ES2899461T3 - Inhibidores heterocíclicos de glutaminasa - Google Patents
Inhibidores heterocíclicos de glutaminasa Download PDFInfo
- Publication number
- ES2899461T3 ES2899461T3 ES13855039T ES13855039T ES2899461T3 ES 2899461 T3 ES2899461 T3 ES 2899461T3 ES 13855039 T ES13855039 T ES 13855039T ES 13855039 T ES13855039 T ES 13855039T ES 2899461 T3 ES2899461 T3 ES 2899461T3
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- alkyl
- cancer
- compound
- aryl
- heteroaryl
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- 108010073324 Glutaminase Proteins 0.000 title description 43
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/135—Nitrogen atoms
-
- 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
- A61K31/41—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
- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
-
- 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
- A61K31/41—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
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
-
- 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
- A61K31/41—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
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- 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
- A61K31/495—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
-
- 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
- C07D417/02—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 two hetero rings
- C07D417/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261727195P | 2012-11-16 | 2012-11-16 | |
| US201361824434P | 2013-05-17 | 2013-05-17 | |
| PCT/US2013/070277 WO2014078645A1 (en) | 2012-11-16 | 2013-11-15 | Heterocyclic glutaminase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2899461T3 true ES2899461T3 (es) | 2022-03-11 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13855039T Active ES2899461T3 (es) | 2012-11-16 | 2013-11-15 | Inhibidores heterocíclicos de glutaminasa |
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| LT (1) | LT2920168T (enExample) |
| MX (1) | MX381260B (enExample) |
| PL (1) | PL2920168T3 (enExample) |
| PT (1) | PT2920168T (enExample) |
| RS (1) | RS62447B1 (enExample) |
| SG (1) | SG11201503720SA (enExample) |
| SI (1) | SI2920168T1 (enExample) |
| SM (1) | SMT202100589T1 (enExample) |
| WO (1) | WO2014078645A1 (enExample) |
| ZA (2) | ZA201504294B (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US8604016B2 (en) | 2011-11-21 | 2013-12-10 | Calithera Biosciences Inc. | Heterocyclic inhibitors of glutaminase |
| JP6275153B2 (ja) | 2012-11-16 | 2018-02-07 | 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 | ヘテロ環式グルタミナーゼ阻害剤 |
| CA2892817A1 (en) * | 2012-12-03 | 2014-06-12 | Calithera Biosciences Inc. | Treatment of cancer with heterocyclic inhibitors of glutaminase |
| EP3092235A2 (en) | 2014-01-06 | 2016-11-16 | Rhizen Pharmaceuticals S.A. | Novel inhibitors of glutaminase |
| MX2016014143A (es) * | 2014-04-30 | 2017-02-15 | Pfizer | Derivados de diheterociclo enlazado a cicloalquilo. |
| GB201409624D0 (en) | 2014-05-30 | 2014-07-16 | Astrazeneca Ab | 1,3,4-thiadiazole compounds and their use in treating cancer |
| AU2015274361B2 (en) * | 2014-06-13 | 2020-11-05 | Calithera Biosciences, Inc. | Combination therapy with glutaminase inhibitors |
| WO2016004413A2 (en) * | 2014-07-03 | 2016-01-07 | Board Of Regents, University Of Texas System | Gls1 inhibitors for treating disease |
| ES2921989T3 (es) * | 2014-07-03 | 2022-09-05 | Univ Texas | Terapia con inhibidores de glutaminasa |
| CN107074805B (zh) | 2014-07-03 | 2021-02-26 | 德州大学系统董事会 | 用于治疗疾病的gls1抑制剂 |
| WO2016007647A1 (en) * | 2014-07-09 | 2016-01-14 | The Johns Hopkins University | Glutaminase inhibitor discovery and nanoparticle-enhanced delivery for cancer therapy |
| EA037738B1 (ru) * | 2014-08-07 | 2021-05-17 | Калитера Байосайенсиз, Инк. | Кристаллические формы ингибиторов глутаминазы |
| JP6768693B2 (ja) * | 2015-03-30 | 2020-10-14 | 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を投与する方法 |
| US10441587B2 (en) * | 2015-04-06 | 2019-10-15 | Calithera Biosciences, Inc. | Treatment of lung cancer with inhibitors of glutaminase |
| EP3316887B1 (en) | 2015-06-30 | 2020-04-08 | Board of Regents, The University of Texas System | Gls1 inhibitors for treating disease |
| WO2017062354A1 (en) | 2015-10-05 | 2017-04-13 | Calithera Biosciences, Inc. | Combination therapy with glutaminase inhibitors and immuno-oncology agents |
| US10323028B2 (en) * | 2015-11-30 | 2019-06-18 | Astrazeneca Ab | 1,3,4-thiadiazole compounds and their use in treating cancer |
| US9938265B2 (en) * | 2015-11-30 | 2018-04-10 | Astrazeneca Ab | 1,3,4-thiadiazole compounds and their use in treating cancer |
| US10150753B2 (en) | 2015-12-22 | 2018-12-11 | Board Of Regents, The University Of Texas System | Salt forms and polymorphs of (R)-1-(4-(6-(2-(4-(3,3-difluorocyclobutoxy)-6-methylpyrdin-2-yl)acetamido) pyridazin-3-yl)-2-fluorobutyl)-N-methyl-1H-1,2,3-triazole-4-carboxamide |
| 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 |
| WO2018039544A1 (en) * | 2016-08-25 | 2018-03-01 | Calithera Biosciences, Inc. | Combination therapy with glutaminase inhibitors |
| US20180055825A1 (en) * | 2016-08-25 | 2018-03-01 | Yu Liang | Treatment of cancer with inhibitors of glutaminase |
| JP7275053B2 (ja) * | 2017-06-13 | 2023-05-17 | メッドシャイン ディスカバリー インコーポレイテッド | Ｇｌｓ１阻害剤としての化合物 |
| JP7361687B2 (ja) | 2017-10-18 | 2023-10-16 | ボード オブ レジェンツ，ザ ユニバーシティ オブ テキサス システム | グルタミナーゼ阻害薬療法 |
| CN110746416A (zh) * | 2019-09-05 | 2020-02-04 | 中国药科大学 | 含有三氮唑结构的谷氨酰胺酶gls1抑制剂或其可药用的盐、其制备方法及用途 |
| CN114805346A (zh) * | 2021-07-08 | 2022-07-29 | 成都硕德药业有限公司 | 杂环类衍生物、其制备方法及用途 |
Family Cites Families (36)
| 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 |
| CN100408100C (zh) | 1997-07-29 | 2008-08-06 | 阿尔康实验室公司 | 含半乳甘露聚糖聚合物和硼酸盐的眼用组合物 |
| WO1999009825A1 (en) | 1997-08-29 | 1999-03-04 | Elan Pharmaceuticals, Inc. | Method of preventing neuronal death |
| JP2002501892A (ja) | 1998-01-29 | 2002-01-22 | セプラコア インコーポレーテッド | 光学的に純粋な（−）−ビュープロピオンの薬学的使用 |
| 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 |
| US6933289B2 (en) | 2003-07-01 | 2005-08-23 | Allergan, Inc. | Inhibition of irritating side effects associated with use of a topical ophthalmic medication |
| US8512717B2 (en) | 2003-08-07 | 2013-08-20 | Allergan, Inc. | Compositions for delivery of therapeutics into the eyes and methods for making and using same |
| 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 |
| WO2005113798A2 (en) | 2004-04-15 | 2005-12-01 | University Of Florida Research Foundation, Inc. | Proteolytic markers as diagnostic biomarkers for cancer, organ injury and muscle rehabilitation/exercise overtraining |
| WO2011143160A2 (en) | 2010-05-10 | 2011-11-17 | The Johns Hopkins University | Metabolic inhibitor against tumors having an idh mutation |
| US20110281234A1 (en) | 2010-05-12 | 2011-11-17 | Colton Crane | System and methods for removing a loose tooth |
| WO2012006506A1 (en) | 2010-07-09 | 2012-01-12 | Massachusetts Institute Of Technology | Metabolic gene, enzyme, and flux targets for cancer therapy |
| 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 |
| RS59705B1 (sr) * | 2011-11-21 | 2020-01-31 | Calithera Biosciences Inc | Heterociklični inhibitori glutaminaze |
| US8604016B2 (en) | 2011-11-21 | 2013-12-10 | Calithera Biosciences Inc. | Heterocyclic inhibitors of glutaminase |
| JP6275153B2 (ja) | 2012-11-16 | 2018-02-07 | 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 | ヘテロ環式グルタミナーゼ阻害剤 |
| MX369691B (es) | 2012-11-21 | 2019-11-19 | Agios Pharmaceuticals Inc | Inhibidores de glutaminasa y métodos de empleo. |
| 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 |
| CA2892817A1 (en) | 2012-12-03 | 2014-06-12 | Calithera Biosciences Inc. | Treatment of cancer with heterocyclic inhibitors of glutaminase |
| 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 |
| AU2015274361B2 (en) | 2014-06-13 | 2020-11-05 | Calithera Biosciences, Inc. | Combination therapy with glutaminase inhibitors |
| EA037738B1 (ru) | 2014-08-07 | 2021-05-17 | Калитера Байосайенсиз, Инк. | Кристаллические формы ингибиторов глутаминазы |
| JP6768693B2 (ja) | 2015-03-30 | 2020-10-14 | 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を投与する方法 |
| US10441587B2 (en) | 2015-04-06 | 2019-10-15 | Calithera Biosciences, Inc. | Treatment of lung cancer with inhibitors of glutaminase |
| WO2017062354A1 (en) | 2015-10-05 | 2017-04-13 | Calithera Biosciences, Inc. | Combination therapy with glutaminase inhibitors and immuno-oncology agents |
| WO2018039544A1 (en) | 2016-08-25 | 2018-03-01 | Calithera Biosciences, Inc. | Combination therapy with glutaminase inhibitors |
| JP2020510032A (ja) | 2017-03-10 | 2020-04-02 | 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の併用療法 |
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2013
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- 2013-11-15 CN CN201380069950.3A patent/CN105051041B/zh active Active
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- 2013-11-15 SM SM20210589T patent/SMT202100589T1/it unknown
- 2013-11-15 ES ES13855039T patent/ES2899461T3/es active Active
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- 2013-11-15 DK DK13855039.7T patent/DK2920168T3/da active
- 2013-11-15 HU HUE13855039A patent/HUE056078T2/hu unknown
- 2013-11-15 RS RS20211273A patent/RS62447B1/sr unknown
- 2013-11-15 PL PL13855039T patent/PL2920168T3/pl unknown
- 2013-11-15 EA EA201590941A patent/EA029707B1/ru not_active IP Right Cessation
- 2013-11-15 WO PCT/US2013/070277 patent/WO2014078645A1/en not_active Ceased
- 2013-11-15 KR KR1020157015874A patent/KR102220175B1/ko active Active
- 2013-11-15 HR HRP20211610TT patent/HRP20211610T1/hr unknown
- 2013-11-15 MX MX2015005963A patent/MX381260B/es unknown
- 2013-11-15 PT PT138550397T patent/PT2920168T/pt unknown
- 2013-11-15 US US14/081,175 patent/US10793535B2/en active Active
- 2013-11-15 SG SG11201503720SA patent/SG11201503720SA/en unknown
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2015
- 2015-05-13 IL IL238787A patent/IL238787A0/en unknown
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2016
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2020
- 2020-10-05 US US17/063,066 patent/US20210292289A1/en not_active Abandoned
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2021
- 2021-10-19 CY CY20211100905T patent/CY1125279T1/el unknown
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