CN102143967B - 阿德福韦酯的纯化方法 - Google Patents
阿德福韦酯的纯化方法 Download PDFInfo
- Publication number
- CN102143967B CN102143967B CN200980134900.2A CN200980134900A CN102143967B CN 102143967 B CN102143967 B CN 102143967B CN 200980134900 A CN200980134900 A CN 200980134900A CN 102143967 B CN102143967 B CN 102143967B
- Authority
- CN
- China
- Prior art keywords
- adefovir ester
- chemical formula
- adefovir
- purification process
- product
- 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.)
- Expired - Fee Related
Links
- 238000000746 purification Methods 0.000 title claims abstract description 46
- 238000000034 method Methods 0.000 title claims abstract description 31
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 title abstract description 16
- 229960003205 adefovir dipivoxil Drugs 0.000 title abstract description 8
- 239000000126 substance Substances 0.000 claims abstract description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 62
- 239000006227 byproduct Substances 0.000 claims abstract description 35
- 239000003960 organic solvent Substances 0.000 claims abstract description 29
- 229960001997 adefovir Drugs 0.000 claims description 143
- -1 adefovir ester Chemical class 0.000 claims description 140
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 123
- 239000007864 aqueous solution Substances 0.000 claims description 70
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 36
- 239000000243 solution Substances 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 13
- 239000007787 solid Substances 0.000 claims description 12
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 10
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 10
- 229940011051 isopropyl acetate Drugs 0.000 claims description 10
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 239000003513 alkali Substances 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 5
- 239000004215 Carbon black (E152) Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229920000642 polymer Polymers 0.000 claims description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 150000003839 salts Chemical class 0.000 abstract description 3
- 239000012046 mixed solvent Substances 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 239000002131 composite material Substances 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 59
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 34
- 239000012153 distilled water Substances 0.000 description 34
- 239000010410 layer Substances 0.000 description 30
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
- 239000012044 organic layer Substances 0.000 description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 21
- 239000011782 vitamin Substances 0.000 description 21
- 235000013343 vitamin Nutrition 0.000 description 21
- 229940088594 vitamin Drugs 0.000 description 21
- 229930003231 vitamin Natural products 0.000 description 21
- 150000003722 vitamin derivatives Chemical class 0.000 description 21
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 20
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- 238000010828 elution Methods 0.000 description 17
- 239000000945 filler Substances 0.000 description 17
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 14
- 229960001407 sodium bicarbonate Drugs 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 238000011084 recovery Methods 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 229910052814 silicon oxide Inorganic materials 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 230000006837 decompression Effects 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 230000005526 G1 to G0 transition Effects 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 4
- 235000010755 mineral Nutrition 0.000 description 4
- 239000011707 mineral Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- UKPTUJWPHNTYDJ-UHFFFAOYSA-N 4-chloro-2,2-dimethylbutanoic acid;chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl.OC(=O)C(C)(C)CCCl UKPTUJWPHNTYDJ-UHFFFAOYSA-N 0.000 description 1
- 241000700739 Hepadnaviridae Species 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 229940123527 Nucleotide reverse transcriptase inhibitor Drugs 0.000 description 1
- 240000001987 Pyrus communis Species 0.000 description 1
- 235000014443 Pyrus communis Nutrition 0.000 description 1
- SUPKOOSCJHTBAH-UHFFFAOYSA-N adefovir Chemical compound NC1=NC=NC2=C1N=CN2CCOCP(O)(O)=O SUPKOOSCJHTBAH-UHFFFAOYSA-N 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
- HTRXGEPDTFSKLI-UHFFFAOYSA-N butanoic acid;ethyl acetate Chemical compound CCCC(O)=O.CCOC(C)=O HTRXGEPDTFSKLI-UHFFFAOYSA-N 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229940097709 hepsera Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 1
- LFLZOWIFJOBEPN-UHFFFAOYSA-N nitrate, nitrate Chemical compound O[N+]([O-])=O.O[N+]([O-])=O LFLZOWIFJOBEPN-UHFFFAOYSA-N 0.000 description 1
- VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/025—Purification; Separation; Stabilisation; Desodorisation of organo-phosphorus compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (9)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20080089907 | 2008-09-11 | ||
KR10-2008-0089907 | 2008-09-11 | ||
KR1020090001395A KR20100031045A (ko) | 2008-09-11 | 2009-01-08 | 아데포비어 디피복실의 정제방법 |
KR10-2009-0001395 | 2009-01-08 | ||
PCT/KR2009/005150 WO2010030132A2 (ko) | 2008-09-11 | 2009-09-10 | 아데포비어 디피복실의 정제방법 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102143967A CN102143967A (zh) | 2011-08-03 |
CN102143967B true CN102143967B (zh) | 2015-02-04 |
Family
ID=42180843
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200980134900.2A Expired - Fee Related CN102143967B (zh) | 2008-09-11 | 2009-09-10 | 阿德福韦酯的纯化方法 |
Country Status (7)
Country | Link |
---|---|
US (1) | US20110207928A1 (zh) |
EP (1) | EP2327708A4 (zh) |
JP (2) | JP5390617B2 (zh) |
KR (2) | KR20100031045A (zh) |
CN (1) | CN102143967B (zh) |
TW (1) | TWI372761B (zh) |
WO (1) | WO2010030132A2 (zh) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITMI20071594A1 (it) * | 2007-08-02 | 2009-02-03 | Solmag Spa | Forma cristallina monoidrata di adefovir dipivoxil |
KR20100031045A (ko) * | 2008-09-11 | 2010-03-19 | 씨제이제일제당 (주) | 아데포비어 디피복실의 정제방법 |
KR20100032803A (ko) * | 2008-09-18 | 2010-03-26 | 씨제이제일제당 (주) | 아데포비어디피복실의 개선된 제조방법 |
KR101247653B1 (ko) * | 2010-11-08 | 2013-04-01 | (주) 성운파마코피아 | 아데포비어 디피복실 제조방법 |
US8969588B2 (en) * | 2012-06-05 | 2015-03-03 | Gilead Pharmasset Llc | Solid forms of an antiviral compound |
CN103880884A (zh) * | 2014-03-21 | 2014-06-25 | 浙江苏泊尔制药有限公司 | 一种高纯度富马酸泰诺福韦酯的制备方法 |
TWI609745B (zh) * | 2015-07-02 | 2018-01-01 | 嘉新精密有限公司 | 側向夾持的彈性定位塊結構 |
CN105294762A (zh) * | 2015-11-13 | 2016-02-03 | 中国药科大学 | 阿德福韦酯杂质的制备方法 |
CN106167503B (zh) * | 2016-07-07 | 2018-06-22 | 福建广生堂药业股份有限公司 | 一种阿德福韦酯羟甲基杂质的制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5663159A (en) * | 1990-09-14 | 1997-09-02 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Prodrugs of phosphonates |
CN1935818A (zh) * | 2006-09-22 | 2007-03-28 | 闫敬武 | 阿德福韦酯新晶态、晶态组合物、制备方法及应用 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE277936T1 (de) | 1997-07-25 | 2004-10-15 | Gilead Sciences Inc | Verfahren zur herstellung von adefovir dipivoxil |
ZA986614B (en) | 1997-07-25 | 1999-01-27 | Gilead Sciences | Nucleotide analog composition |
TWI230618B (en) | 1998-12-15 | 2005-04-11 | Gilead Sciences Inc | Pharmaceutical compositions of 9-[2-[[bis[(pivaloyloxy)methyl]phosphono]methoxy]ethyl]adenine and tablets or capsules containing the same |
KR20100031045A (ko) * | 2008-09-11 | 2010-03-19 | 씨제이제일제당 (주) | 아데포비어 디피복실의 정제방법 |
KR100983322B1 (ko) * | 2008-09-17 | 2010-09-20 | 씨제이제일제당 (주) | 아데포비어 디피복실의 안정화된 고체 분산체 및 이의 제조 방법 |
KR20100032803A (ko) * | 2008-09-18 | 2010-03-26 | 씨제이제일제당 (주) | 아데포비어디피복실의 개선된 제조방법 |
-
2009
- 2009-01-08 KR KR1020090001395A patent/KR20100031045A/ko active Search and Examination
- 2009-09-10 EP EP09813254A patent/EP2327708A4/en not_active Withdrawn
- 2009-09-10 WO PCT/KR2009/005150 patent/WO2010030132A2/ko active Application Filing
- 2009-09-10 US US13/063,449 patent/US20110207928A1/en not_active Abandoned
- 2009-09-10 CN CN200980134900.2A patent/CN102143967B/zh not_active Expired - Fee Related
- 2009-09-10 KR KR1020090085444A patent/KR100970434B1/ko active IP Right Grant
- 2009-09-10 JP JP2011526814A patent/JP5390617B2/ja not_active Expired - Fee Related
- 2009-09-11 TW TW098130789A patent/TWI372761B/zh not_active IP Right Cessation
-
2013
- 2013-10-09 JP JP2013212040A patent/JP2014114271A/ja active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5663159A (en) * | 1990-09-14 | 1997-09-02 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Prodrugs of phosphonates |
CN1935818A (zh) * | 2006-09-22 | 2007-03-28 | 闫敬武 | 阿德福韦酯新晶态、晶态组合物、制备方法及应用 |
Also Published As
Publication number | Publication date |
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JP5390617B2 (ja) | 2014-01-15 |
WO2010030132A2 (ko) | 2010-03-18 |
TWI372761B (en) | 2012-09-21 |
KR20100031045A (ko) | 2010-03-19 |
JP2012512137A (ja) | 2012-05-31 |
KR20100031085A (ko) | 2010-03-19 |
TW201016713A (en) | 2010-05-01 |
KR100970434B1 (ko) | 2010-07-15 |
US20110207928A1 (en) | 2011-08-25 |
WO2010030132A3 (ko) | 2010-06-10 |
JP2014114271A (ja) | 2014-06-26 |
CN102143967A (zh) | 2011-08-03 |
EP2327708A4 (en) | 2011-11-30 |
EP2327708A2 (en) | 2011-06-01 |
WO2010030132A9 (ko) | 2010-08-05 |
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