FI114471B - Menetelmä nukleosidin 2', 3' -dideoksi-3' -tiapyrimidiini beta-isomeerin valmistamiseski - Google Patents
Menetelmä nukleosidin 2', 3' -dideoksi-3' -tiapyrimidiini beta-isomeerin valmistamiseski Download PDFInfo
- Publication number
- FI114471B FI114471B FI923446A FI923446A FI114471B FI 114471 B FI114471 B FI 114471B FI 923446 A FI923446 A FI 923446A FI 923446 A FI923446 A FI 923446A FI 114471 B FI114471 B FI 114471B
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- FI
- Finland
- Prior art keywords
- formula
- nucleoside
- process according
- bch
- oxathiolane
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 32
- 239000002777 nucleoside Substances 0.000 title claims abstract description 29
- 150000003833 nucleoside derivatives Chemical class 0.000 title claims abstract description 20
- 230000008569 process Effects 0.000 title claims description 20
- 238000002360 preparation method Methods 0.000 title abstract description 8
- 230000000707 stereoselective effect Effects 0.000 claims abstract description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000006239 protecting group Chemical group 0.000 claims description 15
- 125000002252 acyl group Chemical group 0.000 claims description 12
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
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- 108090000790 Enzymes Proteins 0.000 claims description 10
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 10
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims description 10
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims description 10
- 150000002596 lactones Chemical class 0.000 claims description 9
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- WGCNASOHLSPBMP-UHFFFAOYSA-N Glycolaldehyde Chemical compound OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
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- 229910052736 halogen Chemical group 0.000 claims description 6
- 150000002367 halogens Chemical group 0.000 claims description 6
- WJJSZTJGFCFNKI-UHFFFAOYSA-N 1,3-oxathiolane Chemical compound C1CSCO1 WJJSZTJGFCFNKI-UHFFFAOYSA-N 0.000 claims description 5
- 239000000460 chlorine Chemical group 0.000 claims description 5
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 5
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- 239000003638 chemical reducing agent Substances 0.000 claims description 4
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- OOFGXDQWDNJDIS-UHFFFAOYSA-N oxathiolane Chemical compound C1COSC1 OOFGXDQWDNJDIS-UHFFFAOYSA-N 0.000 claims description 4
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 claims description 3
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- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 claims description 3
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- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
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- LNBHUCHAFZUEGJ-UHFFFAOYSA-N europium(3+) Chemical class [Eu+3] LNBHUCHAFZUEGJ-UHFFFAOYSA-N 0.000 description 1
- 150000002221 fluorine Chemical class 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000002035 hexane extract Substances 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
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- 230000005764 inhibitory process Effects 0.000 description 1
- 238000013101 initial test Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
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- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
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- 229910052717 sulfur Inorganic materials 0.000 description 1
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- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000005000 thioaryl group Chemical group 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical class CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- WJTPULFEHRBUCP-UHFFFAOYSA-N trimethylsilyl perchlorate Chemical compound C[Si](C)(C)OCl(=O)(=O)=O WJTPULFEHRBUCP-UHFFFAOYSA-N 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
- C07D327/02—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms one oxygen atom and one sulfur atom
- C07D327/04—Five-membered rings
-
- 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
-
- 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
- C07H19/06—Pyrimidine radicals
-
- 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
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/473,318 US5204466A (en) | 1990-02-01 | 1990-02-01 | Method and compositions for the synthesis of bch-189 and related compounds |
| US47331890 | 1990-02-01 | ||
| US9100685 | 1991-01-31 | ||
| PCT/US1991/000685 WO1991011186A1 (en) | 1990-02-01 | 1991-01-31 | Method and compositions for the synthesis of bch-189 and related compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI923446A FI923446A (fi) | 1992-07-30 |
| FI923446A0 FI923446A0 (fi) | 1992-07-30 |
| FI114471B true FI114471B (fi) | 2004-10-29 |
Family
ID=23879071
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI923446A FI114471B (fi) | 1990-02-01 | 1992-07-30 | Menetelmä nukleosidin 2', 3' -dideoksi-3' -tiapyrimidiini beta-isomeerin valmistamiseski |
| FI20030933A FI116222B (fi) | 1990-02-01 | 2003-06-24 | 1,3-oksatiolaani |
| FI20050672A FI121069B (fi) | 1990-02-01 | 2005-06-22 | Menetelmä 2´,3´-dideoksi-3´-tia-pyrimidiininukleosidin käsittävän isomeeriseoksen valmistamiseksi |
| FI20060622A FI20060622A (fi) | 1990-02-01 | 2006-06-27 | Menetelmä terapeuttisesti käyttökelpoisen beta-2-hydroksimetyyli-5-(5-fluori-sytosin-1-yyli)-1,3-oksatiolaanin valmistamiseksi |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI20030933A FI116222B (fi) | 1990-02-01 | 2003-06-24 | 1,3-oksatiolaani |
| FI20050672A FI121069B (fi) | 1990-02-01 | 2005-06-22 | Menetelmä 2´,3´-dideoksi-3´-tia-pyrimidiininukleosidin käsittävän isomeeriseoksen valmistamiseksi |
| FI20060622A FI20060622A (fi) | 1990-02-01 | 2006-06-27 | Menetelmä terapeuttisesti käyttökelpoisen beta-2-hydroksimetyyli-5-(5-fluori-sytosin-1-yyli)-1,3-oksatiolaanin valmistamiseksi |
Country Status (22)
| Country | Link |
|---|---|
| US (8) | US5204466A (de) |
| EP (3) | EP0872237B1 (de) |
| JP (6) | JPH07618B2 (de) |
| KR (2) | KR100381705B1 (de) |
| AT (1) | ATE170750T1 (de) |
| AU (6) | AU658136C (de) |
| BG (1) | BG62236B1 (de) |
| CA (3) | CA2075189C (de) |
| DE (4) | DE513200T1 (de) |
| DK (2) | DK0872237T3 (de) |
| ES (2) | ES2279559T3 (de) |
| FI (4) | FI114471B (de) |
| GR (1) | GR950300024T1 (de) |
| HK (1) | HK1014664A1 (de) |
| HU (4) | HU9202496D0 (de) |
| LU (1) | LU91073I2 (de) |
| MC (1) | MC2233A1 (de) |
| NL (1) | NL300148I2 (de) |
| NO (6) | NO923014L (de) |
| RO (1) | RO108564B1 (de) |
| RU (1) | RU2125558C1 (de) |
| WO (1) | WO1991011186A1 (de) |
Families Citing this family (150)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6903224B2 (en) | 1988-04-11 | 2005-06-07 | Biochem Pharma Inc. | Substituted 1,3-oxathiolanes |
| US5684164A (en) * | 1988-04-11 | 1997-11-04 | Biochem Pharma Inc. | Processes for preparing substituted 1,3-oxathiolanes with antiviral properties |
| US7119202B1 (en) * | 1989-02-08 | 2006-10-10 | Glaxo Wellcome Inc. | Substituted-1,3-oxathiolanes and substituted-1,3-dioxolanes with antiviral properties |
| US5047407A (en) * | 1989-02-08 | 1991-09-10 | Iaf Biochem International, Inc. | 2-substituted-5-substituted-1,3-oxathiolanes with antiviral properties |
| US5466806A (en) * | 1989-02-08 | 1995-11-14 | Biochem Pharma Inc. | Processes for preparing substituted 1,3-oxathiolanes with antiviral properties |
| US6350753B1 (en) | 1988-04-11 | 2002-02-26 | Biochem Pharma Inc. | 2-Substituted-4-substituted-1,3-dioxolanes and use thereof |
| HU226137B1 (en) * | 1989-02-08 | 2008-05-28 | Shire Canada Inc | Process for preparing substituted 1,3-oxathiolanes with antiviral properties |
| US6703396B1 (en) * | 1990-02-01 | 2004-03-09 | Emory University | Method of resolution and antiviral activity of 1,3-oxathiolane nuclesoside enantiomers |
| US20090239887A1 (en) * | 1990-02-01 | 2009-09-24 | Emory University | Method of resolution and antiviral activity of 1,3-oxathiolane nucleoside enantiomers |
| US5827727A (en) * | 1990-02-01 | 1998-10-27 | Emory University | Method of resolution of 1,3-oxathiolane nucleoside enantiomers |
| US5276151A (en) * | 1990-02-01 | 1994-01-04 | Emory University | Method of synthesis of 1,3-dioxolane nucleosides |
| 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 |
| US5204466A (en) * | 1990-02-01 | 1993-04-20 | Emory University | Method and compositions for the synthesis of bch-189 and related compounds |
| GB9009861D0 (en) * | 1990-05-02 | 1990-06-27 | Glaxo Group Ltd | Chemical compounds |
| US5925643A (en) * | 1990-12-05 | 1999-07-20 | Emory University | Enantiomerically pure β-D-dioxolane-nucleosides |
| US5444063A (en) * | 1990-12-05 | 1995-08-22 | Emory University | Enantiomerically pure β-D-dioxolane nucleosides with selective anti-Hepatitis B virus activity |
| 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 (- |
| IL100965A (en) * | 1991-02-22 | 1999-12-31 | Univ Emory | 2 - Hydroxymethyl - 5 -) 5 - Fluorocytocin - 1 - Eyal (- 1, 3 - Oxathiolane, its resolution and pharmaceuticals containing it |
| GB9104740D0 (en) * | 1991-03-06 | 1991-04-17 | Wellcome Found | Antiviral nucleoside combination |
| US6812233B1 (en) * | 1991-03-06 | 2004-11-02 | Emory University | Therapeutic nucleosides |
| IL101144A (en) * | 1991-03-06 | 1996-09-12 | Wellcome Found | Pharmaceutical preparations containing 1 -) 2 -) hydroxymethyl (- 1, 3 - oxathiolan-5 - il (5) fluorescitosin and its derivatives for the treatment of their hepatitis B virus infections |
| US5817667A (en) * | 1991-04-17 | 1998-10-06 | University Of Georgia Research Foudation | Compounds and methods for the treatment of cancer |
| GB9109506D0 (en) * | 1991-05-02 | 1991-06-26 | Wellcome Found | Therapeutic nucleosides |
| 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 |
| GB9111902D0 (en) * | 1991-06-03 | 1991-07-24 | Glaxo Group Ltd | Chemical compounds |
| GB9116601D0 (en) * | 1991-08-01 | 1991-09-18 | Iaf Biochem Int | 1,3-oxathiolane nucleoside analogues |
| US20050192299A1 (en) * | 1992-04-16 | 2005-09-01 | Yung-Chi Cheng | Method of treating or preventing hepatitis B virus |
| GB9311709D0 (en) * | 1993-06-07 | 1993-07-21 | Iaf Biochem Int | Stereoselective synthesis of nucleoside analogues using bicycle intermediate |
| WO1995007086A1 (en) * | 1993-09-10 | 1995-03-16 | Emory University | Nucleosides with anti-hepatitis b virus activity |
| US20020120130A1 (en) * | 1993-09-10 | 2002-08-29 | Gilles Gosselin | 2' or 3' -deoxy and 2', 3' -dideoxy-beta-L-pentofuranonucleo-side compounds, method of preparation and application in therapy, especially as anti- viral agents |
| US5587362A (en) * | 1994-01-28 | 1996-12-24 | Univ. Of Ga Research Foundation | L-nucleosides |
| IL113432A (en) * | 1994-04-23 | 2000-11-21 | Glaxo Group Ltd | Process for the diastereoselective synthesis of nucleoside analogues |
| IL115156A (en) * | 1994-09-06 | 2000-07-16 | Univ Georgia | Pharmaceutical compositions for the treatment of cancer comprising 1-(2-hydroxymethyl-1,3-dioxolan-4-yl) cytosines |
| US6391859B1 (en) | 1995-01-27 | 2002-05-21 | Emory University | [5-Carboxamido or 5-fluoro]-[2′,3′-unsaturated or 3′-modified]-pyrimidine nucleosides |
| US5703058A (en) * | 1995-01-27 | 1997-12-30 | Emory University | Compositions containing 5-fluoro-2',3'-didehydro-2',3'-dideoxycytidine or a mono-, di-, or triphosphate thereof and a second antiviral agent |
| US5808040A (en) * | 1995-01-30 | 1998-09-15 | Yale University | L-nucleosides incorporated into polymeric structure for stabilization of oligonucleotides |
| US6689761B1 (en) | 1995-02-01 | 2004-02-10 | Merck & Co., Inc. | Combination therapy for HIV infection |
| MY115461A (en) | 1995-03-30 | 2003-06-30 | Wellcome Found | Synergistic combinations of zidovudine, 1592u89 and 3tc |
| GB9506644D0 (en) * | 1995-03-31 | 1995-05-24 | Wellcome Found | Preparation of nucleoside analogues |
| DE19514523A1 (de) * | 1995-04-12 | 1996-10-17 | Schering Ag | Neue Cytosin- und Cytidinderivate |
| DE69636734T2 (de) | 1995-06-07 | 2007-10-18 | Emory University | Nucleoside mit anti-hepatitis b virus wirksamkeit |
| NZ333099A (en) | 1996-06-25 | 2000-06-23 | Glaxo Group Ltd | synergistic combinations comprising 141W94, zidovudine and 3TC for use in the treatment of HIV |
| US5753789A (en) * | 1996-07-26 | 1998-05-19 | Yale University | Oligonucleotides containing L-nucleosides |
| US6113920A (en) * | 1996-10-31 | 2000-09-05 | Glaxo Wellcome Inc. | Pharmaceutical compositions |
| US6022876A (en) * | 1996-11-15 | 2000-02-08 | Yale University | L-β-dioxolane uridine analogs and methods for treating and preventing Epstein-Barr virus infections |
| US5792773A (en) * | 1996-11-15 | 1998-08-11 | Yale University | L-β-dioxolane uridine analog administration for treating Epstein-Barr virus infection |
| ATE267198T1 (de) * | 1997-03-19 | 2004-06-15 | Univ Emory | Synthese und anti-hiv und anti-hepatitis virus aktivität von 1,3-oxaselenolan nucleosiden |
| US6410546B1 (en) | 1997-04-07 | 2002-06-25 | Triangle Pharmaceuticals, Inc. | Use of MKC-442 in combination with other antiviral agents |
| EP1754710A3 (de) | 1998-02-25 | 2007-12-19 | Emory University | 2'-Fluoronukleoside |
| EA200700564A1 (ru) | 1998-02-25 | 2007-08-31 | Эмори Юниверсити | 2`-фторнуклеозиды |
| US6444652B1 (en) | 1998-08-10 | 2002-09-03 | Novirio Pharmaceuticals Limited | β-L-2'-deoxy-nucleosides for the treatment of hepatitis B |
| DK2415776T3 (en) * | 1998-08-10 | 2016-07-04 | Novartis Ag | Beta-L-2'-deoxy nucleosides for the treatment of Hepatitis B |
| JP4249393B2 (ja) * | 1998-08-12 | 2009-04-02 | トライアングル・ファーマシューティカルズ，インコーポレイテッド | １，３−オキサチオランヌクレオチドの製造方法 |
| US6979561B1 (en) | 1998-10-09 | 2005-12-27 | Gilead Sciences, Inc. | Non-homogeneous systems for the resolution of enantiomeric mixtures |
| CN1666742A (zh) | 1998-11-02 | 2005-09-14 | 三角药物公司 | 对乙型肝炎病毒的联合治疗 |
| US6407077B1 (en) | 1998-11-05 | 2002-06-18 | Emory University | β-L nucleosides for the treatment of HIV infection |
| KR100618028B1 (ko) | 1998-11-05 | 2006-08-30 | 쌍트르 나쉬오날 드 라 르쉐르스 쉬앙티피끄 | 항-ｂ형 간염 활성을 가진 뉴클레오시드 |
| CA2355712C (en) | 1998-12-23 | 2009-03-17 | Shire Biochem Inc. | Antiviral nucleoside analogues |
| US7205404B1 (en) | 1999-03-05 | 2007-04-17 | Metabasis Therapeutics, Inc. | Phosphorus-containing prodrugs |
| US6653318B1 (en) * | 1999-07-21 | 2003-11-25 | Yale University | 5-(E)-Bromovinyl uracil analogues and related pyrimidine nucleosides as anti-viral agents and methods of use |
| WO2001034618A2 (en) * | 1999-11-12 | 2001-05-17 | Pharmasset Limited | Synthesis of 2'-deoxy-l-nucleosides |
| EP1600452A3 (de) | 1999-11-12 | 2008-09-10 | Pharmasset, Inc. | Herstellung von 2'-Deoxy-L-Nukleoside |
| US6436948B1 (en) | 2000-03-03 | 2002-08-20 | University Of Georgia Research Foundation Inc. | Method for the treatment of psoriasis and genital warts |
| CA2308559C (en) | 2000-05-16 | 2005-07-26 | Brantford Chemicals Inc. | 1,3-oxathiolan-5-ones useful in the production of antiviral nucleoside analogues |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| KR20030036189A (ko) * | 2000-05-26 | 2003-05-09 | 이데닉스(케이만)리미티드 | 플라비바이러스 및 페스티바이러스의 치료방법 및 조성물 |
| US6787526B1 (en) | 2000-05-26 | 2004-09-07 | Idenix Pharmaceuticals, Inc. | Methods of treating hepatitis delta virus infection with β-L-2′-deoxy-nucleosides |
| US6875751B2 (en) * | 2000-06-15 | 2005-04-05 | Idenix Pharmaceuticals, Inc. | 3′-prodrugs of 2′-deoxy-β-L-nucleosides |
| US20030166606A1 (en) * | 2000-08-09 | 2003-09-04 | Kwan-Hee Kim | 5'-deoxy-n-(substituted oxycarbonyl)-5-fluorocytosine and derivatives thereof, method of preparing same, and anticancer composition comprising same as active ingredients |
| CN1446225A (zh) * | 2000-08-09 | 2003-10-01 | 可隆株式会社 | 5′－脱氧－n－(取代氧羰基)－5－氟胞嘧啶及其衍生物、制备方法,和包括该物质作为活性成分的抗癌组合物 |
| US20030228320A1 (en) * | 2000-08-18 | 2003-12-11 | Ashdown Martin Leonard | Retroviral immunotherapy |
| PT1411954E (pt) | 2000-10-18 | 2011-03-16 | Pharmasset Inc | Nucleosídeos modificados para o tratamento de infecções virais e proliferação celular anormal |
| DE10104231A1 (de) | 2001-01-31 | 2002-08-08 | Consortium Elektrochem Ind | Verfahren zur enzymatischen Herstellung von enantiomerenreinen 1,3-Dioxolan-4-on-Derivaten |
| CN102911166B (zh) * | 2001-03-01 | 2016-08-17 | 基利得科学公司 | 顺-ftc的多晶型物及其它晶型 |
| CA2380804A1 (en) * | 2001-05-01 | 2002-11-01 | Mitsui Chemicals, Inc. | Method for producing cytosine nucleosides compounds |
| CA2351049C (en) | 2001-06-18 | 2007-03-13 | Brantford Chemicals Inc. | Process for recovery of the desired cis-1,3-oxathiolane nucleosides from their undesired trans-isomers |
| ITMI20012317A1 (it) * | 2001-11-06 | 2003-05-06 | Recordati Ind Chimica E Farma | Processo diastereoselettivo per la preparazione del'agente antivirale4-amino-1-(2r-idrossimetil-/1,3/ossatiolan-5s-i1)-1h-pirimidin-2-one |
| BR0214940A (pt) * | 2001-12-14 | 2006-05-30 | Pharmasset Ltd | preparação de intermediários úteis na sìntese de nucleosìdeos antivirais |
| AUPS054702A0 (en) * | 2002-02-14 | 2002-03-07 | Immunaid Pty Ltd | Cancer therapy |
| US6897302B2 (en) * | 2002-04-12 | 2005-05-24 | Achillion Pharmaceuticals, Inc. | Method for synthesizing β-L-5-fluoro-2′,3′-dideoxy-2′,3′-didehydrocytidine (β-L-FD4C) |
| CN101172993A (zh) * | 2002-06-28 | 2008-05-07 | 埃迪尼克斯(开曼)有限公司 | 用于治疗黄病毒感染的2′－c－甲基－3′－o－l－缬氨酸酯核糖呋喃基胞苷 |
| AU2003248748A1 (en) * | 2002-06-28 | 2004-01-19 | Idenix (Cayman) Limited | 2'-c-methyl-3'-o-l-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
| US7608600B2 (en) * | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| TWI244393B (en) * | 2002-08-06 | 2005-12-01 | Idenix Pharmaceuticals Inc | Crystalline and amorphous forms of beta-L-2'-deoxythymidine |
| ATE496054T1 (de) | 2002-08-06 | 2011-02-15 | Pharmasset Inc | Verfahren zur herstellung von 1,3-dioxolan- nucleosiden |
| BR0314259A (pt) * | 2002-09-13 | 2005-07-26 | Idenix Cayman Ltd | ß-l-2'-desoxinucleosìdeos para o tratamento de cepas de hbv resistentes e terapias combinadas |
| KR20050088079A (ko) | 2002-11-15 | 2005-09-01 | 이데닉스 (케이만) 리미티드 | 2'-분지형 뉴클레오시드 및 플라비비리다에 돌연변이 |
| CN100406017C (zh) * | 2002-12-09 | 2008-07-30 | 佐治亚大学研究基金会 | 用于对抗hiv抗性株的二氧戊环基胸腺嘧啶及其组合物 |
| EP2319853B1 (de) * | 2002-12-12 | 2014-03-12 | IDENIX Pharmaceuticals, Inc. | Verfahren zur Herstellung von 2 -verzweigten Nucleosiden |
| ES2308136T3 (es) * | 2003-01-14 | 2008-12-01 | Gilead Sciences, Inc. | Composiciones y procedimientos para la politerapia antiviral. |
| AU2004224191A1 (en) | 2003-03-24 | 2004-10-07 | F. Hoffmann-La Roche Ag | Non-nucleoside reverse transcriptase inhibitors |
| ITMI20030578A1 (it) * | 2003-03-24 | 2004-09-25 | Clariant Lsm Italia Spa | Processo ed intermedi per la preparazione di emtricitabina |
| EP1639121A4 (de) * | 2003-06-30 | 2008-04-16 | Idenix Cayman Ltd | Synthese von beta-l-2-desoxynukleosiden |
| GB0317009D0 (en) | 2003-07-21 | 2003-08-27 | Univ Cardiff | Chemical compounds |
| CN1898569A (zh) | 2003-10-24 | 2007-01-17 | 伊缪因艾德有限公司 | 治疗方法 |
| WO2005074654A2 (en) * | 2004-02-03 | 2005-08-18 | Emory University | Methods to manufacture 1,3-dioxolane nucleosides |
| PT1778251E (pt) | 2004-07-27 | 2011-06-29 | Gilead Sciences Inc | Análogos de fosfonato de compostos inibidores de vih |
| JP4058057B2 (ja) * | 2005-04-26 | 2008-03-05 | 株式会社東芝 | 日中機械翻訳装置、日中機械翻訳方法および日中機械翻訳プログラム |
| 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 |
| KR20080056220A (ko) | 2005-10-19 | 2008-06-20 | 에프. 호프만-라 로슈 아게 | 페닐-아세트아마이드 ｎｎｒｔ 저해제 |
| US8076303B2 (en) | 2005-12-13 | 2011-12-13 | Spring Bank Pharmaceuticals, Inc. | Nucleotide and oligonucleotide prodrugs |
| US7781576B2 (en) * | 2005-12-23 | 2010-08-24 | Idenix Pharmaceuticals, Inc. | Process for preparing a synthetic intermediate for preparation of branched nucleosides |
| WO2007082890A1 (en) * | 2006-01-17 | 2007-07-26 | N.V. Organon | SELECTIVE ENZYMATIC HYDROLYSIS OF C-TERMINAL tert-BUTYL ESTERS OF PEPTIDES |
| US9044509B2 (en) * | 2006-02-03 | 2015-06-02 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Inhibition of HIV infection through chemoprophylaxis |
| US8895531B2 (en) * | 2006-03-23 | 2014-11-25 | Rfs Pharma Llc | 2′-fluoronucleoside phosphonates as antiviral agents |
| ES2357159T3 (es) * | 2006-04-18 | 2011-04-19 | Lupin Ltd. | Forma cristalina novedosa de lamivudina. |
| PT2487165T (pt) | 2006-07-07 | 2016-11-18 | Gilead Sciences Inc | Moduladores de propriedades farmacocinéticas de agentes terapêuticos |
| ES2550152T3 (es) | 2006-12-13 | 2015-11-04 | F. Hoffmann-La Roche Ag | Derivados de 2-(piperidin-4-il)-4-fenoxi-o fenilamino-pirimidina como inhibidores no nucleósidos de transcriptasa inversa |
| ES2601820T3 (es) | 2007-02-23 | 2017-02-16 | Gilead Sciences, Inc. | Moduladores de propiedades terapéutica de las farmacocinéticas |
| CN101307048B (zh) * | 2007-05-18 | 2011-03-23 | 上海迪赛诺医药发展有限公司 | 立体选择性制备拉米夫定的方法 |
| EP2159224B1 (de) | 2007-06-18 | 2012-08-01 | Sunshine Lake Pharma Co., Ltd | Bromphenylsubstituierte thiazolyldihydropyrimidine |
| EP2175863B1 (de) | 2007-07-09 | 2018-03-21 | Eastern Virginia Medical School | Substituierte nukleosidderivate mit antiviralen und antimikrobiellen eigenschaften |
| WO2009052050A1 (en) * | 2007-10-15 | 2009-04-23 | Pharmasset, Inc. | Dioxolane thymine phosphoramidates as anti-hiv agents |
| BRPI0820224A2 (pt) * | 2007-11-29 | 2015-06-16 | Ranbaxy Lab Ltd | Composto de fórmula iii ou seus estereoisômeros; processo para sua preparação e seu uso; uso de um composto de formula iii(a) ou iii(b) em um processo para a preparação de lamivudina de fórmula i(a) ou um composto de fórmula i(c); processo para preparação de lamivudina de fórmula i(a) |
| BRPI0820226A2 (pt) * | 2007-11-29 | 2015-06-16 | Ranbaxy Lab Ltd | Processo para o preparo de um 1,3-oxatiolana, para o preparo de lamivudina e para isolar lamivudina, lamivudina e composição farmacêutica |
| JPWO2009107692A1 (ja) | 2008-02-29 | 2011-07-07 | 株式会社カネカ | ２’−水酸基が保護されたリボヌクレオシド誘導体およびその製造方法 |
| EP2350065A1 (de) * | 2008-11-12 | 2011-08-03 | Lupin Ltd. | Neues polymorph von emtricitabin und verfahren zu dessen herstellung |
| TWI432436B (zh) | 2008-12-09 | 2014-04-01 | Gilead Sciences Inc | 類鐸受體的調節劑 |
| US20110282046A1 (en) | 2009-01-19 | 2011-11-17 | Rama Shankar | Process for preparation of cis-nucleoside derivative |
| KR101474570B1 (ko) | 2009-04-13 | 2014-12-19 | 주식회사 대희화학 | 라미부딘의 신규한 중간체 및 이의 제조방법 |
| ES2548508T3 (es) | 2009-05-27 | 2015-10-19 | Biotempus Limited | Métodos de tratamiento de enfermedades |
| US8710218B2 (en) | 2009-07-15 | 2014-04-29 | Lupin Limited | Process for preparation of Efavirenz |
| US20120295930A1 (en) | 2010-02-03 | 2012-11-22 | Shankar Rama | Novel process for the preparation of cis-nucleoside derivative |
| US20110223131A1 (en) | 2010-02-24 | 2011-09-15 | Gilead Sciences, Inc. | Antiviral compounds |
| WO2011141805A2 (en) | 2010-05-14 | 2011-11-17 | Lupin Limited | An improved process for the manufacture of lamivudine |
| EP2739620A1 (de) | 2011-08-05 | 2014-06-11 | Lupin Limited | Stereoselektives verfahren zur herstellung von 1,3-oxathiolan-nukleosiden |
| CN102584800A (zh) * | 2011-12-16 | 2012-07-18 | 四川大学 | 手性吲哚酮和当归内酯骨架化合物及不对称合成 |
| AU2013257951A1 (en) | 2012-05-11 | 2015-01-22 | Akron Molecules Ag | Use of compounds for the treatment of pain |
| NZ708177A (en) * | 2012-11-16 | 2017-08-25 | Univ College Cardiff Consultants Ltd | Process for preparing nucleoside prodrugs |
| MD4841B1 (ro) | 2012-12-21 | 2023-01-31 | Gilead Sciences, Inc. | Compuşi policiclici de carbamoilpiridonă şi utilizarea lor farmaceutică |
| NO2865735T3 (de) | 2013-07-12 | 2018-07-21 | ||
| EP3252058B1 (de) | 2013-07-12 | 2021-01-20 | Gilead Sciences, Inc. | Polycyclische carbamoylpyridonverbindungen und deren verwendung zur behandlung von hiv-infektionen |
| MX2016002560A (es) | 2013-08-29 | 2016-10-26 | Teva Pharma | Forma de dosificacion unitaria que comprende emtricitabina, tenofovir, darunavir y ritonavir y un comprimido monolitico que comprende darunavir y ritonavir. |
| EP3105238A4 (de) | 2014-02-13 | 2017-11-08 | Ligand Pharmaceuticals, Inc. | Organische verbindungen und deren verwendungen |
| WO2015155673A1 (en) | 2014-04-08 | 2015-10-15 | Teva Pharmaceutical Industries Ltd | Unit dosage form comprising emtricitabine, tenofovir, darunavir and ritonavir |
| TWI744723B (zh) | 2014-06-20 | 2021-11-01 | 美商基利科學股份有限公司 | 多環型胺甲醯基吡啶酮化合物之合成 |
| TW201613936A (en) | 2014-06-20 | 2016-04-16 | Gilead Sciences Inc | Crystalline forms of(2R,5S,13aR)-8-hydroxy-7,9-dioxo-n-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide |
| NO2717902T3 (de) | 2014-06-20 | 2018-06-23 | ||
| WO2016001907A1 (en) | 2014-07-02 | 2016-01-07 | Prendergast Patrick T | Mogroside iv and mogroside v as agonist/stimulator/un-blocking agent for toll-like receptor 4 and adjuvant for use in human/animal vaccine and to stimulate immunity against disease agents. |
| EP3164136A4 (de) | 2014-07-02 | 2018-04-04 | Ligand Pharmaceuticals, Inc. | Prodrug-verbindungen und verwendungen davon |
| EP3166607B1 (de) | 2014-07-11 | 2022-08-31 | Gilead Sciences, Inc. | Modulatoren von toll-like-rezeptoren zur behandlung von hiv |
| US9675632B2 (en) | 2014-08-26 | 2017-06-13 | Enanta Pharmaceuticals, Inc. | Nucleoside and nucleotide derivatives |
| TWI738321B (zh) | 2014-12-23 | 2021-09-01 | 美商基利科學股份有限公司 | 多環胺甲醯基吡啶酮化合物及其醫藥用途 |
| SG11201707905WA (en) | 2015-04-02 | 2017-10-30 | Gilead Sciences Inc | Polycyclic-carbamoylpyridone compounds and their pharmaceutical use |
| EP3349757A1 (de) | 2015-09-15 | 2018-07-25 | Gilead Sciences, Inc. | Modulatoren von toll-like-rezeptoren zur behandlung von hiv |
| GB201610327D0 (en) * | 2016-06-14 | 2016-07-27 | Univ Nelson Mandela Metropolitan | Process for producing Lamivudine and Entricitabine |
| WO2018178722A1 (en) * | 2017-03-31 | 2018-10-04 | The University Of Liverpool | Prodrug compositions |
| CN111788196A (zh) | 2018-01-09 | 2020-10-16 | 配体药物公司 | 缩醛化合物及其治疗用途 |
Family Cites Families (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4000137A (en) * | 1975-06-10 | 1976-12-28 | American Home Products Corporation | Antitumor derivatives of periodate-oxidized nucleosides |
| JPS5259171A (en) * | 1975-11-10 | 1977-05-16 | Asahi Chem Ind Co Ltd | Preparation of uracil derivatives |
| JPS6045196B2 (ja) * | 1976-08-09 | 1985-10-08 | 株式会社興人 | １−（２−テトラヒドロフリル）ウラシル類の製造方法 |
| JPS5668674A (en) * | 1979-11-08 | 1981-06-09 | Shionogi & Co Ltd | 5-fluorouracil derivative |
| JPS5738774A (en) * | 1980-08-19 | 1982-03-03 | Chugai Pharmaceut Co Ltd | Uracil derivative and its preparation |
| JPS5839672A (ja) * | 1981-09-03 | 1983-03-08 | Chugai Pharmaceut Co Ltd | ウラシル誘導体 |
| DE3481191D1 (de) * | 1983-07-20 | 1990-03-08 | Teijin Ltd | Antineoplastisches mittel. |
| DE3534979A1 (de) * | 1985-07-25 | 1987-01-29 | Licentia Gmbh | Netzgeraet |
| US4879277A (en) * | 1985-08-26 | 1989-11-07 | The United States Of America As Represented By The Department Of Health And Human Services | Antiviral compositions and methods |
| WO1987001284A1 (en) * | 1985-08-26 | 1987-03-12 | United States Of America, Represented By The Unite | Inhibition of in vitro infectivity and cytopathic effect of htlv-iii/lav by 2',3'-dideoxynosine, 2',3'-dideoxyguanosine, or 2',3'-dideoxyadenosine |
| GB2181128A (en) * | 1985-09-17 | 1987-04-15 | Wellcome Found | 3'-azidonucleosides |
| US4916122A (en) * | 1987-01-28 | 1990-04-10 | University Of Georgia Research Foundation, Inc. | 3'-Azido-2',3'-dideoxyuridine anti-retroviral composition |
| US4963533A (en) * | 1986-10-24 | 1990-10-16 | Stichting Rega Vzw (Rega) | Therapeutic application of dideoxycytidinene |
| WO1988007532A1 (en) * | 1987-03-24 | 1988-10-06 | Nycomed A.S. | 2',3' dideoxyribofuranoxide derivatives |
| US5185437A (en) * | 1987-04-09 | 1993-02-09 | Burroughs Wellcome Co. | Therapeutic nucleosides |
| US5011774A (en) * | 1987-07-17 | 1991-04-30 | Bristol-Myers Squibb Co. | Dideoxyinosine by enzymatic deamination of dideoxyadenosine |
| US5047407A (en) * | 1989-02-08 | 1991-09-10 | Iaf Biochem International, Inc. | 2-substituted-5-substituted-1,3-oxathiolanes with antiviral properties |
| 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 |
| US5466806A (en) * | 1989-02-08 | 1995-11-14 | 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 |
| US5270315A (en) * | 1988-04-11 | 1993-12-14 | Biochem Pharma Inc. | 4-(purinyl bases)-substituted-1,3-dioxlanes |
| US5684164A (en) * | 1988-04-11 | 1997-11-04 | Biochem Pharma Inc. | Processes for preparing substituted 1,3-oxathiolanes with antiviral properties |
| US4900828A (en) * | 1988-05-12 | 1990-02-13 | Hoffmann-Laroche Inc. | Intermediate compounds and an improved procedure for the synthesis of 2',3'-dideoxycytidine |
| CA1318627C (en) * | 1988-07-14 | 1993-06-01 | Jeffrey M. Howell | Enzymatic resolution process |
| US5106750A (en) * | 1988-08-30 | 1992-04-21 | G. D. Searle & Co. | Enantio- and regioselective synthesis of organic compounds using enol esters as irreversible transacylation reagents |
| JPH0269476A (ja) * | 1988-09-06 | 1990-03-08 | Kohjin Co Ltd | ピリミジン誘導体の製法 |
| JPH0269469A (ja) * | 1988-09-06 | 1990-03-08 | Kohjin Co Ltd | ジヒドロフラン誘導体及びその製法 |
| GB8822546D0 (en) * | 1988-09-26 | 1988-11-02 | Wellcome Found | Antiviral combinations |
| AU618436B2 (en) * | 1988-12-19 | 1991-12-19 | Wellcome Foundation Limited, The | Antiviral cytosine and guanine derivatives |
| HU226137B1 (en) * | 1989-02-08 | 2008-05-28 | Shire Canada Inc | Process for preparing substituted 1,3-oxathiolanes with antiviral properties |
| NZ233197A (en) * | 1989-04-13 | 1991-11-26 | Richard Thomas Walker | Aromatically substituted nucleotide derivatives, intermediates therefor and pharmaceutical compositions |
| US5059690A (en) * | 1990-03-01 | 1991-10-22 | E. R. Squibb & Sons, Inc. | Purinyl tetrahydrofurans |
| CA2023856A1 (en) * | 1989-09-26 | 1991-03-27 | Jeffrey M. Howell | Enzymatic resolution process |
| US5071983A (en) * | 1989-10-06 | 1991-12-10 | Burroughs Wellcome Co. | Therapeutic nucleosides |
| IE904378A1 (en) * | 1989-12-20 | 1991-07-03 | Abbott Lab | Analogs of oxetanyl purines and pyrimidines |
| 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 |
| 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 |
| US5204466A (en) * | 1990-02-01 | 1993-04-20 | Emory University | Method and compositions for the synthesis of bch-189 and related compounds |
| US5827727A (en) * | 1990-02-01 | 1998-10-27 | Emory University | Method of resolution of 1,3-oxathiolane nucleoside enantiomers |
| US5276151A (en) * | 1990-02-01 | 1994-01-04 | Emory University | Method of synthesis of 1,3-dioxolane nucleosides |
| US6703396B1 (en) * | 1990-02-01 | 2004-03-09 | Emory University | Method of resolution and antiviral activity of 1,3-oxathiolane nuclesoside enantiomers |
| GB9009861D0 (en) * | 1990-05-02 | 1990-06-27 | Glaxo Group Ltd | Chemical compounds |
| IT1246983B (it) * | 1990-11-13 | 1994-12-12 | Consiglio Nazionale Ricerche | L-2'-desossiuridine e composizioni farmaceutiche che le contengono. |
| US5587480A (en) * | 1990-11-13 | 1996-12-24 | Biochem Pharma, Inc. | Substituted 1,3-oxathiolanes and substituted 1,3-dithiolanes with antiviral properties |
| 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 |
| AU9125991A (en) * | 1990-12-05 | 1992-07-08 | University Of Georgia Research Foundation, Inc., The | Enantiomerically pure beta -l-(-)-1,3-oxathiolane nucleosides |
| US5444063A (en) * | 1990-12-05 | 1995-08-22 | Emory University | Enantiomerically pure β-D-dioxolane nucleosides with selective anti-Hepatitis B virus activity |
| US5248776A (en) * | 1990-12-05 | 1993-09-28 | University Of Georgia Research Foundation, Inc. | Process for enantiomerically pure β-L-1,3-oxathiolane 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 (- |
| IL100965A (en) * | 1991-02-22 | 1999-12-31 | Univ Emory | 2 - Hydroxymethyl - 5 -) 5 - Fluorocytocin - 1 - Eyal (- 1, 3 - Oxathiolane, its resolution and pharmaceuticals containing it |
| GB9104740D0 (en) * | 1991-03-06 | 1991-04-17 | Wellcome Found | Antiviral nucleoside combination |
| IL101144A (en) * | 1991-03-06 | 1996-09-12 | Wellcome Found | Pharmaceutical preparations containing 1 -) 2 -) hydroxymethyl (- 1, 3 - oxathiolan-5 - il (5) fluorescitosin and its derivatives for the treatment of their hepatitis B virus infections |
| 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 |
| GB9111902D0 (en) * | 1991-06-03 | 1991-07-24 | Glaxo Group Ltd | Chemical compounds |
| GB9116601D0 (en) * | 1991-08-01 | 1991-09-18 | Iaf Biochem Int | 1,3-oxathiolane nucleoside analogues |
| GB9307013D0 (en) * | 1993-04-02 | 1993-05-26 | Wellcome Found | Therapeutic combinations |
| SE510803C2 (sv) * | 1994-12-13 | 1999-06-28 | Volvo Ab | Tryckmediepåverkad manöveranordning |
| US5639787A (en) * | 1995-02-28 | 1997-06-17 | The Center For The Improvement Of Human Functioning Int'l, Inc. | Therapeutic method for the treatment of cancer |
-
1990
- 1990-02-01 US US07/473,318 patent/US5204466A/en not_active Expired - Fee Related
-
1991
- 1991-01-31 DK DK98201737T patent/DK0872237T3/da active
- 1991-01-31 HU HU922496Q patent/HU9202496D0/hu unknown
- 1991-01-31 HU HU9202496A patent/HU227485B1/hu unknown
- 1991-01-31 RU RU92016627A patent/RU2125558C1/ru active
- 1991-01-31 KR KR10-1999-7008970A patent/KR100381705B1/ko not_active IP Right Cessation
- 1991-01-31 AT AT91904454T patent/ATE170750T1/de active
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- 1991-01-31 HU HU922496A patent/HUT62566A/hu unknown
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- 1991-01-31 ES ES98201737T patent/ES2279559T3/es not_active Expired - Lifetime
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- 1991-01-31 EP EP06077328A patent/EP1772151A3/de not_active Withdrawn
- 1991-01-31 KR KR1019920701845A patent/KR100188357B1/ko not_active IP Right Cessation
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1992
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- 1992-07-30 FI FI923446A patent/FI114471B/fi active IP Right Grant
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1993
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1995
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1997
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1998
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1999
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2000
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2001
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2002
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2003
- 2003-06-24 FI FI20030933A patent/FI116222B/fi active IP Right Grant
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2004
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2005
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2006
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2008
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2010
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