CN102911165B - 顺-ftc的多晶型物及其它晶型 - Google Patents
顺-ftc的多晶型物及其它晶型 Download PDFInfo
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- CN102911165B CN102911165B CN201210146874.9A CN201210146874A CN102911165B CN 102911165 B CN102911165 B CN 102911165B CN 201210146874 A CN201210146874 A CN 201210146874A CN 102911165 B CN102911165 B CN 102911165B
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- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- NMJORVOYSJLJGU-UHFFFAOYSA-N methane clathrate Chemical compound C.C.C.C.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O NMJORVOYSJLJGU-UHFFFAOYSA-N 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002718 pyrimidine nucleoside Substances 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 150000003566 thiocarboxylic acids Chemical class 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- ZWYDDDAMNQQZHD-UHFFFAOYSA-L titanium(ii) chloride Chemical compound [Cl-].[Cl-].[Ti+2] ZWYDDDAMNQQZHD-UHFFFAOYSA-L 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical class OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D411/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D411/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D411/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27256001P | 2001-03-01 | 2001-03-01 | |
| US60/272560 | 2001-03-01 | ||
| US30960501P | 2001-08-02 | 2001-08-02 | |
| US60/309605 | 2001-08-02 | ||
| CN028082850A CN1503796B (zh) | 2001-03-01 | 2002-03-01 | 顺-ftc的多晶型物及其它晶型 |
Related Parent Applications (1)
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|---|---|---|---|
| CN028082850A Division CN1503796B (zh) | 2001-03-01 | 2002-03-01 | 顺-ftc的多晶型物及其它晶型 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102911165A CN102911165A (zh) | 2013-02-06 |
| CN102911165B true CN102911165B (zh) | 2016-08-17 |
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Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210146874.9A Expired - Fee Related CN102911165B (zh) | 2001-03-01 | 2002-03-01 | 顺-ftc的多晶型物及其它晶型 |
| CN2012101468804A Pending CN102942563A (zh) | 2001-03-01 | 2002-03-01 | 顺-ftc的多晶型物及其它晶型 |
| CN201210146877.2A Expired - Fee Related CN102911166B (zh) | 2001-03-01 | 2002-03-01 | 顺-ftc的多晶型物及其它晶型 |
| CN028082850A Expired - Fee Related CN1503796B (zh) | 2001-03-01 | 2002-03-01 | 顺-ftc的多晶型物及其它晶型 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101468804A Pending CN102942563A (zh) | 2001-03-01 | 2002-03-01 | 顺-ftc的多晶型物及其它晶型 |
| CN201210146877.2A Expired - Fee Related CN102911166B (zh) | 2001-03-01 | 2002-03-01 | 顺-ftc的多晶型物及其它晶型 |
| CN028082850A Expired - Fee Related CN1503796B (zh) | 2001-03-01 | 2002-03-01 | 顺-ftc的多晶型物及其它晶型 |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US6723728B2 (https=) |
| EP (3) | EP1574512B1 (https=) |
| JP (4) | JP5105689B2 (https=) |
| KR (4) | KR101150250B1 (https=) |
| CN (4) | CN102911165B (https=) |
| AT (2) | ATE312097T1 (https=) |
| AU (1) | AU2002335489B2 (https=) |
| CA (4) | CA2439831C (https=) |
| CY (2) | CY1107983T1 (https=) |
| DE (2) | DE60207850T2 (https=) |
| DK (2) | DK1389207T3 (https=) |
| ES (3) | ES2537007T3 (https=) |
| PT (2) | PT1903041E (https=) |
| WO (1) | WO2002070518A1 (https=) |
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| KR101150250B1 (ko) * | 2001-03-01 | 2012-06-12 | 아보트 래버러토리즈 | 시스-ｆｔｃ의 다형 및 기타 결정형 |
| TWI244393B (en) * | 2002-08-06 | 2005-12-01 | Idenix Pharmaceuticals Inc | Crystalline and amorphous forms of beta-L-2'-deoxythymidine |
| MXPA05007016A (es) | 2003-01-14 | 2005-09-12 | Gilead Sciences Inc | Composiciones y metodos para terapia antiviral de combinacion. |
| US6943249B2 (en) | 2003-03-17 | 2005-09-13 | Ash Stevens, Inc. | Methods for isolating crystalline Form I of 5-azacytidine |
| US6887855B2 (en) * | 2003-03-17 | 2005-05-03 | Pharmion Corporation | Forms of 5-azacytidine |
| US20060014949A1 (en) * | 2004-07-13 | 2006-01-19 | Supergen Inc. | Compositions and formulations of decitabine polymorphs and methods of use thereof |
| TWI375560B (en) | 2005-06-13 | 2012-11-01 | Gilead Sciences Inc | Composition comprising dry granulated emtricitabine and tenofovir df and method for making the same |
| TWI471145B (zh) | 2005-06-13 | 2015-02-01 | Bristol Myers Squibb & Gilead Sciences Llc | 單一式藥學劑量型 |
| WO2009005338A2 (en) * | 2007-07-05 | 2009-01-08 | Ultimorphix Technologies B.V. | Solid forms ult-i, ult-2 and ult-3 of emtricitabine |
| EP2350065A1 (en) | 2008-11-12 | 2011-08-03 | Lupin Ltd. | A novel polymorph of emtricitabine and a process for preparing of the same |
| EP2454244B1 (en) | 2009-07-15 | 2013-06-26 | Lupin Limited | An improved process for preparation of efavirenz |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992014743A2 (en) * | 1991-02-22 | 1992-09-03 | Emory University | Antiviral activity and resolution of 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane |
| CN1149871A (zh) * | 1994-04-23 | 1997-05-14 | 葛兰素集团有限公司 | 核苷类似物的非对映选择合成方法 |
| US5892025A (en) * | 1990-02-01 | 1999-04-06 | Emory University | Method of resolution and antiviral activity of 1,3-oxathiolane nucleoside enantiomers |
| WO2000009494A1 (en) * | 1998-08-12 | 2000-02-24 | Triangle Pharmaceuticals, Inc. | Method of manufacture of 1,3-oxathiolane nucleosides |
| EP0517145B1 (en) * | 1991-06-03 | 2002-01-30 | Glaxo Group Limited | Crystalline oxathiolane derivatives |
Family Cites Families (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US4476248A (en) | 1983-02-28 | 1984-10-09 | The Upjohn Company | Crystallization of ibuprofen |
| US5684153A (en) | 1984-08-16 | 1997-11-04 | Beecham Group Plc | Process for the preparation of purine derivatives |
| DE3485225D1 (de) | 1983-08-18 | 1991-12-05 | Beecham Group Plc | Antivirale guanin-derivate. |
| US5223263A (en) | 1988-07-07 | 1993-06-29 | Vical, Inc. | Liponucleotide-containing liposomes |
| CS264222B1 (en) | 1986-07-18 | 1989-06-13 | Holy Antonin | N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them |
| AU2526188A (en) | 1987-09-22 | 1989-04-18 | Regents Of The University Of California, The | Liposomal nucleoside analogues for treating aids |
| US5047407A (en) | 1989-02-08 | 1991-09-10 | Iaf Biochem International, Inc. | 2-substituted-5-substituted-1,3-oxathiolanes with antiviral properties |
| US5684164A (en) * | 1988-04-11 | 1997-11-04 | Biochem Pharma Inc. | Processes for preparing substituted 1,3-oxathiolanes with antiviral properties |
| US5041449A (en) | 1988-04-11 | 1991-08-20 | Iaf Biochem International, Inc. | 4-(nucleoside base)-substituted-1,3-dioxolanes useful for treatment of retroviral infections |
| NZ228645A (en) | 1988-04-11 | 1991-09-25 | Iaf Biochem Int | 1,3-dioxolane derivatives substituted in the 5th position by a purine or pyrimidine radical; treatment of viral infections |
| US5194654A (en) | 1989-11-22 | 1993-03-16 | Vical, Inc. | Lipid derivatives of phosphonoacids for liposomal incorporation and method of use |
| US5411947A (en) | 1989-06-28 | 1995-05-02 | Vestar, Inc. | Method of converting a drug to an orally available form by covalently bonding a lipid to the drug |
| US5463092A (en) | 1989-11-22 | 1995-10-31 | Vestar, Inc. | Lipid derivatives of phosphonacids for liposomal incorporation and method of use |
| US6703396B1 (en) * | 1990-02-01 | 2004-03-09 | Emory University | Method of resolution and antiviral activity of 1,3-oxathiolane nuclesoside enantiomers |
| US5204466A (en) | 1990-02-01 | 1993-04-20 | Emory University | Method and compositions for the synthesis of bch-189 and related compounds |
| US5914331A (en) | 1990-02-01 | 1999-06-22 | Emory University | Antiviral activity and resolution of 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane |
| US5700937A (en) | 1990-02-01 | 1997-12-23 | Emory University | Method for the synthesis, compositions and use of 2'-deoxy-5-fluoro-3'-thiacytidine and related compounds |
| GB9009861D0 (en) | 1990-05-02 | 1990-06-27 | Glaxo Group Ltd | Chemical compounds |
| AU7872491A (en) | 1990-05-07 | 1991-11-27 | Vical, Inc. | Lipid prodrugs of salicylate and nonsteroidal anti-inflammatory drugs |
| EP0531452A4 (en) | 1990-05-29 | 1993-06-09 | Vical, Inc. | Synthesis of glycerol di- and triphosphate derivatives |
| ATE131825T1 (de) | 1990-06-13 | 1996-01-15 | Arnold Glazier | Phosphorylierte prodrugs |
| US5674849A (en) | 1990-10-24 | 1997-10-07 | Allelix Biopharmaceuticals Inc. | Anti-viral compositions |
| US5256641A (en) | 1990-11-01 | 1993-10-26 | State Of Oregon | Covalent polar lipid-peptide conjugates for immunological targeting |
| US5543390A (en) | 1990-11-01 | 1996-08-06 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University | Covalent microparticle-drug conjugates for biological targeting |
| US5543389A (en) | 1990-11-01 | 1996-08-06 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education On Behalf Of The Oregon Health Sciences University, A Non Profit Organization | Covalent polar lipid-peptide conjugates for use in salves |
| US5149794A (en) | 1990-11-01 | 1992-09-22 | State Of Oregon | Covalent lipid-drug conjugates for drug targeting |
| US6228860B1 (en) * | 1990-11-13 | 2001-05-08 | Biochem Pharma Inc. | Substituted 1,3-oxathiolanes with antiviral properties |
| US5444063A (en) | 1990-12-05 | 1995-08-22 | Emory University | Enantiomerically pure β-D-dioxolane nucleosides with selective anti-Hepatitis B virus activity |
| US5925643A (en) | 1990-12-05 | 1999-07-20 | Emory University | Enantiomerically pure β-D-dioxolane-nucleosides |
| US5179104A (en) | 1990-12-05 | 1993-01-12 | University Of Georgia Research Foundation, Inc. | Process for the preparation of enantiomerically pure β-D-(-)-dioxolane-nucleosides |
| IL100502A (en) | 1991-01-03 | 1995-12-08 | Iaf Biochem Int | PHARMACEUTICAL PREPARATIONS CONTAINING CIS-4-AMINO-1-) 2-HYDROXIMETHIL-1,3-OXETYOLEN-5-IL (- |
| GB9104740D0 (en) | 1991-03-06 | 1991-04-17 | Wellcome Found | Antiviral nucleoside combination |
| IT1244501B (it) | 1991-03-22 | 1994-07-15 | Sigma Tau Ind Farmaceuti | Derivati amminoacilici e oligopeptidici dell'allopurinolo dotati di attivita' immunostimolante e composizioni farmaceutiche che li contengono |
| WO1992018517A1 (en) | 1991-04-17 | 1992-10-29 | Yale University | Method of treating or preventing hepatitis b virus |
| GB9110874D0 (en) | 1991-05-20 | 1991-07-10 | Iaf Biochem Int | Medicaments |
| ZA923640B (en) | 1991-05-21 | 1993-02-24 | Iaf Biochem Int | Processes for the diastereoselective synthesis of nucleosides |
| AU668873B2 (en) | 1991-07-12 | 1996-05-23 | Chimerix, Inc. | Antiviral liponucleosides: treatment of hepatitis B |
| US5554728A (en) | 1991-07-23 | 1996-09-10 | Nexstar Pharmaceuticals, Inc. | Lipid conjugates of therapeutic peptides and protease inhibitors |
| GB9116601D0 (en) * | 1991-08-01 | 1991-09-18 | Iaf Biochem Int | 1,3-oxathiolane nucleoside analogues |
| US6177435B1 (en) | 1992-05-13 | 2001-01-23 | Glaxo Wellcome Inc. | Therapeutic combinations |
| EP0746319A4 (en) | 1993-05-12 | 1997-11-05 | Karl Y Hostetler | ACYCLOVIR DERIVATIVES FOR TOPICAL USE |
| GB9311709D0 (en) | 1993-06-07 | 1993-07-21 | Iaf Biochem Int | Stereoselective synthesis of nucleoside analogues using bicycle intermediate |
| US5587362A (en) | 1994-01-28 | 1996-12-24 | Univ. Of Ga Research Foundation | L-nucleosides |
| US5808040A (en) | 1995-01-30 | 1998-09-15 | Yale University | L-nucleosides incorporated into polymeric structure for stabilization of oligonucleotides |
| SE9500872L (sv) * | 1995-03-10 | 1996-04-01 | Tony Wiseby | Anordning vid sikte för pilbåge |
| US5869461A (en) | 1995-03-16 | 1999-02-09 | Yale University | Reducing toxicity of L-nucleosides with D-nucleosides |
| DE19543707A1 (de) * | 1995-11-23 | 1997-05-28 | Inst Neue Mat Gemein Gmbh | Verfahren zum Konservieren von Papier |
| GB9525606D0 (en) | 1995-12-14 | 1996-02-14 | Iaf Biochem Int | Method and compositions for the synthesis of dioxolane nucleosides with - configuration |
| AU5127098A (en) | 1996-11-29 | 1998-06-22 | Smithkline Beecham Plc | Use of a combination of penciclovir and alpha-interferon in the manufacture of a medicament for the treatment of hepatitis |
| TW318283B (en) | 1996-12-09 | 1997-10-21 | United Microelectronics Corp | Multi-level read only memory structure and manufacturing method thereof |
| ATE267198T1 (de) | 1997-03-19 | 2004-06-15 | Univ Emory | Synthese und anti-hiv und anti-hepatitis virus aktivität von 1,3-oxaselenolan nucleosiden |
| AU773127B2 (en) | 1998-10-09 | 2004-05-20 | Altus Pharmaceuticals, Inc. | Non-homogeneous systems for the resolution of enantiomeric mixtures |
| KR101150250B1 (ko) * | 2001-03-01 | 2012-06-12 | 아보트 래버러토리즈 | 시스-ｆｔｃ의 다형 및 기타 결정형 |
| US6600044B2 (en) * | 2001-06-18 | 2003-07-29 | Brantford Chemicals Inc. | Process for recovery of the desired cis-1,3-oxathiolane nucleosides from their undesired trans-isomers |
-
2002
- 2002-03-01 KR KR1020107016624A patent/KR101150250B1/ko not_active Expired - Fee Related
- 2002-03-01 ES ES08000264.5T patent/ES2537007T3/es not_active Expired - Lifetime
- 2002-03-01 CN CN201210146874.9A patent/CN102911165B/zh not_active Expired - Fee Related
- 2002-03-01 PT PT80002645T patent/PT1903041E/pt unknown
- 2002-03-01 EP EP05076347A patent/EP1574512B1/en not_active Expired - Lifetime
- 2002-03-01 US US10/086,830 patent/US6723728B2/en not_active Expired - Lifetime
- 2002-03-01 AT AT02748367T patent/ATE312097T1/de active
- 2002-03-01 CN CN2012101468804A patent/CN102942563A/zh active Pending
- 2002-03-01 PT PT05076347T patent/PT1574512E/pt unknown
- 2002-03-01 KR KR1020087016003A patent/KR100927024B1/ko not_active Expired - Fee Related
- 2002-03-01 CN CN201210146877.2A patent/CN102911166B/zh not_active Expired - Fee Related
- 2002-03-01 KR KR10-2003-7011355A patent/KR20040002871A/ko not_active Ceased
- 2002-03-01 ES ES02748367T patent/ES2253544T3/es not_active Expired - Lifetime
- 2002-03-01 CN CN028082850A patent/CN1503796B/zh not_active Expired - Fee Related
- 2002-03-01 WO PCT/US2002/006184 patent/WO2002070518A1/en not_active Ceased
- 2002-03-01 AU AU2002335489A patent/AU2002335489B2/en not_active Ceased
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5892025A (en) * | 1990-02-01 | 1999-04-06 | Emory University | Method of resolution and antiviral activity of 1,3-oxathiolane nucleoside enantiomers |
| WO1992014743A2 (en) * | 1991-02-22 | 1992-09-03 | Emory University | Antiviral activity and resolution of 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane |
| CN1065065A (zh) * | 1991-02-22 | 1992-10-07 | 埃莫里大学 | 2-羟甲基-5-(5-氟胞嘧啶-1-基)-1，3-氧硫杂茂烷的制备方法 |
| EP0517145B1 (en) * | 1991-06-03 | 2002-01-30 | Glaxo Group Limited | Crystalline oxathiolane derivatives |
| CN1149871A (zh) * | 1994-04-23 | 1997-05-14 | 葛兰素集团有限公司 | 核苷类似物的非对映选择合成方法 |
| WO2000009494A1 (en) * | 1998-08-12 | 2000-02-24 | Triangle Pharmaceuticals, Inc. | Method of manufacture of 1,3-oxathiolane nucleosides |
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