EA037738B1 - Кристаллические формы ингибиторов глутаминазы - Google Patents
Кристаллические формы ингибиторов глутаминазы Download PDFInfo
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- EA037738B1 EA037738B1 EA201790337A EA201790337A EA037738B1 EA 037738 B1 EA037738 B1 EA 037738B1 EA 201790337 A EA201790337 A EA 201790337A EA 201790337 A EA201790337 A EA 201790337A EA 037738 B1 EA037738 B1 EA 037738B1
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- cancer
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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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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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
- A61K31/41—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
- A61K31/433—Thidiazoles
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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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
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Medicinal Chemistry (AREA)
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- Immunology (AREA)
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- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
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| US201462034547P | 2014-08-07 | 2014-08-07 | |
| PCT/US2015/044301 WO2016022969A1 (en) | 2014-08-07 | 2015-08-07 | Crystal forms of glutaminase inhibitors |
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| EA201790337A1 EA201790337A1 (ru) | 2017-09-29 |
| EA037738B1 true EA037738B1 (ru) | 2021-05-17 |
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| EA201790337A EA037738B1 (ru) | 2014-08-07 | 2015-08-07 | Кристаллические формы ингибиторов глутаминазы |
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| MX (1) | MX2017001620A (enExample) |
| SG (1) | SG11201700816YA (enExample) |
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| LT2420498T (lt) | 2006-09-26 | 2017-10-25 | Celgene Corporation | 5-pakeistieji chinazolinono dariniai, kaip priešvėžiniai agentai |
| EA026100B1 (ru) | 2011-03-11 | 2017-03-31 | Селджин Корпорейшн | Твердые формы 3-(5-амино-2-метил-4-оксо-4н-хиназолин-3-ил)пиперидин-2,6-диона и их фармацевтические композиции и применение |
| US8604016B2 (en) | 2011-11-21 | 2013-12-10 | Calithera Biosciences Inc. | Heterocyclic inhibitors of glutaminase |
| WO2014039421A1 (en) | 2012-09-04 | 2014-03-13 | Celgene Corporation | Isotopologues of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4h)-yl) piperidine-2-6-dione and methods of preparation thereof |
| PT2920168T (pt) | 2012-11-16 | 2021-10-18 | Calithera Biosciences Inc | Inibidores heterocíclicos de glutaminase |
| EA036001B1 (ru) | 2014-06-13 | 2020-09-11 | Калитера Байосайенсиз, Инк. | Комбинация эрлотиниба и ингибитора глутаминазы для лечения рака легких |
| CA2957225A1 (en) | 2014-08-07 | 2016-02-11 | Calithera Biosciences, Inc. | Crystal forms of glutaminase inhibitors |
| EP3277276B1 (en) * | 2015-03-30 | 2020-11-04 | Calithera Biosciences, Inc. | Methods of administering glutaminase inhibitors |
| SG11201708153XA (en) | 2015-04-06 | 2017-11-29 | Calithera Biosciences Inc | Treatment of lung cancer with inhibitors of glutaminase |
| JP6971239B2 (ja) | 2015-10-05 | 2021-11-24 | キャリセラ バイオサイエンシーズ， インコーポレイテッド | グルタミナーゼ阻害剤とイムノオンコロジー薬剤との併用療法 |
| US10278968B2 (en) | 2016-08-25 | 2019-05-07 | Calithera Biosciences, Inc. | Combination therapy with glutaminase inhibitors |
| CN109982703A (zh) | 2016-08-25 | 2019-07-05 | 卡利泰拉生物科技公司 | 用谷氨酰胺酶抑制剂的组合疗法 |
| WO2019089854A1 (en) * | 2017-10-31 | 2019-05-09 | President And Fellows Of Harvard College | Methods and compositions for treating acute myeloid leukemia |
| JP2022528355A (ja) * | 2019-03-26 | 2022-06-10 | トニックス ファーマ ホールディングス リミテッド | Ｓ－（ｎ，ｎ－ジエチルカルバモイル）グルタチオンの塩形態 |
| CN114295836B (zh) * | 2021-12-22 | 2024-12-31 | 融智生物科技（青岛）有限公司 | 一种计算设备、存储介质和胶质瘤idh分型检测装置及系统 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013078123A1 (en) * | 2011-11-21 | 2013-05-30 | Calithera Biosciences Inc. | Heterocyclic inhibitors of glutaminase |
| US20130157998A1 (en) * | 2011-11-21 | 2013-06-20 | Calithera Biosciences Inc. | Heterocyclic inhibitors of glutaminase |
| WO2014078645A1 (en) * | 2012-11-16 | 2014-05-22 | Calithera Biosciences, Inc. | Heterocyclic glutaminase inhibitors |
| WO2014089048A1 (en) * | 2012-12-03 | 2014-06-12 | Calithera Biosciences, Inc. | Treatment of cancer with heterocyclic inhibitors of glutaminase |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1019519A (en) | 1911-07-11 | 1912-03-05 | Oscar Martin Polin | Apparatus for making backing for teeth. |
| US4172896A (en) | 1978-06-05 | 1979-10-30 | Dainippon Pharmaceutical Co., Ltd. | Methane-sulfonamide derivatives, the preparation thereof and composition comprising the same |
| GB9217295D0 (en) | 1992-08-14 | 1992-09-30 | Wellcome Found | Controlled released tablets |
| GB9315856D0 (en) | 1993-07-30 | 1993-09-15 | Wellcome Found | Stabilized pharmaceutical |
| US5541231A (en) | 1993-07-30 | 1996-07-30 | Glaxo Wellcome Inc. | Stabilized Pharmaceutical |
| US5358970A (en) | 1993-08-12 | 1994-10-25 | Burroughs Wellcome Co. | Pharmaceutical composition containing bupropion hydrochloride and a stabilizer |
| ATE391492T1 (de) | 1997-07-29 | 2008-04-15 | Alcon Lab Inc | Ophthalmische zusammensetzungen enthaltend galaktomannanpolymere und borat |
| US5955476A (en) | 1997-11-18 | 1999-09-21 | Celgene Corporation | Substituted 2-(2,6-dioxo-3-fluoropiperidin-3-yl)-isoindolines and method of reducing inflammatory cytokine levels |
| EP1051167A1 (en) | 1998-01-29 | 2000-11-15 | Sepracor, Inc. | Pharmaceutical uses of optically pure (-) -bupropion |
| US8889112B2 (en) | 1999-09-16 | 2014-11-18 | Ocularis Pharma, Llc | Ophthalmic formulations including selective alpha 1 antagonists |
| US6451828B1 (en) | 2000-08-10 | 2002-09-17 | Elan Pharmaceuticals, Inc. | Selective inhibition of glutaminase by bis-thiadiazoles |
| AU2002305926A1 (en) | 2001-02-05 | 2002-10-08 | Exegenics Inc. | Cysteine protease inhibitors |
| US6933289B2 (en) | 2003-07-01 | 2005-08-23 | Allergan, Inc. | Inhibition of irritating side effects associated with use of a topical ophthalmic medication |
| ES2593113T3 (es) | 2003-08-07 | 2016-12-05 | Allergan, Inc. | Composiciones para el suministro de agentes terapéuticos en los ojos y métodos para obtener y usar los mismos |
| US20050059744A1 (en) | 2003-09-12 | 2005-03-17 | Allergan, Inc. | Methods and compositions for the treatment of pain and other alpha 2 adrenergic-mediated conditions |
| JP4885122B2 (ja) | 2004-04-15 | 2012-02-29 | ユニバーシティ オブ フロリダ リサーチ ファンデーション インコーポレーティッド | 癌、器官傷害、および筋肉リハビリテーション／運動過剰訓練についての診断の生物マーカーとしてのタンパク質分解マーカー |
| RU2009114159A (ru) | 2006-09-15 | 2010-10-20 | Селджин Корпорейшн (Us) | N-метиламинометилизоидольные соединения, композиции, включающие их, и способы их применения |
| ES2401557T3 (es) | 2007-08-02 | 2013-04-22 | Amgen, Inc | Moduladores de Pl3 cinasas y métodos de uso |
| CN101951930A (zh) | 2008-02-19 | 2011-01-19 | 阿奈斯特药品株式会社 | 对身体功能的恢复有用的口服或经肠组合物 |
| WO2010093434A1 (en) | 2009-02-11 | 2010-08-19 | Celgene Corporation | Isotopologues of lenalidomide |
| EP2396313A1 (en) | 2009-02-11 | 2011-12-21 | Celgene Corporation | Isotopologues of thalidomide |
| PL2536706T3 (pl) | 2010-02-11 | 2017-10-31 | Celgene Corp | Pochodne arylometoksyizoindoliny i zawierające je kompozycje oraz sposoby ich zastosowania |
| US20130109643A1 (en) | 2010-05-10 | 2013-05-02 | The Johns Hopkins University | Metabolic inhibitor against tumors having an idh mutation |
| US10064885B2 (en) | 2010-07-09 | 2018-09-04 | Massachusetts Institute Of Technology | Metabolic gene, enzyme, and flux targets for cancer therapy |
| US20120302605A1 (en) | 2010-11-18 | 2012-11-29 | Deuteria Pharmaceuticals, Llc | 3-deutero-pomalidomide |
| WO2012097116A2 (en) | 2011-01-14 | 2012-07-19 | Celgene Corporation | Isotopologues of isoindole derivatives |
| CA2742342A1 (en) | 2011-02-12 | 2012-08-12 | Baylor Research Institute | Msh3 expression status determines the responsiveness of cancer cells to the chemotherapeutic treatment with parp inhibitors and platinum drugs |
| FI20115876A0 (fi) | 2011-09-06 | 2011-09-06 | Turun Yliopisto | Yhdistelmähoito |
| JP5712882B2 (ja) * | 2011-09-28 | 2015-05-07 | 株式会社豊田自動織機 | 電動圧縮機用の電動モータ |
| CN103030597B (zh) | 2011-09-30 | 2014-10-01 | 南昌滨西科技有限公司 | 肾脏型谷氨酰胺酶抑制剂及其制备方法和用途 |
| WO2013177426A2 (en) | 2012-05-24 | 2013-11-28 | Dana-Farber Cancer Institute, Inc. | Targeting the glutamine to pyruvate pathway for treatment of oncogenic kras-associated cancer |
| CA2884103A1 (en) | 2012-09-10 | 2014-03-13 | Celgene Corporation | Methods for the treatment of locally advanced breast cancer |
| ES2690829T3 (es) | 2012-09-17 | 2018-11-22 | Agios Pharmaceuticals, Inc. | Uso de e-cadherina y vimentina para la selección de pacientes que responden al tratamiento |
| CA2892089A1 (en) | 2012-11-21 | 2014-05-30 | Rene M. Lemieux | Glutaminase inhibitors and methods of use |
| US9029531B2 (en) | 2012-11-22 | 2015-05-12 | Agios Pharmaceuticals, Inc. | Compounds and their methods of use |
| WO2014079011A1 (en) | 2012-11-22 | 2014-05-30 | Agios Pharmaceuticals, Inc. | Heterocyclic compounds for inhibiting glutaminase and their methods of use |
| WO2015061432A1 (en) | 2013-10-25 | 2015-04-30 | Calithera Biosciences, Inc. | Treatment of viral infections with inhibitors of glutaminase |
| WO2015138902A1 (en) | 2014-03-14 | 2015-09-17 | Calithera Biosciences, Inc. | Combination therapy with glutaminase inhibitors |
| US10221459B2 (en) | 2014-05-13 | 2019-03-05 | Case Western Reserve University | Compositions and methods of treating cancer harboring PIKC3A mutations |
| EA036001B1 (ru) | 2014-06-13 | 2020-09-11 | Калитера Байосайенсиз, Инк. | Комбинация эрлотиниба и ингибитора глутаминазы для лечения рака легких |
| WO2016004418A1 (en) | 2014-07-03 | 2016-01-07 | Board Of Regents, University Of Texas System | Glutaminase inhibitor therapy |
| WO2016014890A1 (en) | 2014-07-24 | 2016-01-28 | Calithera Biosciences, Inc. | Treatment of multiple myeloma with heterocyclic inhibitors of glutaminase |
| CA2957225A1 (en) | 2014-08-07 | 2016-02-11 | Calithera Biosciences, Inc. | Crystal forms of glutaminase inhibitors |
| WO2016054388A1 (en) | 2014-10-03 | 2016-04-07 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Glutaminase inhibitors |
| US10517844B2 (en) | 2014-11-13 | 2019-12-31 | Buck Institute For Research On Aging | Inhibition of proline catabolism for the treatment of cancer and other therapeutic applications |
| EP3277276B1 (en) | 2015-03-30 | 2020-11-04 | Calithera Biosciences, Inc. | Methods of administering glutaminase inhibitors |
| SG11201708153XA (en) | 2015-04-06 | 2017-11-29 | Calithera Biosciences Inc | Treatment of lung cancer with inhibitors of glutaminase |
| JP6971239B2 (ja) | 2015-10-05 | 2021-11-24 | キャリセラ バイオサイエンシーズ， インコーポレイテッド | グルタミナーゼ阻害剤とイムノオンコロジー薬剤との併用療法 |
| US10278968B2 (en) | 2016-08-25 | 2019-05-07 | Calithera Biosciences, Inc. | Combination therapy with glutaminase inhibitors |
| CN109982703A (zh) | 2016-08-25 | 2019-07-05 | 卡利泰拉生物科技公司 | 用谷氨酰胺酶抑制剂的组合疗法 |
| WO2018039442A1 (en) | 2016-08-25 | 2018-03-01 | Calithera Biosciences, Inc. | Treatment of cancer with inhibitors of glutaminase |
| KR20190125432A (ko) | 2017-03-10 | 2019-11-06 | 칼리테라 바이오사이언시즈, 인코포레이티드 | 글루타미나제 억제제를 사용하는 병용 요법 |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013078123A1 (en) * | 2011-11-21 | 2013-05-30 | Calithera Biosciences Inc. | Heterocyclic inhibitors of glutaminase |
| US20130157998A1 (en) * | 2011-11-21 | 2013-06-20 | Calithera Biosciences Inc. | Heterocyclic inhibitors of glutaminase |
| WO2014078645A1 (en) * | 2012-11-16 | 2014-05-22 | Calithera Biosciences, Inc. | Heterocyclic glutaminase inhibitors |
| WO2014089048A1 (en) * | 2012-12-03 | 2014-06-12 | Calithera Biosciences, Inc. | Treatment of cancer with heterocyclic inhibitors of glutaminase |
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| EA201790337A1 (ru) | 2017-09-29 |
| MX2017001620A (es) | 2017-05-10 |
| JP2017523991A (ja) | 2017-08-24 |
| EP3193876A4 (en) | 2017-12-27 |
| CN106999490A (zh) | 2017-08-01 |
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| IL250391A0 (en) | 2017-03-30 |
| EP3193876A1 (en) | 2017-07-26 |
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| SG11201700816YA (en) | 2017-02-27 |
| IL250391B (en) | 2021-10-31 |
| AU2015300825B2 (en) | 2019-10-10 |
| KR20170082494A (ko) | 2017-07-14 |
| US20190359607A1 (en) | 2019-11-28 |
| AU2019284149A1 (en) | 2020-01-30 |
| US10676472B2 (en) | 2020-06-09 |
| WO2016022969A1 (en) | 2016-02-11 |
| BR112017002403A2 (pt) | 2017-12-05 |
| JP6889101B2 (ja) | 2021-06-18 |
| JP2021165286A (ja) | 2021-10-14 |
| US20170226101A1 (en) | 2017-08-10 |
| US10316030B2 (en) | 2019-06-11 |
| CA2957225A1 (en) | 2016-02-11 |
| JP2020037588A (ja) | 2020-03-12 |
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