | Glaxosmithkline Llc | Enhancer of zeste homolog 2 inhibitors |
| SG10201705989YA (en) | 2012-10-15 | 2017-08-30 | Epizyme Inc | Substituted benzene compounds |
| KR20150095779A (ko) | 2012-12-13 | 2015-08-21 | 글락소스미스클라인 엘엘씨 | 제스트 인핸서 상동체 2 억제제 |
| WO2014100665A1 (en) * | 2012-12-21 | 2014-06-26 | Epizyme, Inc. | 1,4-pyridone bicyclic heteroaryl compounds |
| CA2910873A1 (en) | 2013-04-30 | 2014-11-06 | Glaxosmithkline Intellectual Property (No.2) Limited | Enhancer of zeste homolog 2 inhibitors |
| US10150764B2 (en) | 2013-07-19 | 2018-12-11 | Epizyme, Inc. | Substituted benzene compounds |
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2014
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- 2014-07-09 US US14/898,178 patent/US9556157B2/en not_active Expired - Fee Related
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| US20160130261A1 (en) | 2016-05-12 |
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| CN105473580A (zh) | 2016-04-06 |
| US9556157B2 (en) | 2017-01-31 |
| CA2917463A1 (en) | 2015-01-15 |
| KR20160030221A (ko) | 2016-03-16 |
| AU2014288839A1 (en) | 2016-01-28 |
| RU2016104044A (ru) | 2017-08-15 |
| EP3019494B1 (en) | 2017-06-21 |
| EP3019494A1 (en) | 2016-05-18 |
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