UA114414C2 - Введення інгібітору ферменту, що активує nedd8, і гіпометилуючого засобу - Google Patents
Введення інгібітору ферменту, що активує nedd8, і гіпометилуючого засобу Download PDFInfo
- Publication number
- UA114414C2 UA114414C2 UAA201405842A UAA201405842A UA114414C2 UA 114414 C2 UA114414 C2 UA 114414C2 UA A201405842 A UAA201405842 A UA A201405842A UA A201405842 A UAA201405842 A UA A201405842A UA 114414 C2 UA114414 C2 UA 114414C2
- Authority
- UA
- Ukraine
- Prior art keywords
- pharmaceutically acceptable
- acceptable salt
- inden
- dihydro
- administered
- Prior art date
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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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
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Landscapes
- Health & Medical Sciences (AREA)
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- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161555049P | 2011-11-03 | 2011-11-03 | |
| PCT/US2012/063382 WO2013067396A2 (en) | 2011-11-03 | 2012-11-02 | Administration of nedd8-activating enzyme inhibitor and hypomethylating agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA114414C2 true UA114414C2 (uk) | 2017-06-12 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UAA201405842A UA114414C2 (uk) | 2011-11-03 | 2012-11-02 | Введення інгібітору ферменту, що активує nedd8, і гіпометилуючого засобу |
Country Status (23)
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|---|---|
| US (2) | US8980850B2 (https=) |
| EP (1) | EP2773360B1 (https=) |
| JP (2) | JP6231988B2 (https=) |
| KR (1) | KR101987861B1 (https=) |
| CN (1) | CN104245699B (https=) |
| AU (1) | AU2012321106C1 (https=) |
| BR (1) | BR112014010699B1 (https=) |
| CA (1) | CA2854461C (https=) |
| EA (1) | EA028380B1 (https=) |
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Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2430026A1 (en) | 2009-05-14 | 2012-03-21 | Millennium Pharmaceuticals, Inc. | Hydrochloride salt of ((1s,2s,4r)-4-{4-[(1s)-2,3-dihydro-1h-inden-1-ylamino]-7h-pyrrolo [2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate |
| JP6038150B2 (ja) * | 2011-08-24 | 2016-12-07 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | Ｎｅｄｄ８活性化酵素阻害剤 |
| EP2764866A1 (en) * | 2013-02-07 | 2014-08-13 | IP Gesellschaft für Management mbH | Inhibitors of nedd8-activating enzyme |
| CA2923752A1 (en) | 2013-05-14 | 2014-11-20 | Millennium Pharmaceuticals, Inc. | Administration of nedd8-activating enzyme inhibitor and chemotherapeutic agents |
| JP2016525531A (ja) * | 2013-07-26 | 2016-08-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 急性骨髄性白血病及び骨髄異形成症候群の処置のためのアザシチジンと組み合わせたボラセルチブ |
| KR102359214B1 (ko) | 2014-04-04 | 2022-02-07 | 델 마 파마슈티컬스 | 폐의 비소세포 암종 및 난소암을 치료하기 위한 디안하이드로갈락티톨 및 이의 유사체 또는 유도체 |
| CN103948590A (zh) * | 2014-05-22 | 2014-07-30 | 中国药科大学 | Nedd8激活酶抑制剂及其医药用途 |
| US10695352B2 (en) * | 2015-10-15 | 2020-06-30 | Celgene Corporation | Combination therapy for treating malignancies |
| WO2018218119A1 (en) * | 2017-05-25 | 2018-11-29 | The Board Of Trustees Of The Leland Stanford Junior University | Combination of low dose il-2 and an inhibitor of treg il-2r desensitization to treat autoimmune and allergic inflammatory diseases |
| EP3684363A4 (en) * | 2017-09-21 | 2021-05-12 | Millennium Pharmaceuticals, Inc. | CO-CRYSTALLINE FORMS OF ((1S, 2S, 4R) -4- {4 - [(1S) -2,3-DIHYDRO-1H-INDÉN-1-YLAMINO] -7H-PYRROLO [2,3-D] PYRIMIDIN -7-YL} -2-HYDROXYCYCLOPENTYL) METHYLSULFAMATE, THEIR FORMULATIONS AND USES |
| US20220017908A1 (en) * | 2018-11-20 | 2022-01-20 | Fulcrum Therapeutics, Inc. | Compositions and methods for increasing fetal hemoglobin and treating sickle cell disease |
| CA3133751A1 (en) | 2019-03-15 | 2020-09-24 | Fulcrum Therapeutics, Inc. | Macrocyclic azolopyridine derivatives as eed and prc2 modulators |
| WO2023025668A1 (en) | 2021-08-25 | 2023-03-02 | Asociación Centro De Investigación Cooperativa En Biociencias-Cic Biogune | Methods for the generation of stem cell memory t cells for adoptive t cell therapy |
| WO2023242235A1 (en) * | 2022-06-14 | 2023-12-21 | Scandion Oncology A/S | Abcg2 inhibitor and nae inhibitor for the treatment of cancer |
| CN115007323B (zh) * | 2022-06-17 | 2024-01-23 | 中南大学 | 一种抑制矿物中黄铁矿浮选的方法 |
| EP4554608A1 (en) * | 2022-07-11 | 2025-05-21 | Westlake University | Use of a fbxo42 specific inhibitor in treating notch signaling-dependent disease |
Family Cites Families (16)
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| US6887855B2 (en) | 2003-03-17 | 2005-05-03 | Pharmion Corporation | Forms of 5-azacytidine |
| US6943249B2 (en) | 2003-03-17 | 2005-09-13 | Ash Stevens, Inc. | Methods for isolating crystalline Form I of 5-azacytidine |
| US20060063735A1 (en) | 2004-09-17 | 2006-03-23 | Supergen, Inc. | Salts of 5-azacytidine |
| US20060128654A1 (en) | 2004-12-10 | 2006-06-15 | Chunlin Tang | Pharmaceutical formulation of cytidine analogs and derivatives |
| RS52458B (sr) | 2005-02-04 | 2013-02-28 | Millennium Pharmaceuticals Inc. | Inhibitori e1 aktivirajućih enzima |
| EA024006B1 (ru) | 2006-02-02 | 2016-08-31 | Миллениум Фармасьютикалз, Инк. | Ингибиторы е1 активирующих ферментов |
| ZA200900670B (en) * | 2006-08-08 | 2010-04-28 | Millennium Pharm Inc | Heteroaryl compounds useful as inhititors of E1 activating enzymes |
| US20080057086A1 (en) | 2006-09-01 | 2008-03-06 | Pharmion Corporation | Colon-targeted oral formulations of cytidine analogs |
| EP2211870A1 (en) | 2007-11-01 | 2010-08-04 | Celgene Corporation | Cytidine analogs for treatment of myelodysplastic syndromes |
| EP2257310A2 (en) * | 2008-02-26 | 2010-12-08 | Nerviano Medical Sciences S.r.l. | Antitumor combination comprising a morpholinyl anthracycline derivative and demethylating agents |
| EP3782612B1 (en) | 2008-05-15 | 2023-11-08 | Celgene Corporation | Oral formulations of cytidine analogs and methods of use thereof |
| NZ589719A (en) * | 2008-06-09 | 2012-08-31 | Cyclacel Ltd | Combinations of sapacitabine or cndac with dna methyltransferase inhibitors such as decitabine and procaine |
| CN102438588B (zh) * | 2009-03-23 | 2015-04-01 | 埃姆比特生物科学公司 | 使用联合治疗法治疗疾病的方法 |
| EP2430026A1 (en) | 2009-05-14 | 2012-03-21 | Millennium Pharmaceuticals, Inc. | Hydrochloride salt of ((1s,2s,4r)-4-{4-[(1s)-2,3-dihydro-1h-inden-1-ylamino]-7h-pyrrolo [2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate |
| WO2012106299A1 (en) | 2011-01-31 | 2012-08-09 | Celgene Corporation | Pharmaceutical compositions of cytidine analogs and methods of use thereof |
| US9125884B2 (en) | 2011-11-01 | 2015-09-08 | Celgene Corporation | Methods for treating cancers using oral formulations of cytidine analogs |
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- 2012-11-02 JP JP2014540146A patent/JP6231988B2/ja active Active
- 2012-11-02 HK HK15102294.2A patent/HK1201733A1/xx unknown
- 2012-11-02 ES ES12844799.2T patent/ES2668272T3/es active Active
- 2012-11-02 MX MX2014005323A patent/MX357835B/es active IP Right Grant
- 2012-11-02 TR TR2018/07342T patent/TR201807342T4/tr unknown
- 2012-11-02 WO PCT/US2012/063382 patent/WO2013067396A2/en not_active Ceased
- 2012-11-02 CN CN201280062112.9A patent/CN104245699B/zh active Active
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- 2012-11-02 CA CA2854461A patent/CA2854461C/en not_active Expired - Fee Related
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2014
- 2014-04-29 IL IL232353A patent/IL232353B/en active IP Right Grant
- 2014-04-30 TN TNP2014000194A patent/TN2014000194A1/en unknown
- 2014-05-26 MA MA37066A patent/MA35662B1/fr unknown
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