AU2012236476A1 - Systhesis of 5-azacytidine - Google Patents
Systhesis of 5-azacytidine Download PDFInfo
- Publication number
- AU2012236476A1 AU2012236476A1 AU2012236476A AU2012236476A AU2012236476A1 AU 2012236476 A1 AU2012236476 A1 AU 2012236476A1 AU 2012236476 A AU2012236476 A AU 2012236476A AU 2012236476 A AU2012236476 A AU 2012236476A AU 2012236476 A1 AU2012236476 A1 AU 2012236476A1
- Authority
- AU
- Australia
- Prior art keywords
- azacytidine
- salt
- less
- reaction
- yield
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 title claims abstract description 422
- 229960002756 azacitidine Drugs 0.000 title claims abstract description 409
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 title claims abstract description 406
- 238000000034 method Methods 0.000 claims abstract description 101
- 230000008569 process Effects 0.000 claims abstract description 82
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 274
- 150000003839 salts Chemical class 0.000 claims description 228
- 238000006243 chemical reaction Methods 0.000 claims description 178
- MFEFTTYGMZOIKO-UHFFFAOYSA-N 5-azacytosine Chemical compound NC1=NC=NC(=O)N1 MFEFTTYGMZOIKO-UHFFFAOYSA-N 0.000 claims description 97
- 239000000203 mixture Substances 0.000 claims description 93
- 150000001875 compounds Chemical class 0.000 claims description 89
- 239000003153 chemical reaction reagent Substances 0.000 claims description 73
- 239000012458 free base Substances 0.000 claims description 73
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 72
- 239000012453 solvate Substances 0.000 claims description 72
- 239000002841 Lewis acid Substances 0.000 claims description 70
- 150000007517 lewis acids Chemical class 0.000 claims description 70
- 239000012535 impurity Substances 0.000 claims description 67
- 238000005859 coupling reaction Methods 0.000 claims description 64
- 239000002904 solvent Substances 0.000 claims description 58
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 55
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 52
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 claims description 50
- 239000003960 organic solvent Substances 0.000 claims description 46
- 239000002585 base Substances 0.000 claims description 42
- 229910052751 metal Inorganic materials 0.000 claims description 41
- 239000002184 metal Substances 0.000 claims description 41
- QCSYIPZVPFBDLC-MVNLRXSJSA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one;hydrochloride Chemical compound Cl.O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 QCSYIPZVPFBDLC-MVNLRXSJSA-N 0.000 claims description 39
- 239000002253 acid Substances 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 125000003118 aryl group Chemical group 0.000 claims description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 38
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims description 37
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims description 37
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 36
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 33
- 230000003472 neutralizing effect Effects 0.000 claims description 30
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 28
- 238000001914 filtration Methods 0.000 claims description 26
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 25
- 125000002252 acyl group Chemical group 0.000 claims description 23
- 238000006884 silylation reaction Methods 0.000 claims description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 239000012296 anti-solvent Substances 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 14
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical group [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 12
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- 230000000171 quenching effect Effects 0.000 claims description 12
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 11
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- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 9
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 9
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 9
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 8
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- 239000000908 ammonium hydroxide Substances 0.000 claims description 6
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 3
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 38
- 201000003793 Myelodysplastic syndrome Diseases 0.000 abstract description 33
- 238000002360 preparation method Methods 0.000 abstract description 25
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- 208000014951 hematologic disease Diseases 0.000 abstract description 4
- -1 AZA Chemical compound 0.000 description 103
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 51
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- 238000000634 powder X-ray diffraction Methods 0.000 description 35
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 32
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- 238000001953 recrystallisation Methods 0.000 description 21
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- 125000004432 carbon atom Chemical group C* 0.000 description 18
- 239000012299 nitrogen atmosphere Substances 0.000 description 18
- 239000004215 Carbon black (E152) Substances 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
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- 239000007858 starting material Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 125000001072 heteroaryl group Chemical group 0.000 description 15
- 229910052742 iron Inorganic materials 0.000 description 15
- 125000001424 substituent group Chemical group 0.000 description 15
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 14
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- 125000000623 heterocyclic group Chemical group 0.000 description 14
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- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 13
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- 239000003814 drug Substances 0.000 description 13
- 238000002329 infrared spectrum Methods 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
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- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- OTQJVHISAFFLMA-DDHJBXDOSA-N [(2r,3r,4r,5r)-3,4-diacetyloxy-5-(4-amino-2-oxo-1,3,5-triazin-1-yl)oxolan-2-yl]methyl acetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1N1C(=O)N=C(N)N=C1 OTQJVHISAFFLMA-DDHJBXDOSA-N 0.000 description 12
- 125000000304 alkynyl group Chemical group 0.000 description 12
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
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- ZBFWTQVVDWBGGY-MVNLRXSJSA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one;hydrobromide Chemical compound Br.O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZBFWTQVVDWBGGY-MVNLRXSJSA-N 0.000 description 10
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- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 9
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- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/12—Triazine radicals
-
- 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
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161470392P | 2011-03-31 | 2011-03-31 | |
| US61/470,392 | 2011-03-31 | ||
| PCT/US2012/031059 WO2012135405A1 (en) | 2011-03-31 | 2012-03-29 | Systhesis of 5-azacytidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2012236476A1 true AU2012236476A1 (en) | 2013-05-02 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2012236476A Abandoned AU2012236476A1 (en) | 2011-03-31 | 2012-03-29 | Systhesis of 5-azacytidine |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US9951098B2 (enExample) |
| EP (1) | EP2691408B1 (enExample) |
| JP (1) | JP6289361B2 (enExample) |
| KR (1) | KR20140019820A (enExample) |
| CN (1) | CN103619864A (enExample) |
| AU (1) | AU2012236476A1 (enExample) |
| BR (1) | BR112013025167A2 (enExample) |
| IL (1) | IL228604A0 (enExample) |
| MX (1) | MX2013010945A (enExample) |
| RU (1) | RU2013148580A (enExample) |
| SG (1) | SG193622A1 (enExample) |
| WO (1) | WO2012135405A1 (enExample) |
| ZA (1) | ZA201307142B (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT2695609T (pt) | 2008-05-15 | 2020-03-02 | Celgene Corp | Formulações orais de análogos da citidina e métodos de utilização dos mesmos |
| CA2825152A1 (en) | 2011-01-31 | 2012-08-09 | Celgene Corporation | Pharmaceutical compositions of cytidine analogs and methods of use thereof |
| WO2014160698A1 (en) * | 2013-03-26 | 2014-10-02 | Celgene Corporation | SOLID FORMS COMPRISING 4-AMINO-I-β-D-RIBOFURANOSYL-1,3,5-TRIAZIN-2(1H)-ONE AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF |
| US10221216B2 (en) | 2013-04-11 | 2019-03-05 | Carnegie Mellon University | Template-directed γPNA synthesis process and γPNA targeting compounds |
| WO2014169206A2 (en) | 2013-04-11 | 2014-10-16 | Carnegie Mellon University | Divalent nucleobase compounds and uses therefor |
| CN103450303A (zh) * | 2013-09-04 | 2013-12-18 | 重庆泰濠制药有限公司 | 阿扎胞苷晶型a、阿扎胞苷晶型b及其制备方法 |
| CN104672289A (zh) * | 2013-11-29 | 2015-06-03 | 南京圣和药业股份有限公司 | 一种阿扎胞苷杂质的制备方法 |
| WO2017183215A1 (ja) * | 2016-04-21 | 2017-10-26 | 大原薬品工業株式会社 | ５－アザシチジン類の糖部シリルエーテル誘導体 |
| CN109923105A (zh) | 2016-09-26 | 2019-06-21 | 卡耐基梅隆大学 | 二价核碱基化合物及其用途 |
| CN109305992A (zh) * | 2017-07-28 | 2019-02-05 | 江苏先声药业有限公司 | 一种阿扎胞苷的制备方法 |
| CN109988207B (zh) * | 2017-12-29 | 2022-01-04 | 江苏豪森药业集团有限公司 | 阿扎胞苷晶型的制备方法 |
| CN110092807A (zh) * | 2018-01-30 | 2019-08-06 | 中国医学科学院药物研究所 | 一种高纯、低灼烧残渣的制备阿扎胞苷的方法 |
| CA3211506A1 (en) | 2018-02-07 | 2019-08-15 | Lovelace Biomedical Research Institute | Inhalable dry powder cytidine analogue composition and method of use as a treatment for cancer |
| KR20190136284A (ko) * | 2018-05-30 | 2019-12-10 | 주식회사 삼양바이오팜 | 안정한 아자시티딘-함유 약제학적 조성물의 제조방법 |
| WO2022113069A1 (en) | 2020-11-24 | 2022-06-02 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | E protein channel blockers and orf3 inhibitors as anti-covid-19 agents |
| KR20230035524A (ko) | 2020-05-01 | 2023-03-14 | 이슘 리서치 디벨롭먼트 컴퍼니 오브 더 히브루 유니버시티 오브 예루살렘 엘티디. | Covid-19 치료제로서 e 단백질 채널 차단제 및 orf3 억제제 |
| CN113201039B (zh) * | 2021-05-19 | 2022-04-29 | 南京德克瑞医药化工有限公司 | 一种医药中间体2’,3’,5’-三乙酰阿扎胞苷的制备方法 |
| US20250195653A1 (en) | 2023-11-28 | 2025-06-19 | Sanofi | Multifunctional natural killer (nk) cell engager combination therapy for treating hematological neoplastic disorders |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
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| GB1050899A (enExample) | 1963-12-22 | |||
| CH527207A (de) | 1968-05-08 | 1972-08-31 | Ceskoslovenska Akademie Ved | Verfahren zur Herstellung von 1-Glycosyl-5-azacytosinen |
| CH507969A (de) | 1968-11-12 | 1971-05-31 | Ceskoslovenska Akademie Ved | Verfahren zur Herstellung von 1-Glycosyl-5-azacytosinen |
| DE2012888C3 (de) | 1970-03-14 | 1981-04-02 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur Herstellung von 5-Azapyrimidinnucleosiden |
| FR2123632A6 (en) | 1971-01-26 | 1972-09-15 | Ceskoslovenska Akademie Ved | Prepn of 5-azacytosines and 5-azacytidines - from bis trimethylsilyl-5-azacytosine |
| DE2122991C2 (de) | 1971-05-04 | 1982-06-09 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur Herstellung von Cytosin- und 6-Azacytosinnucleosiden |
| DE2508312A1 (de) | 1975-02-24 | 1976-09-02 | Schering Ag | Neues verfahren zur herstellung von nucleosiden |
| DE2757365A1 (de) | 1977-12-20 | 1979-06-21 | Schering Ag | Neues verfahren zur herstellung von nucleosiden |
| CZ120699A3 (cs) * | 1996-10-16 | 1999-09-15 | Icn Pharmaceuticals, Inc. | Monocyklická L-nukleosidová analoga a jejich využití |
| EP1545558A4 (en) | 2002-09-24 | 2010-02-17 | Koronis Pharmaceuticals Inc | 1, 3, 5-TRIAZINES FOR THE TREATMENT OF VIRAL DISEASES |
| US7189740B2 (en) | 2002-10-15 | 2007-03-13 | Celgene Corporation | Methods of using 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myelodysplastic syndromes |
| US7038038B2 (en) | 2003-03-17 | 2006-05-02 | Pharmion Corporation | Synthesis of 5-azacytidine |
| 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 |
| CN101856348A (zh) | 2003-08-29 | 2010-10-13 | 斯隆-凯特林癌症研究所 | 联合治疗癌症的方法 |
| US7192781B2 (en) | 2004-04-13 | 2007-03-20 | Pharmion Corporation | Methods for stabilizing 5-azacytidine in plasma |
| US20060063735A1 (en) | 2004-09-17 | 2006-03-23 | Supergen, Inc. | Salts of 5-azacytidine |
| US20060069060A1 (en) | 2004-09-27 | 2006-03-30 | Sanjeev Redkar | Salts of decitabine |
| WO2008028193A2 (en) | 2006-09-01 | 2008-03-06 | Pharmion Corporation | Colon-targeted oral formulations of cytidine analogs |
| EP2118117A2 (en) | 2007-01-11 | 2009-11-18 | IVAX Pharmaceuticals s.r.o. | Solid state forms of 5-azacytidine and processes for preparation thereof |
| US20110288042A1 (en) | 2007-08-02 | 2011-11-24 | Chemagis Ltd. | Stable highly pure azacitidine and preparation methods therefor |
| EP2048151A1 (en) | 2007-10-10 | 2009-04-15 | Cilag AG | Method for producing nucleosides by direct glycosylation of the nucleoside base |
| JP2011505336A (ja) | 2007-11-01 | 2011-02-24 | セルジーン コーポレイション | 骨髄異形成症候群治療のためのシチジンアナログ |
| PT2695609T (pt) | 2008-05-15 | 2020-03-02 | Celgene Corp | Formulações orais de análogos da citidina e métodos de utilização dos mesmos |
| WO2010014883A2 (en) | 2008-08-01 | 2010-02-04 | Dr. Reddy's Laboratories Ltd. | Azacitidine process and polymorphs |
| ES2400779T3 (es) | 2008-08-06 | 2013-04-12 | Sicor, Inc. | Proceso para preparar un producto intermedio de azacitidina |
| KR101660549B1 (ko) * | 2008-08-08 | 2016-09-27 | 시노팜 타이완 리미티드 | ５―아자시토신 뉴클레오시드 및 이의 유도체의 제조 방법 |
| US20110042247A1 (en) | 2009-06-25 | 2011-02-24 | Chandrasekhar Kocherlakota | Formulations of azacitidine and its derivatives |
| IT1399195B1 (it) | 2010-03-30 | 2013-04-11 | Chemi Spa | Processo per la sintesi di azacitidina e decitabina |
-
2012
- 2012-03-29 MX MX2013010945A patent/MX2013010945A/es not_active Application Discontinuation
- 2012-03-29 BR BR112013025167A patent/BR112013025167A2/pt not_active IP Right Cessation
- 2012-03-29 EP EP12716820.1A patent/EP2691408B1/en active Active
- 2012-03-29 US US14/007,955 patent/US9951098B2/en active Active
- 2012-03-29 KR KR1020137028446A patent/KR20140019820A/ko not_active Withdrawn
- 2012-03-29 CN CN201280026401.3A patent/CN103619864A/zh active Pending
- 2012-03-29 WO PCT/US2012/031059 patent/WO2012135405A1/en not_active Ceased
- 2012-03-29 SG SG2013071915A patent/SG193622A1/en unknown
- 2012-03-29 AU AU2012236476A patent/AU2012236476A1/en not_active Abandoned
- 2012-03-29 JP JP2014502770A patent/JP6289361B2/ja active Active
- 2012-03-29 RU RU2013148580/04A patent/RU2013148580A/ru not_active Application Discontinuation
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2013
- 2013-09-23 ZA ZA2013/07142A patent/ZA201307142B/en unknown
- 2013-09-29 IL IL228604A patent/IL228604A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA201307142B (en) | 2015-11-25 |
| US20140128593A1 (en) | 2014-05-08 |
| IL228604A0 (en) | 2013-12-31 |
| MX2013010945A (es) | 2014-03-12 |
| CN103619864A (zh) | 2014-03-05 |
| RU2013148580A (ru) | 2015-05-10 |
| US9951098B2 (en) | 2018-04-24 |
| SG193622A1 (en) | 2013-11-29 |
| JP6289361B2 (ja) | 2018-03-07 |
| WO2012135405A1 (en) | 2012-10-04 |
| BR112013025167A2 (pt) | 2019-09-24 |
| EP2691408B1 (en) | 2017-06-28 |
| JP2014510755A (ja) | 2014-05-01 |
| KR20140019820A (ko) | 2014-02-17 |
| EP2691408A1 (en) | 2014-02-05 |
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| Date | Code | Title | Description |
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| PC1 | Assignment before grant (sect. 113) |
Owner name: CELGENE INTERNATIONAL SARL Free format text: FORMER APPLICANT(S): PHARMION LLC |
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| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |