KR20050059975A - β-2'- 또는 3'-할로뉴클레오시드 - Google Patents
β-2'- 또는 3'-할로뉴클레오시드 Download PDFInfo
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- KR20050059975A KR20050059975A KR1020037016775A KR20037016775A KR20050059975A KR 20050059975 A KR20050059975 A KR 20050059975A KR 1020037016775 A KR1020037016775 A KR 1020037016775A KR 20037016775 A KR20037016775 A KR 20037016775A KR 20050059975 A KR20050059975 A KR 20050059975A
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- South Korea
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- compound
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- alkyl
- aryl
- alkoxyalkyl
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Classifications
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- 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
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- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
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- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
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- A—HUMAN NECESSITIES
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- 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
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- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H9/00—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical
- C07H9/02—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical the hetero ring containing only oxygen as ring hetero atoms
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| YU92202A (sh) | 2000-05-26 | 2006-01-16 | Idenix (Cayman) Limited | Metode i smeše za lečenje flavi virusa i pesti virusa |
| JP2004533805A (ja) * | 2000-10-18 | 2004-11-11 | フアーマセツト・リミテツド | 疾患細胞中の核酸の多重定量 |
| US8481712B2 (en) | 2001-01-22 | 2013-07-09 | Merck Sharp & Dohme Corp. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| US7105499B2 (en) | 2001-01-22 | 2006-09-12 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| CN1267446C (zh) | 2001-01-22 | 2006-08-02 | 默克公司 | 作为依赖于rna的rna病毒聚合酶的抑制剂的核苷衍生物 |
| CA2464031A1 (en) | 2001-10-30 | 2003-05-08 | Conforma Therapeutics Corporation | Purine analogs having hsp90-inhibiting activity |
| US7608600B2 (en) * | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| NZ537662A (en) | 2002-06-28 | 2007-10-26 | Idenix Cayman Ltd | 2'-C-methyl-3'-O-L-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
| 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 |
| US7138402B2 (en) | 2003-09-18 | 2006-11-21 | Conforma Therapeutics Corporation | Pyrrolopyrimidines and related analogs as HSP90-inhibitors |
| PT1576138T (pt) | 2002-11-15 | 2017-05-03 | Idenix Pharmaceuticals Llc | 2'-metil-nucleósidos em combinação com interferão e mutação de flaviviridae |
| RU2005121904A (ru) | 2002-12-12 | 2006-01-20 | Айденикс (Кайман) Лимитед (Ky) | Способ получения 2`-разветвленных нуклеозидов |
| WO2004087169A1 (en) * | 2003-03-27 | 2004-10-14 | Boehringer Ingelheim International Gmbh | Antiviral combination of nevirapine and a further antiretroviral compound |
| SI2604620T2 (sl) | 2003-05-30 | 2024-10-30 | Gilead Pharmasset Llc | Modificirani fluorirani nukleozidni analogi |
| JP2005289964A (ja) * | 2004-03-12 | 2005-10-20 | Ajinomoto Co Inc | ２−デオキシ−ｌ−リボース化合物の製造方法 |
| GB0505781D0 (en) * | 2005-03-21 | 2005-04-27 | Univ Cardiff | Chemical compounds |
| JP2008534609A (ja) | 2005-03-30 | 2008-08-28 | コンフォーマ・セラピューティクス・コーポレイション | Ｈｓｐ９０阻害剤としてのアルキニルピロロピリミジンおよび関連類似体 |
| JP2009510075A (ja) * | 2005-09-26 | 2009-03-12 | ファーマセット，インコーポレイティド | 抗ウイルス剤としての修飾４’−ヌクレオシド |
| WO2007075876A2 (en) | 2005-12-23 | 2007-07-05 | Idenix Pharmaceuticals, Inc. | Process for preparing a synthetic intermediate for preparation of branched nucleosides |
| MX2010000424A (es) * | 2007-07-09 | 2010-08-10 | Easter Virginia Medical School | Derivados de nucleosidos sustituidos con propiedades antivirales y antimicrobianas. |
| WO2012142075A1 (en) | 2011-04-13 | 2012-10-18 | Merck Sharp & Dohme Corp. | 2'-azido substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
| JP2014511875A (ja) | 2011-04-13 | 2014-05-19 | メルク・シャープ・アンド・ドーム・コーポレーション | ２’−シアノ置換ヌクレオシド誘導体およびウイルス疾患の治療のためのその使用方法 |
| EA201391519A1 (ru) | 2011-04-13 | 2014-03-31 | Мерк Шарп И Доум Корп. | 2'-замещенные нуклеозидные производные и способы их применения для лечения вирусных заболеваний |
| EP2731433A4 (en) | 2011-07-13 | 2014-12-31 | Merck Sharp & Dohme | 5'-SUBSTITUTED NUCLEOSIDE ANALOGA AND METHOD FOR THEIR USE FOR THE TREATMENT OF VIRUS DISEASES |
| WO2013009735A1 (en) | 2011-07-13 | 2013-01-17 | Merck Sharp & Dohme Corp. | 5'-substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
| BR112014019897A8 (pt) | 2012-02-14 | 2017-07-11 | Univ Georgia | Espiro[2.4]heptanos para tratamento de infecções por flaviviridae |
| JP5833225B2 (ja) | 2012-03-28 | 2015-12-16 | 富士フイルム株式会社 | １−（２−デオキシ−２−フルオロ−４−チオ−β−Ｄ−アラビノフラノシル）シトシンの塩 |
| DK2883866T3 (da) | 2012-08-13 | 2019-05-13 | Fujifilm Corp | MELLEMPRODUKT TIL SYNTESE AF 1-(2-DEOXY-2-FLUOR-4-THIO-beta-D- ARABINOFURANOSYL)CYTOSIN, MELLEMPRODUKT TIL SYNTESE AF THIONUKLEOSID OG FREMGANGSMÅDER TIL FREMSTILLING AF DISSE MELLEMPRODUKTER |
| EP3109245B1 (en) * | 2014-02-18 | 2018-01-03 | FUJIFILM Corporation | Method for producting thiolane skeleton-type glycoconjugate, and thiolane skeleton-type glycoconjugate |
| JP6204223B2 (ja) | 2014-02-19 | 2017-09-27 | 富士フイルム株式会社 | チオピラノース化合物等の製造方法 |
| TWI678373B (zh) | 2014-10-31 | 2019-12-01 | 日商富士軟片股份有限公司 | 硫代核苷衍生物或其鹽及醫藥組合物 |
| WO2016144918A1 (en) | 2015-03-06 | 2016-09-15 | Atea Pharmaceuticals, Inc. | β-D-2'-DEOXY-2'α-FLUORO-2'-β-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT |
| US10711029B2 (en) | 2016-07-14 | 2020-07-14 | Atea Pharmaceuticals, Inc. | Beta-d-2′-deoxy-2′-alpha-fluoro-2′-beta-c-substituted-4′fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection |
| AU2017319260B2 (en) | 2016-08-31 | 2020-01-30 | Fujifilm Corporation | Anti-tumor agent, anti-tumor effect enhancer, and anti-tumor kit |
| SG11201901457TA (en) | 2016-09-07 | 2019-03-28 | Atea Pharmaceuticals Inc | 2'-substituted-n6-substituted purine nucleotides for rna virus treatment |
| IL295609B2 (en) | 2017-02-01 | 2023-11-01 | Atea Pharmaceuticals Inc | Nucleotide hemisulfate salt for the treatment of hepatitis C virus |
| TW201932119A (zh) | 2018-01-29 | 2019-08-16 | 日商富士軟片股份有限公司 | 膽道癌用抗腫瘤劑和膽道癌的處理方法 |
| CN112351799A (zh) | 2018-04-10 | 2021-02-09 | 阿堤亚制药公司 | 具有硬化的hcv感染患者的治疗 |
| US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
| WO2021191830A1 (en) * | 2020-03-25 | 2021-09-30 | Simon Fraser University | Methods and reagents for synthesizing nucleosides and analogues thereof |
| JP2024525164A (ja) | 2021-06-17 | 2024-07-10 | アテア ファーマシューティカルズ， インコーポレイテッド | 有利な抗ｈｃｖ併用療法 |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
| US4625020A (en) | 1983-11-18 | 1986-11-25 | Bristol-Myers Company | Nucleoside process |
| US4666892A (en) | 1984-03-06 | 1987-05-19 | Sloan-Kettering Memorial Cancer Center | Method and composition for hepatitis treatment with pyrimidine nucleoside compounds |
| US4681933A (en) * | 1986-05-01 | 1987-07-21 | University Of Georgia Research Foundation, Inc. | 2',3'-dideoxy-5-substituted uridines and related compounds as antiviral agents |
| US5446029A (en) * | 1986-07-04 | 1995-08-29 | Medivir Ab | Anti-retroviral activity of 2',3'-dideoxy-3'-fluoronucleosides |
| DD279407A1 (de) * | 1986-07-24 | 1990-06-06 | Akad Wissenschaften Ddr | Verfahren zur herstellung eines mittels gegen aids |
| US5215970A (en) * | 1987-04-16 | 1993-06-01 | Medivir Ab | Nucleosides and nucleotide analogues, pharmaceutical composition and processes for the preparation of the compounds |
| DE3715666A1 (de) | 1987-05-11 | 1988-11-24 | Kodak Ag | Kassettenentlade- und beladegeraet |
| GB8712115D0 (en) | 1987-05-22 | 1987-06-24 | Hoffmann La Roche | Pyrimidine derivatives |
| US5246924A (en) | 1987-09-03 | 1993-09-21 | Sloan-Kettering Institute For Cancer Research | Method for treating hepatitis B virus infections using 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-ethyluracil |
| GB8726136D0 (en) * | 1987-11-07 | 1987-12-09 | Wellcome Found | Therapeutic nucleosides |
| US4908440A (en) | 1987-11-12 | 1990-03-13 | Bristol Myers Company | 2',3'-dideoxy-2'-fluoroarabinopyrimidine nucleosides |
| SE8802173D0 (sv) | 1988-06-10 | 1988-06-10 | Astra Ab | Pyrimidine derivatives |
| SE8802687D0 (sv) | 1988-07-20 | 1988-07-20 | Astra Ab | Nucleoside derivatives |
| US5034518A (en) | 1989-05-23 | 1991-07-23 | Southern Research Institute | 2-fluoro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl) adenine nucleosides |
| DD293498A5 (de) | 1989-07-20 | 1991-09-05 | Zi Fuer Molekularbiologie Der Adw,De | Verfahren zur herstellung eines mittels fuer die behandlung oder prophylaxe von hepatits-infektionen bei mensch und tier |
| US5128458A (en) | 1990-04-20 | 1992-07-07 | Southern Research Institute | 2',3'-dideoxy-4'-thioribonucleosides as antiviral agents |
| EP0463470A3 (en) | 1990-06-22 | 1992-08-05 | F. Hoffmann-La Roche Ag | Process for the preparation of a fluorotetrahydrofuranone derivative |
| JPH0477485A (ja) * | 1990-07-19 | 1992-03-11 | Yamasa Shoyu Co Ltd | ２’，３’―ジデヒドロ―２’，３’―ジデオキシウリジン誘導体およびその製造法 |
| US5817799A (en) | 1990-07-23 | 1998-10-06 | The United States Of America As Represented By The Department Of Health And Human Services | 2'-Fluorofuranosyl derivatives and methods for preparing 2'-fluoropyrimidine and 2'-fluoropurine nucleosides |
| IT1246983B (it) | 1990-11-13 | 1994-12-12 | Consiglio Nazionale Ricerche | L-2'-desossiuridine e composizioni farmaceutiche che le contengono. |
| WO1993014103A1 (en) * | 1992-01-06 | 1993-07-22 | The Wellcome Foundation Limited | Therapeutic nucleosides |
| GB9200150D0 (en) * | 1992-01-06 | 1992-02-26 | Wellcome Found | Therapeutic nucleosides |
| 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 |
| WO1994014831A1 (en) | 1992-12-18 | 1994-07-07 | The University Of Alberta | Dihydropyrimidine nucleosides with antiviral properties |
| 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 |
| US5587362A (en) | 1994-01-28 | 1996-12-24 | Univ. Of Ga Research Foundation | L-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 |
| US6355790B1 (en) * | 1997-06-03 | 2002-03-12 | University Of Rochester | Inhibition of HIV replication using a mutated transfer RNA primer |
| EA200700564A1 (ru) | 1998-02-25 | 2007-08-31 | Эмори Юниверсити | 2`-фторнуклеозиды |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| YU92202A (sh) | 2000-05-26 | 2006-01-16 | Idenix (Cayman) Limited | Metode i smeše za lečenje flavi virusa i pesti virusa |
-
2002
- 2002-06-24 BR BR0210594-2A patent/BR0210594A/pt not_active IP Right Cessation
- 2002-06-24 KR KR1020037016775A patent/KR20050059975A/ko not_active Ceased
- 2002-06-24 CA CA002451745A patent/CA2451745A1/en not_active Abandoned
- 2002-06-24 US US10/179,612 patent/US6949522B2/en not_active Expired - Fee Related
- 2002-06-24 WO PCT/US2002/020245 patent/WO2003000200A2/en not_active Ceased
- 2002-06-24 CN CNB028164555A patent/CN100343268C/zh not_active Expired - Fee Related
- 2002-06-24 EP EP02756310A patent/EP1478322A4/en not_active Withdrawn
- 2002-06-24 JP JP2003506646A patent/JP2005503358A/ja active Pending
- 2002-06-24 AU AU2002322325A patent/AU2002322325A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003000200A3 (en) | 2004-09-02 |
| BR0210594A (pt) | 2005-11-01 |
| CN1599744A (zh) | 2005-03-23 |
| US20050119286A1 (en) | 2005-06-02 |
| EP1478322A4 (en) | 2007-08-08 |
| EP1478322A2 (en) | 2004-11-24 |
| JP2005503358A (ja) | 2005-02-03 |
| CN100343268C (zh) | 2007-10-17 |
| HK1076473A1 (en) | 2006-01-20 |
| US6949522B2 (en) | 2005-09-27 |
| WO2003000200A2 (en) | 2003-01-03 |
| CA2451745A1 (en) | 2003-01-03 |
| AU2002322325A1 (en) | 2003-01-08 |
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