JP6362610B2 - 治療用化合物及び組成物並びにｐｋｍ２調節剤としてのそれらの使用 - Google Patents
治療用化合物及び組成物並びにｐｋｍ２調節剤としてのそれらの使用 Download PDFInfo
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- JP6362610B2 JP6362610B2 JP2015541933A JP2015541933A JP6362610B2 JP 6362610 B2 JP6362610 B2 JP 6362610B2 JP 2015541933 A JP2015541933 A JP 2015541933A JP 2015541933 A JP2015541933 A JP 2015541933A JP 6362610 B2 JP6362610 B2 JP 6362610B2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epidemiology (AREA)
- Enzymes And Modification Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
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| US201261724266P | 2012-11-08 | 2012-11-08 | |
| US61/724,266 | 2012-11-08 | ||
| PCT/US2013/069193 WO2014074848A1 (en) | 2012-11-08 | 2013-11-08 | Therapeutic compounds and compositions and their use as pkm2 modulators |
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| JP2016501189A JP2016501189A (ja) | 2016-01-18 |
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| US (1) | US9458132B2 (enExample) |
| EP (1) | EP2917207A1 (enExample) |
| JP (1) | JP6362610B2 (enExample) |
| KR (1) | KR20150080619A (enExample) |
| CN (1) | CN104822672B (enExample) |
| AU (1) | AU2013342203B2 (enExample) |
| CA (1) | CA2890664A1 (enExample) |
| EA (1) | EA032007B1 (enExample) |
| HK (1) | HK1213888A1 (enExample) |
| MX (1) | MX2015005841A (enExample) |
| NZ (1) | NZ707778A (enExample) |
| WO (1) | WO2014074848A1 (enExample) |
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| ES2644758T3 (es) | 2012-10-16 | 2017-11-30 | Tolero Pharmaceuticals, Inc. | Moduladores de PKM2 y métodos para su uso |
| CA2900652C (en) | 2013-02-15 | 2021-05-04 | Kala Pharmaceuticals, Inc. | Therapeutic compounds and uses thereof |
| US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
| KR102277833B1 (ko) | 2013-02-20 | 2021-07-14 | 칼라 파마슈티컬스, 인크. | 치료 화합물 및 그의 용도 |
| EP3062618B1 (en) | 2013-11-01 | 2020-02-05 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| US9890173B2 (en) | 2013-11-01 | 2018-02-13 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| CN104817490B (zh) * | 2015-05-13 | 2017-10-13 | 北京大学 | 氨基二硫代甲酸酯类化合物及其制备方法与应用 |
| WO2017095751A1 (en) | 2015-12-02 | 2017-06-08 | Partikula Llc | Compositions and methods for modulating cancer cell metabolism |
| CA3252823A1 (en) | 2016-06-13 | 2025-02-25 | Gilead Sciences, Inc. | Fxr (nr1h4) modulating compounds |
| US10392399B2 (en) | 2016-09-08 | 2019-08-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| AU2017324251A1 (en) | 2016-09-08 | 2019-03-21 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| EP3509422A4 (en) | 2016-09-08 | 2020-05-20 | Kala Pharmaceuticals, Inc. | CRYSTALLINE FORMS OF THERAPEUTIC COMPOUNDS AND USES THEREOF |
| HUE045261T2 (hu) | 2017-03-20 | 2019-12-30 | Forma Therapeutics Inc | Pirrolopirrol kompozíciók piruvát kináz (PKR) aktivátorokként |
| US11364240B2 (en) * | 2017-08-15 | 2022-06-21 | Agios Pharmaceuticals, Inc. | Pyruvate kinase activators for use in treating blood disorders |
| WO2019075367A1 (en) | 2017-10-13 | 2019-04-18 | Tolero Pharmaceuticals, Inc. | PKM2 ACTIVATORS IN COMBINATION WITH OXYGEN REACTIVE SPECIES FOR THE TREATMENT OF CANCER |
| CN113166060B (zh) * | 2018-09-19 | 2024-01-09 | 诺沃挪第克健康护理股份公司 | 用丙酮酸激酶激活化合物治疗镰状细胞病 |
| US12122778B2 (en) | 2018-09-19 | 2024-10-22 | Novo Nordisk Health Care Ag | Activating pyruvate kinase R |
| CA3129949C (en) | 2019-02-19 | 2024-04-30 | Gilead Sciences, Inc. | Solid forms of fxr agonists |
| JP7547360B2 (ja) | 2019-03-22 | 2024-09-09 | スミトモ ファーマ オンコロジー， インコーポレイテッド | Ｐｋｍ２モジュレーターを含む組成物およびそれを使用する処置の方法 |
| ES3042390T3 (en) | 2019-09-19 | 2025-11-20 | Novo Nordisk Healthcare Ag | Pyruvate kinase r (pkr) activating compositions |
| US11566030B2 (en) | 2021-02-08 | 2023-01-31 | Global Blood Therapeutics, Inc. | Substituted 2,6-dihydropyrrolo[3,4-c]pyrazoles as pyruvate kinase activators |
| US12128035B2 (en) | 2021-03-19 | 2024-10-29 | Novo Nordisk Health Care Ag | Activating pyruvate kinase R |
Family Cites Families (16)
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| US6214879B1 (en) | 1998-03-24 | 2001-04-10 | Virginia Commonwealth University | Allosteric inhibitors of pyruvate kinase |
| KR100692232B1 (ko) | 1999-09-04 | 2007-03-09 | 아스트라제네카 아베 | 피루베이트 탈수소효소 활성을 증가시키는 치환된 ｎ-페닐2-히드록시-2-메틸-3,3,3-트리플루오로프로판아미드 유도체 |
| JP2008514590A (ja) | 2004-09-24 | 2008-05-08 | アストラゼネカ・アクチエボラーグ | ベンゾイミダゾール誘導体、それを含む組成物、その製造方法及びその使用 |
| EP3173415B1 (en) * | 2008-10-09 | 2019-06-05 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Activators of human pyruvate kinase |
| CA2755394C (en) | 2009-03-13 | 2021-10-19 | Agios Pharmaceuticals, Inc. | Methods and compositions for cell-proliferation-related disorders |
| CA2758071C (en) | 2009-04-06 | 2018-01-09 | Agios Pharmaceuticals, Inc. | Pyruvate kinase m2 modulators, therapeutic compositions and related methods of use |
| AR076380A1 (es) | 2009-04-22 | 2011-06-08 | Janssen Pharmaceutica Nv | Azetidinil diamidas inhibidoras de monoacilglicerol lipasa(mgl), composiciones farmaceuticas que las contienen y uso de las mismas para el tratamiento de enfermedades y patologias que incluyen dolor inflamatorio. |
| EP2448581B1 (en) * | 2009-06-29 | 2016-12-07 | Agios Pharmaceuticals, Inc. | Therapeutic compositions and related methods of use |
| BRPI1011587B1 (pt) | 2009-06-29 | 2020-03-24 | Agios Pharmaceuticals, Inc. | Compostos de quinolina sulfonamida com atividade moduladora de pmk2 e uso dos mesmos |
| US20130109672A1 (en) * | 2010-04-29 | 2013-05-02 | The United States Of America,As Represented By The Secretary, Department Of Health And Human Service | Activators of human pyruvate kinase |
| DE102010048800A1 (de) | 2010-10-20 | 2012-05-10 | Merck Patent Gmbh | Chinoxalinderivate |
| EP2651898B1 (en) * | 2010-12-17 | 2015-12-09 | Agios Pharmaceuticals, Inc. | Novel n-(4-(azetidine-1-carbonyl)phenyl)-(hetero-)arylsulfonamide derivatives as pyruvate kinase m2 (pmk2) modulators |
| TWI549947B (zh) * | 2010-12-29 | 2016-09-21 | 阿吉歐斯製藥公司 | 治療化合物及組成物 |
| US9388164B2 (en) * | 2011-05-03 | 2016-07-12 | Agios Pharmaceuticals, Inc | Methods of using pyruvate kinase activators |
| TR201809699T4 (tr) * | 2011-05-03 | 2018-07-23 | Agios Pharmaceuticals Inc | Tedavi̇de kullanilmaya yöneli̇k pi̇ruvat ki̇naz akti̇vatörleri̇. |
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| WO2014074848A1 (en) | 2014-05-15 |
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| US9458132B2 (en) | 2016-10-04 |
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| EA032007B1 (ru) | 2019-03-29 |
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