CA2540158C - Method for the preparation of 2-halo-2'-deoxyadenosine compounds from 2'-deoxyguanosine - Google Patents
Method for the preparation of 2-halo-2'-deoxyadenosine compounds from 2'-deoxyguanosine Download PDFInfo
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- CA2540158C CA2540158C CA2540158A CA2540158A CA2540158C CA 2540158 C CA2540158 C CA 2540158C CA 2540158 A CA2540158 A CA 2540158A CA 2540158 A CA2540158 A CA 2540158A CA 2540158 C CA2540158 C CA 2540158C
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- chloro
- amino
- substituted
- sulfonyl
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- 238000000034 method Methods 0.000 title claims abstract description 48
- YKBGVTZYEHREMT-UHFFFAOYSA-N 2'-deoxyguanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1CC(O)C(CO)O1 YKBGVTZYEHREMT-UHFFFAOYSA-N 0.000 title abstract description 26
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 title abstract description 10
- VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 title abstract description 8
- 238000002360 preparation method Methods 0.000 title description 14
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 claims abstract description 29
- 125000006239 protecting group Chemical group 0.000 claims abstract description 15
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 25
- 238000006193 diazotization reaction Methods 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 229910021529 ammonia Inorganic materials 0.000 claims description 9
- 238000006073 displacement reaction Methods 0.000 claims description 7
- 125000001475 halogen functional group Chemical group 0.000 claims description 6
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000000269 nucleophilic effect Effects 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 3
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 claims description 2
- 229960002436 cladribine Drugs 0.000 abstract description 10
- 206010028980 Neoplasm Diseases 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
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- 229940125782 compound 2 Drugs 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000002777 nucleoside Substances 0.000 description 15
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- 239000003153 chemical reaction reagent Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- 238000005915 ammonolysis reaction Methods 0.000 description 10
- 125000003118 aryl group Chemical group 0.000 description 10
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 10
- HBJGQJWNMZDFKL-UHFFFAOYSA-N 2-chloro-7h-purin-6-amine Chemical compound NC1=NC(Cl)=NC2=C1NC=N2 HBJGQJWNMZDFKL-UHFFFAOYSA-N 0.000 description 9
- LFZDBHUQQUCZJO-UHFFFAOYSA-M benzyl(triethyl)azanium;nitrite Chemical compound [O-]N=O.CC[N+](CC)(CC)CC1=CC=CC=C1 LFZDBHUQQUCZJO-UHFFFAOYSA-M 0.000 description 9
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- -1 2-aminopurine nucleoside Chemical class 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
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- 238000010511 deprotection reaction Methods 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 6
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- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical class NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
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- 239000012074 organic phase Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- RMFWVOLULURGJI-UHFFFAOYSA-N 2,6-dichloro-7h-purine Chemical compound ClC1=NC(Cl)=C2NC=NC2=N1 RMFWVOLULURGJI-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- QZGYRDUIRRZJHS-IVZWLZJFSA-N [(2r,3s,5r)-3-acetyloxy-5-(2-amino-6-oxo-3h-purin-9-yl)oxolan-2-yl]methyl acetate Chemical compound C1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1N1C(N=C(N)NC2=O)=C2N=C1 QZGYRDUIRRZJHS-IVZWLZJFSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000005228 aryl sulfonate group Chemical group 0.000 description 3
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
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- 239000000543 intermediate Substances 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 150000002826 nitrites Chemical class 0.000 description 3
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
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- 125000000547 substituted alkyl group Chemical group 0.000 description 3
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- 230000009466 transformation Effects 0.000 description 3
- 238000002211 ultraviolet spectrum Methods 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
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- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
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- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
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- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 2
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- NOLHIMIFXOBLFF-KVQBGUIXSA-N (2r,3s,5r)-5-(2,6-diaminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound C12=NC(N)=NC(N)=C2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 NOLHIMIFXOBLFF-KVQBGUIXSA-N 0.000 description 1
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- 150000002500 ions Chemical class 0.000 description 1
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
- 208000019420 lymphoid neoplasm Diseases 0.000 description 1
- 201000000564 macroglobulinemia Diseases 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- VRJUWTSINZCINA-UHFFFAOYSA-N n'-(2-chloro-7h-purin-6-yl)-n,n-dimethylmethanimidamide Chemical compound CN(C)C=NC1=NC(Cl)=NC2=C1NC=N2 VRJUWTSINZCINA-UHFFFAOYSA-N 0.000 description 1
- CSDTZUBPSYWZDX-UHFFFAOYSA-N n-pentyl nitrite Chemical compound CCCCCON=O CSDTZUBPSYWZDX-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- BMNDJWSIKZECMH-UHFFFAOYSA-N nitrosyl bromide Chemical compound BrN=O BMNDJWSIKZECMH-UHFFFAOYSA-N 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UYLWKSJTHLRFBX-UHFFFAOYSA-N purin-6-one Chemical class O=C1N=CN=C2N=CN=C12 UYLWKSJTHLRFBX-UHFFFAOYSA-N 0.000 description 1
- 239000002212 purine nucleoside Substances 0.000 description 1
- 150000003834 purine nucleoside derivatives Chemical class 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical group ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- C07H19/16—Purine radicals
- C07H19/167—Purine radicals with ribosyl as the saccharide radical
-
- 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
- C07H19/16—Purine radicals
- C07H19/173—Purine radicals with 2-deoxyribosyl as the saccharide radical
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41391502P | 2002-09-25 | 2002-09-25 | |
| US60/413,915 | 2002-09-25 | ||
| US41632902P | 2002-10-04 | 2002-10-04 | |
| US60/416,329 | 2002-10-04 | ||
| PCT/US2003/030386 WO2004028462A2 (en) | 2002-09-25 | 2003-09-25 | Method for the preparation of 2-halo-2'-deoxyadenosine compounds from 2'-deoxyguanosine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2540158A1 CA2540158A1 (en) | 2004-04-08 |
| CA2540158C true CA2540158C (en) | 2011-07-05 |
Family
ID=32045263
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2540158A Expired - Fee Related CA2540158C (en) | 2002-09-25 | 2003-09-25 | Method for the preparation of 2-halo-2'-deoxyadenosine compounds from 2'-deoxyguanosine |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US7572909B2 (enExample) |
| EP (1) | EP1556400B1 (enExample) |
| JP (2) | JP4757632B2 (enExample) |
| AU (1) | AU2003275267A1 (enExample) |
| CA (1) | CA2540158C (enExample) |
| ES (1) | ES2405825T3 (enExample) |
| WO (1) | WO2004028462A2 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4757632B2 (ja) | 2002-09-25 | 2011-08-24 | ブリガム ヤング ユニバーシティー | ２’−デオキシグアノシンから２−クロロ−２’−デオキシアデノシンを調製する方法 |
| DK2805723T3 (da) | 2004-12-22 | 2018-01-29 | Merck Serono Sa | Cladribin-regime til behandling af multipel sclerose |
| CA2649810A1 (en) | 2006-05-24 | 2007-11-29 | Laboratoires Serono S.A. | Cladribine regimen for treating multiple sclerosis |
| SI1932918T1 (sl) | 2006-12-15 | 2010-02-26 | Explora Lab Sa | Postopek izdelave kladribina |
| RU2324699C1 (ru) * | 2007-02-05 | 2008-05-20 | Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова Россиийской Академии Наук | СПОСОБ ПОЛУЧЕНИЯ 2,6-ДИХЛОР-9-(2,3,5-ТРИ-O-АЦЕТИЛ-β-D-РИБОФУРАНОЗИЛ)ПУРИНА |
| EP2343074A1 (en) | 2009-12-23 | 2011-07-13 | Merck Serono S.A. | Use of purine analogues for treating airway diseases |
| RU2649828C1 (ru) * | 2017-06-07 | 2018-04-04 | Государственное бюджетное учреждение здравоохранения города Москвы Московский клинический научно-практический центр им. А.С. Логинова Департамента здравоохранения города Москвы | Способ лечения волосатоклеточного лейкоза |
| KR20250005506A (ko) | 2017-11-24 | 2025-01-09 | 메르크 파텐트 게엠베하 | 진행 형태의 다발성 경화증의 치료에서 사용을 위한 클라드리빈 용법 |
| IL301246A (en) | 2020-09-10 | 2023-05-01 | Merck Patent Gmbh | Cladribine treatment regimen |
| EP4302091A1 (en) | 2021-03-03 | 2024-01-10 | Ares Trading S.A. | Improved treatment methods using dmds for the treatment of autoimmune diseases, and biomarker for predicting and/or optimising said treatment methods |
| WO2025125527A1 (en) | 2023-12-14 | 2025-06-19 | Ares Trading S.A. | Cladribine regimen for treating myasthenia gravis |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1269659A (en) * | 1984-08-06 | 1990-05-29 | Brigham Young University | Method for the production of 2'-deoxyadenosine compounds |
| US4760137A (en) | 1984-08-06 | 1988-07-26 | Brigham Young University | Method for the production of 2'-deoxyadenosine compounds |
| DE3924424A1 (de) * | 1989-07-24 | 1991-01-31 | Boehringer Mannheim Gmbh | Nucleosid-derivate, verfahren zu deren herstellung, deren verwendung als arzneimittel sowie deren verwendung bei der nucleinsaeure-sequenzierung |
| US5208327A (en) * | 1991-12-18 | 1993-05-04 | Ortho Pharmaceutical Corporation | Intermediates useful in a synthesis of 2-chloro-2'-deoxyadenosine |
| US5602246A (en) * | 1992-11-25 | 1997-02-11 | Schering Aktiengesellschaft | Process for the preparation of fludarabine or fludarabine phosphate from guanosine |
| US6252061B1 (en) * | 1998-03-23 | 2001-06-26 | Reliable Biopharmaceutical, Inc. | Process for the production of 2-halo-6-aminopurine derivatives |
| US6541626B2 (en) * | 2001-04-17 | 2003-04-01 | Isis Pharmaceuticals, Inc. | Process for selective N-acylation of purine nucleosides |
| JP4757632B2 (ja) * | 2002-09-25 | 2011-08-24 | ブリガム ヤング ユニバーシティー | ２’−デオキシグアノシンから２−クロロ−２’−デオキシアデノシンを調製する方法 |
-
2003
- 2003-09-25 JP JP2005501990A patent/JP4757632B2/ja not_active Expired - Fee Related
- 2003-09-25 AU AU2003275267A patent/AU2003275267A1/en not_active Abandoned
- 2003-09-25 EP EP03759541.0A patent/EP1556400B1/en not_active Expired - Lifetime
- 2003-09-25 CA CA2540158A patent/CA2540158C/en not_active Expired - Fee Related
- 2003-09-25 US US10/529,106 patent/US7572909B2/en not_active Expired - Lifetime
- 2003-09-25 ES ES03759541T patent/ES2405825T3/es not_active Expired - Lifetime
- 2003-09-25 WO PCT/US2003/030386 patent/WO2004028462A2/en not_active Ceased
-
2009
- 2009-07-02 US US12/497,287 patent/US8466275B2/en not_active Expired - Fee Related
-
2011
- 2011-03-09 JP JP2011051093A patent/JP2011116782A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP1556400A4 (en) | 2009-11-18 |
| US8466275B2 (en) | 2013-06-18 |
| US20090270604A1 (en) | 2009-10-29 |
| US7572909B2 (en) | 2009-08-11 |
| JP4757632B2 (ja) | 2011-08-24 |
| US20070032645A1 (en) | 2007-02-08 |
| JP2011116782A (ja) | 2011-06-16 |
| AU2003275267A1 (en) | 2004-04-19 |
| WO2004028462A3 (en) | 2004-06-10 |
| CA2540158A1 (en) | 2004-04-08 |
| EP1556400A2 (en) | 2005-07-27 |
| WO2004028462A2 (en) | 2004-04-08 |
| ES2405825T3 (es) | 2013-06-03 |
| EP1556400B1 (en) | 2013-05-01 |
| AU2003275267A8 (en) | 2004-04-19 |
| JP2006508183A (ja) | 2006-03-09 |
| WO2004028462A9 (en) | 2010-08-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20180925 |