NO313268B1 - Anvendelse av (2S,4S)-1-(2-hydroksymetyl-1,3-dioksolan-4- yl)cytosin for fremstilling av medikamenter for behandling avcancer - Google Patents
Anvendelse av (2S,4S)-1-(2-hydroksymetyl-1,3-dioksolan-4- yl)cytosin for fremstilling av medikamenter for behandling avcancer Download PDFInfo
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- NO313268B1 NO313268B1 NO19971015A NO971015A NO313268B1 NO 313268 B1 NO313268 B1 NO 313268B1 NO 19971015 A NO19971015 A NO 19971015A NO 971015 A NO971015 A NO 971015A NO 313268 B1 NO313268 B1 NO 313268B1
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- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
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- 231100000041 toxicology testing Toxicity 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
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 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
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- MJIBOYFUEIDNPI-HBNMXAOGSA-L zinc 5-[2,3-dihydroxy-5-[(2R,3R,4S,5R,6S)-4,5,6-tris[[3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoyl]oxy]-2-[[3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoyl]oxymethyl]oxan-3-yl]oxycarbonylphenoxy]carbonyl-3-hydroxybenzene-1,2-diolate Chemical class [Zn++].Oc1cc(cc(O)c1O)C(=O)Oc1cc(cc(O)c1O)C(=O)OC[C@H]1O[C@@H](OC(=O)c2cc(O)c(O)c(OC(=O)c3cc(O)c(O)c(O)c3)c2)[C@H](OC(=O)c2cc(O)c(O)c(OC(=O)c3cc(O)c(O)c(O)c3)c2)[C@@H](OC(=O)c2cc(O)c(O)c(OC(=O)c3cc(O)c(O)c(O)c3)c2)[C@@H]1OC(=O)c1cc(O)c(O)c(OC(=O)c2cc(O)c([O-])c([O-])c2)c1 MJIBOYFUEIDNPI-HBNMXAOGSA-L 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
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US08/301,298 US5817667A (en) | 1991-04-17 | 1994-09-06 | Compounds and methods for the treatment of cancer |
US39063395A | 1995-02-17 | 1995-02-17 | |
PCT/US1995/011464 WO1996007413A1 (en) | 1994-09-06 | 1995-09-05 | Compounds and methods for the treatment of cancer |
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NO971015L NO971015L (no) | 1997-03-05 |
NO971015D0 NO971015D0 (no) | 1997-03-05 |
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NO19971015A NO313268B1 (no) | 1994-09-06 | 1997-03-05 | Anvendelse av (2S,4S)-1-(2-hydroksymetyl-1,3-dioksolan-4- yl)cytosin for fremstilling av medikamenter for behandling avcancer |
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KR (1) | KR100374477B1 (ja) |
CN (3) | CN1827108A (ja) |
AP (1) | AP783A (ja) |
AT (1) | ATE267015T1 (ja) |
AU (1) | AU704977B2 (ja) |
BG (1) | BG63122B1 (ja) |
BR (1) | BR9508886A (ja) |
CA (1) | CA2199117C (ja) |
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ES (1) | ES2219666T3 (ja) |
FI (1) | FI970918A (ja) |
HU (1) | HUT77172A (ja) |
IL (1) | IL115156A (ja) |
IS (1) | IS2011B (ja) |
MY (1) | MY121548A (ja) |
NO (1) | NO313268B1 (ja) |
NZ (1) | NZ335013A (ja) |
OA (1) | OA10473A (ja) |
PL (2) | PL188359B1 (ja) |
PT (1) | PT781136E (ja) |
RO (1) | RO118748B1 (ja) |
RU (1) | RU2168995C2 (ja) |
SI (1) | SI0781136T1 (ja) |
SK (1) | SK284564B6 (ja) |
WO (1) | WO1996007413A1 (ja) |
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Families Citing this family (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6903224B2 (en) | 1988-04-11 | 2005-06-07 | Biochem Pharma Inc. | Substituted 1,3-oxathiolanes |
US6069252A (en) * | 1990-02-01 | 2000-05-30 | Emory University | Method of resolution and antiviral activity of 1,3-oxathiolane nucleoside enantiomers |
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 |
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 |
CN1307421C (zh) | 1997-08-08 | 2007-03-28 | 塞米得肿瘤学美国公司 | 克服生物及化学治疗抗性的方法与组合物 |
US7462605B2 (en) | 1998-01-23 | 2008-12-09 | Celmed Oncology (Usa), Inc. | Phosphoramidate compounds and methods of use |
DE69900841T2 (de) | 1998-01-23 | 2002-10-02 | Newbiotics Inc | Durch enzymkatalyse erhaltene therapeutische substanzen. |
BR9908270A (pt) | 1998-02-25 | 2004-06-29 | Univ Emory | 2-fluoro-nucleosìdeos, composições farmacêuticas e seus usos |
CA2366012A1 (en) * | 1999-03-29 | 2000-10-05 | Shire Biochem Inc. | Methods of treating leukemia |
AU2004201676B2 (en) * | 1999-03-29 | 2006-03-09 | University Of Georgia Research Foundation, Inc. | Methods of treating leukemia |
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 |
US6683061B1 (en) | 1999-07-22 | 2004-01-27 | Newbiotics, Inc. | Enzyme catalyzed therapeutic activation |
US6583149B1 (en) | 1999-09-24 | 2003-06-24 | Biochem Pharma Inc. | Method for the treatment or prevention of viral infection using nucleoside analogues |
US6566365B1 (en) | 1999-11-04 | 2003-05-20 | Biochem Pharma Inc. | Method for the treatment of Flaviviridea viral infection using nucleoside analogues |
EP1600452A3 (en) | 1999-11-12 | 2008-09-10 | Pharmasset, Inc. | Synthesis of 2'-deoxy-L-nucleosides |
PL361310A1 (en) * | 2000-10-13 | 2004-10-04 | Shire Biochem Inc. | Dioxolane analogs for improved inter-cellular delivery |
CA2441350A1 (en) | 2001-01-19 | 2002-07-25 | Newbiotics, Inc. | Methods to treat autoimmune and inflammatory conditions |
CN1744902B (zh) * | 2001-03-23 | 2010-05-26 | 希拉加拿大股份有限公司 | 治疗癌症的药物组合 |
DE60234577D1 (de) | 2001-03-23 | 2010-01-14 | Shire Canada Inc | Pharmazeutische mischung zur behandlung von krebs, die dioxolan nukleosidanalogen enthält |
US20030027799A1 (en) * | 2001-03-30 | 2003-02-06 | Shire Biochem Inc. | Methods of treating cancer using a combination of drugs |
AU2002336864B2 (en) * | 2001-11-02 | 2006-08-17 | Shire Biochem Inc. | Pharmaceutical compositions for the treatment of leukemia comprising dioxolane nucleosides analogs |
PT1448186E (pt) * | 2001-11-19 | 2009-03-24 | Medigene Ag | Medicamento para o tratamento de doenças virais da pele e doenças tumorais |
JP4299779B2 (ja) | 2002-06-21 | 2009-07-22 | エルジー エレクトロニクス インコーポレーテッド | ビデオデータの再生を管理するためのデータ構造を有する記録媒体 |
MXPA04002365A (es) | 2002-06-21 | 2004-11-22 | Lg Electronics Inc | Medio de grabacion que tiene estructura de datos para manejar la reproduccion de datos de video grabados en el mismo. |
KR20040000290A (ko) | 2002-06-24 | 2004-01-03 | 엘지전자 주식회사 | 고밀도 광디스크의 멀티 경로 데이터 스트림 관리방법 |
WO2004001751A1 (en) | 2002-06-24 | 2003-12-31 | Lg Electronics Inc. | Recording medium having data structure including navigation control information for managing reproduction of video data recorded thereon and recording and reproducing methods and apparatuses |
CA2459086C (en) | 2002-06-28 | 2013-08-13 | Lg Electronics Inc. | Recording medium having data structure for managing recording and reproduction of multiple path data recorded thereon and recording and reproducing methods and apparatus |
RU2347284C2 (ru) | 2002-10-14 | 2009-02-20 | Эл Джи Электроникс Инк. | Носитель записи со структурой данных для управления воспроизведением записанного на нем множества аудиопотоков и способы и устройства записи и воспроизведения |
CN100479051C (zh) | 2002-10-15 | 2009-04-15 | Lg电子有限公司 | 具有管理多路图形流重现的数据结构的记录介质及记录和重现方法和装置 |
US7720356B2 (en) | 2002-11-12 | 2010-05-18 | Lg Electronics Inc | Recording medium having data structure for managing reproduction of multiple reproduction path video data recorded thereon and recording and reproducing methods and apparatuses |
US7664372B2 (en) | 2002-11-20 | 2010-02-16 | Lg Electronics Inc. | Recording medium having data structure for managing reproduction of multiple component data recorded thereon and recording and reproducing methods and apparatuses |
US7693394B2 (en) | 2003-02-26 | 2010-04-06 | Lg Electronics Inc. | Recording medium having data structure for managing reproduction of data streams recorded thereon and recording and reproducing methods and apparatuses |
US7809775B2 (en) | 2003-02-27 | 2010-10-05 | Lg Electronics, Inc. | Recording medium having data structure for managing playback control recorded thereon and recording and reproducing methods and apparatuses |
EP1604356A4 (en) | 2003-02-28 | 2009-12-16 | Lg Electronics Inc | RECORD MEDIUM WITH A DATA STRUCTURE FOR MANAGING THE RANDOM / SHUFFLE PLAYBACK OF RECORDED VIDEO DATA, AND METHOD AND DEVICES FOR RECORDING AND PLAYING |
US7620301B2 (en) | 2003-04-04 | 2009-11-17 | Lg Electronics Inc. | System and method for resuming playback |
AU2004281525B2 (en) | 2003-10-09 | 2010-01-28 | Aresus Pharma GmbH | The use of a polyphenol for the treatment of a cancerous or pre-cancerous lesion of the skin |
CN103735560A (zh) | 2005-06-07 | 2014-04-23 | 耶鲁大学 | 使用克来夫定和替比夫定治疗癌症和其它病症或疾病状态的方法 |
US7951788B2 (en) * | 2005-12-02 | 2011-05-31 | Yale University | Method of treating cancer and other conditions or disease states using L-cytosine nucleoside analogs |
NO324263B1 (no) | 2005-12-08 | 2007-09-17 | Clavis Pharma Asa | Kjemiske forbindelser, anvendelse derav ved behandling av kreft, samt farmasoytiske preparater som omfatter slike forbindelser |
CN101534835B (zh) * | 2006-09-01 | 2012-05-30 | 佐治亚大学研究基金会 | 用于癌症的L-OddC的前药 |
CN102406649A (zh) * | 2011-11-15 | 2012-04-11 | 张始状 | 人体五种正常碱基在制备治疗肿瘤药物中的应用 |
CN103720693A (zh) * | 2011-11-15 | 2014-04-16 | 张始状 | 人体五种正常碱基在制备治疗肿瘤药物中的应用 |
SG10201609131YA (en) | 2016-11-01 | 2018-06-28 | Xylonix Ip Holdings Pte Ltd | Zinc-pga compositions and methods for treating cancer |
CN110168092A (zh) * | 2016-12-28 | 2019-08-23 | 特朗斯吉有限公司 | 溶瘤病毒和治疗分子 |
SG10201708886RA (en) * | 2017-10-30 | 2019-05-30 | Xylonix Ip Holdings Pte Ltd | α-PGA-ZINC COMPOSITIONS AND METHODS FOR TREATING CANCER |
Family Cites Families (52)
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 |
JPS5668674A (en) * | 1979-11-08 | 1981-06-09 | Shionogi & Co Ltd | 5-fluorouracil derivative |
EP0206497B1 (en) * | 1985-05-15 | 1994-07-20 | The Wellcome Foundation Limited | Therapeutic nucleosides and their preparation |
JPS62501712A (ja) * | 1985-08-26 | 1987-07-09 | アメリカ合衆国 | 2′、3′―ジデオキシイノシン、2′,3′―ジデオキシグアノシンまたは2′,3′―ジデオキシアデノシンを含有する抗htlv―3/lav剤 |
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 |
DK167377B1 (da) * | 1985-09-17 | 1993-10-25 | Wellcome Found | 3'-azidopyrimidinnucleosider eller farmaceutisk acceptable salte eller estere deraf til anvendelse ved behandling af eller profylakse for en human retrovirusinfektion |
IN164556B (ja) * | 1986-03-06 | 1989-04-08 | Takeda Chemical Industries Ltd | |
US4916122A (en) * | 1987-01-28 | 1990-04-10 | University Of Georgia Research Foundation, Inc. | 3'-Azido-2',3'-dideoxyuridine anti-retroviral composition |
FR2601385B1 (fr) * | 1986-07-09 | 1989-09-29 | Sucre Rech & Dev | Procede de preparation a partir de saccharose d'un melange de sucres a haute teneur en isomaltose par voie enzymatique et produits obtenus |
US4963533A (en) * | 1986-10-24 | 1990-10-16 | Stichting Rega Vzw (Rega) | Therapeutic application of dideoxycytidinene |
US5215971A (en) * | 1986-12-19 | 1993-06-01 | Medivir Ab | Antiviral pharmaceutical composition comprising 5-substituted pyrimidine nucleosides |
NZ223990A (en) * | 1987-03-24 | 1990-08-28 | Nycomed As | Acylated 2',3'-dideoxynucleosides and pharmaceutical compositions |
US5185437A (en) * | 1987-04-09 | 1993-02-09 | Burroughs Wellcome Co. | Therapeutic nucleosides |
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 |
US5270315A (en) * | 1988-04-11 | 1993-12-14 | Biochem Pharma Inc. | 4-(purinyl bases)-substituted-1,3-dioxlanes |
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 |
US5466806A (en) * | 1989-02-08 | 1995-11-14 | Biochem Pharma Inc. | Processes for preparing substituted 1,3-oxathiolanes 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 |
US4900828A (en) * | 1988-05-12 | 1990-02-13 | Hoffmann-Laroche Inc. | Intermediate compounds and an improved procedure for the synthesis of 2',3'-dideoxycytidine |
SE8802687D0 (sv) * | 1988-07-20 | 1988-07-20 | Astra Ab | Nucleoside derivatives |
EP0375329B1 (en) * | 1988-12-19 | 1995-05-31 | The Wellcome Foundation Limited | Antiviral pyrimidine and purine compounds, process for their preparation and pharmaceutical compositions containing them |
UA45942A (uk) * | 1989-02-08 | 2002-05-15 | Біокем Фарма, Інк. | 1,3-оксатіолан, його похідні, спосіб (варіанти) його одержання та фармацевтична композиція |
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 |
US5071983A (en) * | 1989-10-06 | 1991-12-10 | Burroughs Wellcome Co. | Therapeutic nucleosides |
US5350836A (en) * | 1989-10-12 | 1994-09-27 | Ohio University | Growth hormone antagonists |
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 |
US5204466A (en) * | 1990-02-01 | 1993-04-20 | Emory University | Method and compositions for the synthesis of bch-189 and related compounds |
US5276151A (en) * | 1990-02-01 | 1994-01-04 | Emory University | Method of synthesis of 1,3-dioxolane nucleosides |
US5527782A (en) * | 1990-03-13 | 1996-06-18 | Acic (Canada) Inc. | 5-halo-2,3'-O-cyclocytidines |
GB9009861D0 (en) * | 1990-05-02 | 1990-06-27 | Glaxo Group Ltd | Chemical compounds |
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 |
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 |
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 (- |
NZ250842A (en) * | 1991-02-22 | 1996-03-26 | Univ Emory | Resolution of a racemic mixture of nucleoside enantiomers such as 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane (ftc) |
GB9104740D0 (en) * | 1991-03-06 | 1991-04-17 | Wellcome Found | Antiviral nucleoside combination |
SK279542B6 (sk) * | 1991-03-06 | 1998-12-02 | The Wellcome Foundation Limited | U |
US5817667A (en) * | 1991-04-17 | 1998-10-06 | University Of Georgia Research Foudation | Compounds and methods for the treatment of cancer |
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 |
GB9226927D0 (en) | 1992-12-24 | 1993-02-17 | Iaf Biochem Int | Dideoxy nucleoside analogues |
US5627160A (en) * | 1993-05-25 | 1997-05-06 | Yale University | L-2',3'-dideoxy nucleoside analogs as anti-hepatitis B (HBV) and anti-HIV agents |
WO1995018137A1 (en) * | 1993-12-30 | 1995-07-06 | Genta Incorporated | Improved process for the purification of oligomers |
US5587362A (en) * | 1994-01-28 | 1996-12-24 | Univ. Of Ga Research Foundation | L-nucleosides |
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 |
US5971983A (en) * | 1997-05-09 | 1999-10-26 | The Regents Of The University Of California | Tissue ablation device and method of use |
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