CS246075B2 - Method of 2,2-difluoronucleoside production - Google Patents
Method of 2,2-difluoronucleoside production Download PDFInfo
- Publication number
- CS246075B2 CS246075B2 CS841667A CS166784A CS246075B2 CS 246075 B2 CS246075 B2 CS 246075B2 CS 841667 A CS841667 A CS 841667A CS 166784 A CS166784 A CS 166784A CS 246075 B2 CS246075 B2 CS 246075B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- desoxy
- bis
- evaporated
- mixture
- solution
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 238000000034 method Methods 0.000 title description 16
- 150000001875 compounds Chemical class 0.000 claims description 35
- 125000006239 protecting group Chemical group 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000002777 nucleoside Substances 0.000 abstract description 16
- 125000003835 nucleoside group Chemical group 0.000 abstract description 10
- 238000002360 preparation method Methods 0.000 abstract description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- -1 acyclic nucleoside Chemical class 0.000 description 64
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 239000000203 mixture Substances 0.000 description 41
- 239000000243 solution Substances 0.000 description 40
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- 238000006243 chemical reaction Methods 0.000 description 28
- 239000000047 product Substances 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000000706 filtrate Substances 0.000 description 18
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
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- 239000002585 base Substances 0.000 description 14
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
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- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
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- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
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- DRNUNECHVNIYHQ-UHFFFAOYSA-N trimethyl-(5-methyl-2-trimethylsilyloxypyrimidin-4-yl)oxysilane Chemical compound CC1=CN=C(O[Si](C)(C)C)N=C1O[Si](C)(C)C DRNUNECHVNIYHQ-UHFFFAOYSA-N 0.000 description 3
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- DNLXUUDWPMFJMN-UHFFFAOYSA-N trimethylsilyl difluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)F DNLXUUDWPMFJMN-UHFFFAOYSA-N 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical class OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- 150000003751 zinc Chemical class 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
- C07H19/06—Pyrimidine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H11/00—Compounds containing saccharide radicals esterified by inorganic acids; Metal salts thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
-
- 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)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/473,883 US4526988A (en) | 1983-03-10 | 1983-03-10 | Difluoro antivirals and intermediate therefor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS246075B2 true CS246075B2 (en) | 1986-10-16 |
Family
ID=23881409
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS841667A CS246075B2 (en) | 1983-03-10 | 1984-03-08 | Method of 2,2-difluoronucleoside production |
Country Status (36)
| Country | Link |
|---|---|
| US (5) | US4526988A (OSRAM) |
| EP (1) | EP0122707B1 (OSRAM) |
| JP (2) | JPS59175498A (OSRAM) |
| KR (1) | KR860001283B1 (OSRAM) |
| AR (1) | AR243533A1 (OSRAM) |
| AT (1) | ATE29726T1 (OSRAM) |
| AU (1) | AU565856B2 (OSRAM) |
| BG (1) | BG40814A3 (OSRAM) |
| CA (2) | CA1218647A (OSRAM) |
| CS (1) | CS246075B2 (OSRAM) |
| CY (1) | CY1489A (OSRAM) |
| DD (1) | DD216468A5 (OSRAM) |
| DE (2) | DE3466224D1 (OSRAM) |
| DK (2) | DK162529C (OSRAM) |
| ES (1) | ES530364A0 (OSRAM) |
| FI (1) | FI77870C (OSRAM) |
| GB (2) | GB2136425B (OSRAM) |
| GR (1) | GR81845B (OSRAM) |
| HK (1) | HK44989A (OSRAM) |
| HU (1) | HU193893B (OSRAM) |
| IE (1) | IE57071B1 (OSRAM) |
| IL (2) | IL71143A (OSRAM) |
| KE (1) | KE3874A (OSRAM) |
| LU (1) | LU88791I2 (OSRAM) |
| MX (1) | MX9203246A (OSRAM) |
| MY (1) | MY102025A (OSRAM) |
| NL (1) | NL950018I2 (OSRAM) |
| NZ (1) | NZ207358A (OSRAM) |
| PH (2) | PH23240A (OSRAM) |
| PL (1) | PL142437B1 (OSRAM) |
| PT (1) | PT78181B (OSRAM) |
| RO (1) | RO89963A (OSRAM) |
| SG (1) | SG21889G (OSRAM) |
| SU (1) | SU1442076A3 (OSRAM) |
| UA (1) | UA5955A1 (OSRAM) |
| ZA (1) | ZA841605B (OSRAM) |
Families Citing this family (245)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4526988A (en) * | 1983-03-10 | 1985-07-02 | Eli Lilly And Company | Difluoro antivirals and intermediate therefor |
| DE3587500T2 (de) * | 1984-12-04 | 1993-12-16 | Lilly Co Eli | Tumorbehandlung bei Säugetieren. |
| ZA859008B (en) * | 1984-12-04 | 1987-07-29 | Lilly Co Eli | The treatment of tumors in mammals |
| US4681873A (en) * | 1985-07-29 | 1987-07-21 | Warner-Lambert Company | 4-amino-3-halo-2-pyridinone nucleoside and nucleotide compounds |
| CA1295998C (en) * | 1985-07-29 | 1992-02-18 | Sai P. Sunkara | Nucleosides and their use as antineoplastic agents |
| PT86377B (pt) * | 1986-12-24 | 1990-11-20 | Lilly Co Eli | Processo para a preparacao de conjugados de imunoglobulinas com um difluoronucleosideo acilado |
| US4814438A (en) * | 1986-12-24 | 1989-03-21 | Eli Lilly And Company | Immunoglobulin conjugates of 2',2'-difluronucleosides |
| US4994558A (en) * | 1986-12-24 | 1991-02-19 | Eli Lilly And Company | Immunoglobulin conjugates |
| EP0277599A3 (en) * | 1987-01-30 | 1990-05-09 | Asahi Glass Company Ltd. | Fluorine containing cyclopentane derivatives and processes for their production |
| CA1340645C (en) * | 1987-04-17 | 1999-07-13 | Victor E. Marquez | Acid stable dideoxynucleosides active against the cytopathic effects of human immunodeficiency virus |
| US5223608A (en) * | 1987-08-28 | 1993-06-29 | Eli Lilly And Company | Process for and intermediates of 2',2'-difluoronucleosides |
| US4965374A (en) * | 1987-08-28 | 1990-10-23 | Eli Lilly And Company | Process for and intermediates of 2',2'-difluoronucleosides |
| ATE217009T1 (de) * | 1987-08-28 | 2002-05-15 | Lilly Co Eli | Stereoselektives verfahren zur herstellung von geschützten 2',2'-difluorlactonen |
| US4914028A (en) * | 1988-02-10 | 1990-04-03 | Eli Lilly And Company | Method of preparing beta-2',2'-difluoronucleosides |
| US4983724A (en) * | 1988-02-16 | 1991-01-08 | Eli Lilly And Company | Inversion of 2,2-difluororibose to a 2,2-difluoroxylose and intermediates therefor |
| US5644043A (en) * | 1988-02-16 | 1997-07-01 | Eli Lilly And Company | 2',3'-dideoxy-2',2'-difluoronucleosides and intermediates |
| DE68923387T2 (de) * | 1988-02-16 | 1996-01-25 | Lilly Co Eli | 2',3'-Dideoxy-2',2'-difluornucleoside. |
| WO1989008658A1 (en) * | 1988-03-16 | 1989-09-21 | Scripps Clinic And Research Foundation | Substituted adenine derivatives useful as therapeutic agents |
| US5057301A (en) * | 1988-04-06 | 1991-10-15 | Neorx Corporation | Modified cellular substrates used as linkers for increased cell retention of diagnostic and therapeutic agents |
| JPH0232093A (ja) * | 1988-06-08 | 1990-02-01 | Merrell Dow Pharmaceut Inc | 抗レトロウィルスジフルオロ化ヌクレオシド類 |
| US4987224A (en) * | 1988-08-02 | 1991-01-22 | University Of Georgia Research Foundation, Inc. | Method of preparation of 2',3'-dideoxynucleosides |
| US5157114A (en) * | 1988-08-19 | 1992-10-20 | Burroughs Wellcome Co. | 2',3'-dideoxy-3'-fluoro-5-ethyngluridine |
| CA2012129A1 (en) * | 1989-03-20 | 1990-09-20 | Ramakrishnan Nagarajan | Recovery of difluoro sugar |
| US4954623A (en) * | 1989-03-20 | 1990-09-04 | Eli Lilly And Company | Recovery of difluoro sugar |
| US5426183A (en) * | 1992-06-22 | 1995-06-20 | Eli Lilly And Company | Catalytic stereoselective glycosylation process for preparing 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides |
| US5371210A (en) * | 1992-06-22 | 1994-12-06 | Eli Lilly And Company | Stereoselective fusion glycosylation process for preparing 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides |
| US5821357A (en) * | 1992-06-22 | 1998-10-13 | Eli Lilly And Company | Stereoselective glycosylation process for preparing 2'-deoxy-2',2'-difluoropurine and triazole nucleosides |
| US5594124A (en) * | 1992-06-22 | 1997-01-14 | Eli Lilly And Company | Stereoselective glycosylation process for preparing 2'-Deoxy-2',2'-difluoropyrimidine nucleosides and 2'-deoxy-2'-fluoropyrimidine nucleosides and intermediates thereof |
| CA2098887C (en) * | 1992-06-22 | 2003-10-28 | Ta-Sen Chou | Process for preparing alpha-anomer enriched 1-halo-2-deoxy-2,2-difluoro-d-ribofuranosyl derivatives |
| NO932286L (no) * | 1992-06-22 | 1993-12-23 | Lilly Co Eli | Stereoselektiv anion-glykosyleringsprosess |
| US5401861A (en) * | 1992-06-22 | 1995-03-28 | Eli Lilly And Company | Low temperature process for preparing alpha-anomer enriched 2-deoxy-2,2-difluoro-D-ribofuranosyl sulfonates |
| US5256797A (en) * | 1992-06-22 | 1993-10-26 | Eli Lilly And Company | Process for separating 2-deoxy-2,2-difluoro-D-ribofuranosyl alkylsulfonate anomers |
| US5252756A (en) * | 1992-06-22 | 1993-10-12 | Eli Lilly And Company | Process for preparing beta-anomer enriched 2-deoxy-2,2-difluoro-D-ribofuranosyl-arylsulfonates |
| US5606048A (en) * | 1992-06-22 | 1997-02-25 | Eli Lilly And Company | Stereoselective glycosylation process for preparing 2'-Deoxy-2', 2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides |
| US5256798A (en) * | 1992-06-22 | 1993-10-26 | Eli Lilly And Company | Process for preparing alpha-anomer enriched 2-deoxy-2,2-difluoro-D-ribofuranosyl sulfonates |
| YU43193A (sh) * | 1992-06-22 | 1997-01-08 | Eli Lilly And Company | 2'-deoksi-2',2'-difluoro(4-supstituisani)pirimidinski nukleozidi antivirusnog i antikancerogenog dejstva i međuproizvodi |
| US5401838A (en) * | 1992-06-22 | 1995-03-28 | Eli Lilly And Company | Stereoselective fusion glycosylation process for preparing 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides |
| US5424416A (en) * | 1993-08-25 | 1995-06-13 | Eli Lilly And Company | Process for preparation of 2-deoxy-2,2-difluoro-D-ribofuranosyl-3,5-hydroxy protected-1-alkyl and aryl sulfonates and their use in preparation of 2',2'-difluoro-2'-deoxy nucleosides |
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| US5428176A (en) * | 1994-04-14 | 1995-06-27 | Eli Lilly And Company | Process for preparing 2,2-difluoroketene silyl O,S-acetals and α,α-difluoro-β-silyloxy-1,3-dioxolane-4-propanoic acid O,S-esters |
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| US5559222A (en) * | 1995-02-03 | 1996-09-24 | Eli Lilly And Company | Preparation of 1-(2'-deoxy-2',2'-difluoro-D-ribo-pentofuranosyl)-cytosine from 2-deoxy-2,2-difluoro-β-D-ribo-pentopyranose |
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| US7435755B2 (en) * | 2000-11-28 | 2008-10-14 | The Trustees Of Dartmouth College | CDDO-compounds and combination therapies thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US2359208A (en) * | 1941-03-21 | 1944-09-26 | Lilly Co Eli | beta-substituted-delta alpha,beta-gamma-butyrolactones and beta-substituted-beta-hydroxy-gamma-butyrolactones and the methods of preparing them |
| US2359096A (en) * | 1941-03-21 | 1944-09-26 | Lilly Co Eli | beta-substituted-delta alpha, beta-gamma-butyrolactones and beta-substituted - beta - hydroxy-gamma-butyrolactones and methods of preparing them |
| FR1362039A (fr) * | 1963-04-17 | 1964-05-29 | Ct D Etudes Experimentales Et | Nouveau procédé de préparation du semi-aldéhyde succinique |
| US3282921A (en) * | 1964-06-04 | 1966-11-01 | Syntex Corp | Halo-deoxynucleosides and processes for the preparation thereof |
| US3870700A (en) * | 1973-05-29 | 1975-03-11 | Miles Lab | 2-halogeno-2-deoxy-5-(substituted)uridines |
| US4211773A (en) * | 1978-10-02 | 1980-07-08 | Sloan Kettering Institute For Cancer Research | 5-Substituted 1-(2'-Deoxy-2'-substituted-β-D-arabinofuranosyl)pyrimidine nucleosides |
| US4352795A (en) * | 1981-01-29 | 1982-10-05 | Warner-Lambert Company | 7-β-D-Arabinofuranosyl-7H-pyrrolo[2,3-d]pyrimidine compounds and methods for their production |
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| US4526988A (en) * | 1983-03-10 | 1985-07-02 | Eli Lilly And Company | Difluoro antivirals and intermediate therefor |
| US4625020A (en) * | 1983-11-18 | 1986-11-25 | Bristol-Myers Company | Nucleoside process |
| CA1295998C (en) * | 1985-07-29 | 1992-02-18 | Sai P. Sunkara | Nucleosides and their use as antineoplastic agents |
-
1983
- 1983-03-10 US US06/473,883 patent/US4526988A/en not_active Expired - Lifetime
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1984
- 1984-02-28 DK DK114484A patent/DK162529C/da not_active IP Right Cessation
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- 1984-03-02 CA CA000448698A patent/CA1218647A/en not_active Expired
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- 1984-03-04 IL IL71143A patent/IL71143A/xx not_active IP Right Cessation
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- 1984-03-06 GR GR74000A patent/GR81845B/el unknown
- 1984-03-06 EP EP84301463A patent/EP0122707B1/en not_active Expired
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- 1984-03-06 DE DE8484301463T patent/DE3466224D1/de not_active Expired
- 1984-03-06 DE DE1996175003 patent/DE19675003I2/de active Active
- 1984-03-06 LU LU88791C patent/LU88791I2/fr unknown
- 1984-03-06 GB GB08405805A patent/GB2136425B/en not_active Expired
- 1984-03-06 AT AT84301463T patent/ATE29726T1/de active
- 1984-03-07 ES ES530364A patent/ES530364A0/es active Granted
- 1984-03-07 AU AU25374/84A patent/AU565856B2/en not_active Expired
- 1984-03-07 SU SU843710351A patent/SU1442076A3/ru active
- 1984-03-07 UA UA3710351A patent/UA5955A1/uk unknown
- 1984-03-07 AR AR84295933A patent/AR243533A1/es active
- 1984-03-08 DD DD84260703A patent/DD216468A5/de unknown
- 1984-03-08 CS CS841667A patent/CS246075B2/cs unknown
- 1984-03-09 KR KR1019840001206A patent/KR860001283B1/ko not_active Expired
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- 1984-03-09 IE IE584/84A patent/IE57071B1/en not_active IP Right Cessation
- 1984-03-09 BG BG064592A patent/BG40814A3/xx unknown
- 1984-03-09 HU HU84963A patent/HU193893B/hu unknown
- 1984-03-09 JP JP59046387A patent/JPS59175498A/ja active Granted
- 1984-12-04 US US06/677,146 patent/US4692434A/en not_active Expired - Lifetime
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1986
- 1986-05-01 GB GB08610648A patent/GB2172287B/en not_active Expired
- 1986-05-14 CA CA000509195A patent/CA1223869A/en not_active Expired
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1987
- 1987-06-04 US US07/058,219 patent/US4808614A/en not_active Expired - Lifetime
- 1987-09-22 MY MYPI87001856A patent/MY102025A/en unknown
- 1987-10-26 PH PH35983A patent/PH23593A/en unknown
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1989
- 1989-04-08 SG SG218/89A patent/SG21889G/en unknown
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- 1989-06-01 HK HK449/89A patent/HK44989A/en not_active IP Right Cessation
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1990
- 1990-08-10 DK DK190590A patent/DK170647B1/da not_active IP Right Cessation
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1991
- 1991-02-07 US US07/652,349 patent/US5118820A/en not_active Expired - Lifetime
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1992
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1993
- 1993-01-14 JP JP5004752A patent/JPH06102655B2/ja not_active Expired - Lifetime
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1995
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