CN115109075B - 突变体idh1和idh2抑制剂 - Google Patents
突变体idh1和idh2抑制剂 Download PDFInfo
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- CN115109075B CN115109075B CN202210758386.7A CN202210758386A CN115109075B CN 115109075 B CN115109075 B CN 115109075B CN 202210758386 A CN202210758386 A CN 202210758386A CN 115109075 B CN115109075 B CN 115109075B
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- Prior art keywords
- ethyl
- phenyl
- compound
- oxazin
- amino
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- 101001042041 Bos taurus Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial Proteins 0.000 title claims abstract description 71
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- 101000599886 Homo sapiens Isocitrate dehydrogenase [NADP], mitochondrial Proteins 0.000 title claims abstract description 43
- 102100037845 Isocitrate dehydrogenase [NADP], mitochondrial Human genes 0.000 title claims abstract description 43
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- USFRTQXJZLVVJL-UHFFFAOYSA-N 7-(2-phenylethylamino)-1,4-dihydropyrimido[4,5-d][1,3]oxazin-2-one Chemical class C1(=CC=CC=C1)CCNC=1N=CC2=C(NC(OC2)=O)N=1 USFRTQXJZLVVJL-UHFFFAOYSA-N 0.000 abstract 1
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- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- CTCGRXDGXGUOTE-UHFFFAOYSA-N tert-butyl 2-ethylpiperazine-1-carboxylate Chemical compound CCC1CNCCN1C(=O)OC(C)(C)C CTCGRXDGXGUOTE-UHFFFAOYSA-N 0.000 description 1
- YWMLDYIVAGDULB-NBGIEHNGSA-N tert-butyl 4-[(1R)-2-cyclopropyl-1-[4-[(1S)-1-[(1-ethyl-2-oxo-4H-pyrimido[4,5-d][1,3]oxazin-7-yl)amino]ethyl]phenyl]ethyl]piperazine-1-carboxylate Chemical compound CCN1C(=O)OCc2cnc(N[C@@H](C)c3ccc(cc3)[C@@H](CC3CC3)N3CCN(CC3)C(=O)OC(C)(C)C)nc12 YWMLDYIVAGDULB-NBGIEHNGSA-N 0.000 description 1
- XDHUYSHWCCPDKR-DIMJTDRSSA-N tert-butyl 4-[1-[4-[(1S)-1-aminoethyl]phenyl]-3-methylbutyl]piperazine-1-carboxylate Chemical compound CC(C)CC(N1CCN(CC1)C(=O)OC(C)(C)C)c1ccc(cc1)[C@H](C)N XDHUYSHWCCPDKR-DIMJTDRSSA-N 0.000 description 1
- JUHDQPLVTZBONJ-DQUNLGLBSA-N tert-butyl 4-[2-cyclopropyl-1-[4-[(1S)-1-[(1-methyl-2-oxo-4H-pyrido[4,3-d][1,3]oxazin-7-yl)amino]ethyl]phenyl]ethyl]piperazine-1-carboxylate Chemical compound C1(CC1)CC(C1=CC=C(C=C1)[C@H](C)NC1=CC=2N(C(OCC=2C=N1)=O)C)N1CCN(CC1)C(=O)OC(C)(C)C JUHDQPLVTZBONJ-DQUNLGLBSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003628 tricarboxylic acids Chemical class 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
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- 210000004881 tumor cell Anatomy 0.000 description 1
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- 238000003828 vacuum filtration Methods 0.000 description 1
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Classifications
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- 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
- A61K31/535—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
- A61K31/5365—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 ortho- or peri-condensed with heterocyclic ring systems
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210758386.7A CN115109075B (zh) | 2016-12-16 | 2017-12-08 | 突变体idh1和idh2抑制剂 |
Applications Claiming Priority (5)
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|---|---|---|---|
| US201662435283P | 2016-12-16 | 2016-12-16 | |
| US62/435283 | 2016-12-16 | ||
| CN202210758386.7A CN115109075B (zh) | 2016-12-16 | 2017-12-08 | 突变体idh1和idh2抑制剂 |
| PCT/US2017/065246 WO2018111707A1 (en) | 2016-12-16 | 2017-12-08 | 7-phenylethylamino-4h-pyrimido[4,5-d][1,3]oxazin-2-one compounds as mutant idh1 and idh2 inhibitors |
| CN201780078017.0A CN110072867B (zh) | 2016-12-16 | 2017-12-08 | 作为突变体idh1和idh2抑制剂的7-苯基乙基氨基-4h-嘧啶并[4,5-d][1,3]噁嗪-2-酮化合物 |
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| CN201780078017.0A Division CN110072867B (zh) | 2016-12-16 | 2017-12-08 | 作为突变体idh1和idh2抑制剂的7-苯基乙基氨基-4h-嘧啶并[4,5-d][1,3]噁嗪-2-酮化合物 |
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| CN115109075A CN115109075A (zh) | 2022-09-27 |
| CN115109075B true CN115109075B (zh) | 2024-09-20 |
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| CN202210758386.7A Active CN115109075B (zh) | 2016-12-16 | 2017-12-08 | 突变体idh1和idh2抑制剂 |
| CN201780078017.0A Active CN110072867B (zh) | 2016-12-16 | 2017-12-08 | 作为突变体idh1和idh2抑制剂的7-苯基乙基氨基-4h-嘧啶并[4,5-d][1,3]噁嗪-2-酮化合物 |
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| CN201780078017.0A Active CN110072867B (zh) | 2016-12-16 | 2017-12-08 | 作为突变体idh1和idh2抑制剂的7-苯基乙基氨基-4h-嘧啶并[4,5-d][1,3]噁嗪-2-酮化合物 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP3194383B1 (en) | 2014-09-19 | 2019-11-06 | Forma Therapeutics, Inc. | Quinolinone pyrimidines compositions as mutant-isocitrate dehydrogenase inhibitors |
| MA53352A (fr) | 2014-09-19 | 2021-09-15 | Forma Therapeutics Inc | Dérivés de pyridin-2-(1h)-one-quinolinone en tant qu'inhibiteurs d'isocitrate déshydrogénase |
| MX372964B (es) | 2014-09-19 | 2020-03-27 | Forma Therapeutics Inc | Derivados de fenil quinolinona como inhibidores de isocitrato deshidrogenasa mutante (mt-idh) |
| AU2015317327B9 (en) | 2014-09-19 | 2020-04-09 | Forma Therapeutics, Inc. | Pyridinyl quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors |
| US9624175B2 (en) | 2015-04-21 | 2017-04-18 | Forma Therapeutics, Inc. | Fused-bicyclic aryl quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors |
| US10407419B2 (en) | 2015-04-21 | 2019-09-10 | Forma Therapeutics, Inc. | Quinolinone five-membered heterocyclic compounds as mutant-isocitrate dehydrogenase inhibitors |
| EP3640251B1 (en) | 2016-10-24 | 2021-12-08 | Astrazeneca AB | 6,7,8,9-tetrahydro-3h-pyrazolo[4,3-f]isoquinoline derivatives useful in the treatment of cancer |
| JP7291077B2 (ja) | 2016-12-16 | 2023-06-14 | ヤンセン ファーマシューティカ エヌ．ベー． | Ｊａｋファミリーのキナーゼの低分子阻害物質 |
| ES2941631T3 (es) * | 2016-12-16 | 2023-05-24 | Lilly Co Eli | Compuestos de Pirido[4,3-d][1,3]oxazin-2-ona como inhibidores de IDH1 e IDH2 mutantes |
| JOP20190144A1 (ar) | 2016-12-16 | 2019-06-16 | Janssen Pharmaceutica Nv | إيميدازو بيرولو بيريدين كمثبطات لعائلة jak الخاصة بإنزيمات الكيناز |
| PL3494116T3 (pl) | 2017-01-30 | 2020-04-30 | Astrazeneca Ab | Modulatory receptora estrogenowego |
| US11013734B2 (en) | 2018-05-16 | 2021-05-25 | Forma Therapeutics, Inc. | Treating patients harboring an isocitrate dehydrogenase-1 (IDH-1) mutation |
| US20210196701A1 (en) | 2018-05-16 | 2021-07-01 | Forma Therapeutics, Inc. | Inhibiting mutant idh-1 |
| WO2019222551A1 (en) | 2018-05-16 | 2019-11-21 | Forma Therapeutics, Inc. | Solid forms of ((s)-5-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile |
| US11013733B2 (en) | 2018-05-16 | 2021-05-25 | Forma Therapeutics, Inc. | Inhibiting mutant isocitrate dehydrogenase 1 (mlDH-1) |
| US11311527B2 (en) | 2018-05-16 | 2022-04-26 | Forma Therapeutics, Inc. | Inhibiting mutant isocitrate dehydrogenase 1 (mIDH-1) |
| TW202016110A (zh) | 2018-06-15 | 2020-05-01 | 比利時商健生藥品公司 | Ｊａｋ激酶家族之小分子抑制劑 |
| CN115038700B (zh) * | 2019-11-08 | 2025-07-25 | 内尔维亚诺医疗科学公司 | 偕二取代的杂环化合物及其作为idh抑制剂的用途 |
| MX2022011846A (es) * | 2020-03-23 | 2023-01-04 | Lilly Co Eli | Metodo para el tratamiento de sujetos resistentes al inhibidor idh1. |
| CN115443137B (zh) * | 2020-03-23 | 2024-05-31 | 伊莱利利公司 | 使用突变idh抑制剂和bcl-2抑制剂的组合疗法 |
| AU2021242260B2 (en) * | 2020-03-23 | 2023-12-14 | Eli Lilly And Company | Combination therapy with a mutant IDH inhibitor |
| MX2022013258A (es) | 2020-04-24 | 2022-11-14 | Astrazeneca Ab | Formulaciones farmaceuticas. |
| MX2022013391A (es) | 2020-04-24 | 2022-11-30 | Astrazeneca Ab | Pauta posologica para el tratamiento del cancer. |
| US12559505B2 (en) | 2020-06-28 | 2026-02-24 | Wigen Biomedicine Technology (shanghai) Co., Ltd. | IDH mutant inhibitor and use thereof |
| WO2022020281A1 (en) | 2020-07-20 | 2022-01-27 | Eli Lilly And Company | Combination therapy with a mutant idh1 inhibitor, a deoxyadenosine analog, and a platinum agent |
| MX2023010642A (es) | 2021-03-11 | 2023-11-28 | Janssen Pharmaceutica Nv | Lorpucitinib para uso en el tratamiento de trastornos mediados por jak. |
| CN113588768B (zh) * | 2021-05-18 | 2022-07-05 | 国家卫生健康委科学技术研究所 | 一种以分子图像方式定量组织内内源性代谢物的质谱方法 |
| US20240261294A1 (en) * | 2021-06-09 | 2024-08-08 | Eli Lilly And Company | Method for treating idh inhibitor-resistant subjects |
| CA3217608A1 (en) | 2021-06-15 | 2022-12-22 | Yuli Xie | Idh mutant inhibitor and use thereof |
| US11746115B2 (en) | 2021-08-13 | 2023-09-05 | Eli Lilly And Company | Solid forms of 7-[[(1S)-1-[4-[(1S)-2-cyclopropyl-1-(4-prop-2-enoylpiperazin-1-yl)ethyl]phenyl]ethyl]amino]-1-ethyl-4H-pyrimido[4,5-d][1,3]oxazin-2-one |
| WO2023141087A1 (en) | 2022-01-19 | 2023-07-27 | Eli Lilly And Company | Combination therapy with a mutant idh inhibitor |
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| WO2017019429A1 (en) * | 2015-07-27 | 2017-02-02 | Eli Lilly And Company | 7-phenylethylamino-4h-pyrimido[4,5-d][1,3]oxazin-2-one compounds and theit use as mutant idh1 inhibitors |
| CN110072867B (zh) * | 2016-12-16 | 2022-07-08 | 伊莱利利公司 | 作为突变体idh1和idh2抑制剂的7-苯基乙基氨基-4h-嘧啶并[4,5-d][1,3]噁嗪-2-酮化合物 |
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| BR112014007310A2 (pt) * | 2011-09-27 | 2017-04-04 | Novartis Ag | 3-pirimidin-4-il-oxazolidin-2-onas como inibidores de idh mutante |
| AU2014229283B2 (en) * | 2013-03-14 | 2016-07-28 | Novartis Ag | 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant IDH |
| WO2014147586A1 (en) * | 2013-03-22 | 2014-09-25 | Novartis Ag | 1-(2-(ethylamino)pyrimidin-4-yl)pyrrolidin-2-ones as inhibitors of mutant idh |
| US9624175B2 (en) * | 2015-04-21 | 2017-04-18 | Forma Therapeutics, Inc. | Fused-bicyclic aryl quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors |
| CN107405687A (zh) * | 2015-04-24 | 2017-11-28 | 哈利伯顿能源服务公司 | 制作陶瓷或金属间化合物零件的方法 |
| CN109311863B (zh) * | 2016-06-06 | 2021-10-29 | 伊莱利利公司 | 突变型idh1抑制剂 |
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Patent Citations (2)
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| WO2017019429A1 (en) * | 2015-07-27 | 2017-02-02 | Eli Lilly And Company | 7-phenylethylamino-4h-pyrimido[4,5-d][1,3]oxazin-2-one compounds and theit use as mutant idh1 inhibitors |
| CN110072867B (zh) * | 2016-12-16 | 2022-07-08 | 伊莱利利公司 | 作为突变体idh1和idh2抑制剂的7-苯基乙基氨基-4h-嘧啶并[4,5-d][1,3]噁嗪-2-酮化合物 |
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