MXPA04012802A - Ester 2'-c-metil-3'-o-l-valina de ribofuranosil-citidina para el tratamiento de infecciones por flaviviridae. - Google Patents
Ester 2'-c-metil-3'-o-l-valina de ribofuranosil-citidina para el tratamiento de infecciones por flaviviridae.Info
- Publication number
- MXPA04012802A MXPA04012802A MXPA04012802A MXPA04012802A MXPA04012802A MX PA04012802 A MXPA04012802 A MX PA04012802A MX PA04012802 A MXPA04012802 A MX PA04012802A MX PA04012802 A MXPA04012802 A MX PA04012802A MX PA04012802 A MXPA04012802 A MX PA04012802A
- Authority
- MX
- Mexico
- Prior art keywords
- compound
- interferon
- pharmaceutically acceptable
- mcyd
- virus
- Prior art date
Links
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
- C07K9/001—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence having less than 12 amino acids and not being part of a ring structure
- C07K9/003—Peptides being substituted by heterocyclic radicals, e.g. bleomycin, phleomycin
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- 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
- A61K31/7068—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- 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
- A61K31/7068—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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-
- 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
- C07H19/067—Pyrimidine radicals with ribosyl as the saccharide radical
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| PCT/US2003/020431 WO2004002422A2 (en) | 2002-06-28 | 2003-06-27 | 2’-c-methyl-3’-o-l-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
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Families Citing this family (191)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY164523A (en) * | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| EA007867B1 (ru) * | 2000-05-26 | 2007-02-27 | Айденикс (Кайман) Лимитед | Композиции для лечения флавивирусных и пестивирусных инфекций и способы их применения |
| US6875751B2 (en) * | 2000-06-15 | 2005-04-05 | Idenix Pharmaceuticals, Inc. | 3′-prodrugs of 2′-deoxy-β-L-nucleosides |
| US7608600B2 (en) | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| 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 |
| MXPA04012802A (es) * | 2002-06-28 | 2005-04-19 | Idenix Cayman Ltd | Ester 2'-c-metil-3'-o-l-valina de ribofuranosil-citidina para el tratamiento de infecciones por flaviviridae. |
| WO2004009020A2 (en) | 2002-07-24 | 2004-01-29 | Merck & Co., Inc. | Pyrrolopyrimidine thionucleoside analogs as antivirals |
| NZ538457A (en) * | 2002-09-30 | 2008-04-30 | Genelabs Tech Inc | Nucleoside derivatives for treating hepatitis C virus infection |
| US7094768B2 (en) * | 2002-09-30 | 2006-08-22 | Genelabs Technologies, Inc. | Nucleoside derivatives for treating hepatitis C virus infection |
| KR101026294B1 (ko) | 2002-10-31 | 2011-03-31 | 메타베이시스 테라퓨틱스, 인크. | 1,3-프로판-1-아릴 디올의 신규 시클릭 포스페이트디에스테르 및 프로드럭 제조에서의 이들의 용도 |
| EP1576138B1 (en) * | 2002-11-15 | 2017-02-01 | Idenix Pharmaceuticals LLC. | 2'-methyl nucleosides in combination with interferon and flaviviridae mutation |
| CA2509687C (en) * | 2002-12-12 | 2012-08-14 | Idenix (Cayman) Limited | Process for the production of 2'-branched nucleosides |
| US20040181051A1 (en) * | 2002-12-23 | 2004-09-16 | Richard Storer | Process for the production of 3'-nucleoside prodrugs |
| WO2004084796A2 (en) * | 2003-03-28 | 2004-10-07 | Pharmasset Ltd. | Compounds for the treatment of flaviviridae infections |
| ES2726998T3 (es) | 2003-05-30 | 2019-10-11 | Gilead Pharmasset Llc | Análogos de nucleósidos fluorados modificados |
| ATE478886T1 (de) * | 2003-07-25 | 2010-09-15 | Idenix Pharmaceuticals Inc | Purin nucleoside für die behandlung von durch flavividrae verursachten krankheiten, einschliesslich hepatitis c |
| WO2005018330A1 (en) * | 2003-08-18 | 2005-03-03 | Pharmasset, Inc. | Dosing regimen for flaviviridae therapy |
| GB0320638D0 (en) | 2003-09-03 | 2003-10-01 | Novartis Ag | Organic compounds |
| GB0500020D0 (en) | 2005-01-04 | 2005-02-09 | Novartis Ag | Organic compounds |
| US20050182252A1 (en) | 2004-02-13 | 2005-08-18 | Reddy K. R. | Novel 2'-C-methyl nucleoside derivatives |
| KR20120091276A (ko) | 2004-02-20 | 2012-08-17 | 베링거 인겔하임 인터내셔날 게엠베하 | 바이러스 폴리머라제 억제제 |
| MXPA06011420A (es) * | 2004-04-01 | 2007-04-20 | Cardiome Pharma Corp | Compuestos pegilados de modulacion de canal de iones. |
| JP5055564B2 (ja) | 2004-06-15 | 2012-10-24 | メルク・シャープ・エンド・ドーム・コーポレイション | Ｒｎａ依存性ｒｎａウイルスポリメラーゼの阻害剤としてのｃ−プリンヌクレオシド類似体 |
| WO2006000922A2 (en) * | 2004-06-23 | 2006-01-05 | Idenix (Cayman) Limited | 5-aza-7-deazapurine derivatives for treating infections with flaviviridae |
| CN101023094B (zh) | 2004-07-21 | 2011-05-18 | 法莫赛特股份有限公司 | 烷基取代的2-脱氧-2-氟代-d-呋喃核糖基嘧啶和嘌呤及其衍生物的制备 |
| EP1795206A4 (en) | 2004-08-11 | 2009-07-22 | Chugai Pharmaceutical Co Ltd | MEDICAMENT FOR THE TREATMENT OF HCV OR THE PREVENTION OF HCV INFECTION |
| AU2005285045B2 (en) | 2004-09-14 | 2011-10-13 | Gilead Sciences, Inc. | Preparation of 2'fluoro-2'- alkyl- substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives |
| KR20070073805A (ko) * | 2004-09-24 | 2007-07-10 | 이데닉스 (케이만) 리미티드 | 플라비바이러스, 페스티바이러스 및 헤파시바이러스를치료하기 위한 방법 및 조성물 |
| MX2007007779A (es) * | 2004-12-23 | 2007-08-14 | Novartis Ag | Composiciones para el tratamiento de infeccion de hepatitis c. |
| US7524831B2 (en) | 2005-03-02 | 2009-04-28 | Schering Corporation | Treatments for Flaviviridae virus infection |
| GT200600119A (es) * | 2005-03-24 | 2006-10-25 | Composiciones farmaceuticas | |
| US20090156545A1 (en) * | 2005-04-01 | 2009-06-18 | Hostetler Karl Y | Substituted Phosphate Esters of Nucleoside Phosphonates |
| EP1866319B1 (en) | 2005-04-01 | 2011-11-23 | The Regents of The University of California | Phosphono-pent-2-en-1-yl nucleosides and analogs |
| US7879797B2 (en) | 2005-05-02 | 2011-02-01 | Merck Sharp & Dohme Corp. | HCV NS3 protease inhibitors |
| WO2006138507A1 (en) | 2005-06-17 | 2006-12-28 | Novartis Ag | Use of sanglifehrin in hcv |
| US7470664B2 (en) | 2005-07-20 | 2008-12-30 | Merck & Co., Inc. | HCV NS3 protease inhibitors |
| AU2006275605B2 (en) | 2005-08-01 | 2011-01-06 | Merck Sharp & Dohme Corp. | Macrocyclic peptides as HCV NS3 protease inhibitors |
| WO2007025043A2 (en) * | 2005-08-23 | 2007-03-01 | Idenix Pharmaceuticals, Inc. | Seven-membered ring nucleosides |
| NZ567262A (en) * | 2005-09-30 | 2011-12-22 | Scynexis Inc | Cyclosporin derivatives and their use for the treatment and prevention of hepatitis C infection |
| JP5322647B2 (ja) * | 2005-09-30 | 2013-10-23 | スシネキス インク | ウイルス感染の治療及び予防のためのシクロスポリンａのアリールアルキル及びヘテロアリールアルキル誘導体 |
| WO2007065829A1 (en) | 2005-12-09 | 2007-06-14 | F. Hoffmann-La Roche Ag | Antiviral nucleosides |
| US7781576B2 (en) * | 2005-12-23 | 2010-08-24 | Idenix Pharmaceuticals, Inc. | Process for preparing a synthetic intermediate for preparation of branched nucleosides |
| US8895531B2 (en) | 2006-03-23 | 2014-11-25 | Rfs Pharma Llc | 2′-fluoronucleoside phosphonates as antiviral agents |
| CN101460488A (zh) | 2006-04-04 | 2009-06-17 | 弗·哈夫曼-拉罗切有限公司 | 用于hcv治疗的3’,5’-二-o-酰化核苷 |
| WO2007133865A2 (en) | 2006-04-11 | 2007-11-22 | Novartis Ag | Hcv/hiv inhibitors an their uses |
| GB0609492D0 (en) | 2006-05-15 | 2006-06-21 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| KR20090021163A (ko) * | 2006-05-16 | 2009-02-27 | 도쿄 메트로폴리탄 오거니제이션 포 메디칼 리서치 | Ｈｃｖ 감염증을 치료 또는 예방하기 위한 의약 조성물 |
| US8058260B2 (en) * | 2006-05-22 | 2011-11-15 | Xenoport, Inc. | 2′-C-methyl-ribofuranosyl cytidine prodrugs, pharmaceutical compositions and uses thereof |
| GB0612423D0 (en) | 2006-06-23 | 2006-08-02 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| WO2008024763A2 (en) * | 2006-08-25 | 2008-02-28 | Wyeth | Identification and characterization of hcv replicon variants with reduced susceptibility to hcv-796, and methods related thereto |
| US20080161324A1 (en) * | 2006-09-14 | 2008-07-03 | Johansen Lisa M | Compositions and methods for treatment of viral diseases |
| WO2008045419A1 (en) * | 2006-10-10 | 2008-04-17 | Pharmasset, Inc. | Preparation of nucleosides ribofuranosyl pyrimidines |
| JP2010505902A (ja) | 2006-10-10 | 2010-02-25 | メディヴィル・アクチエボラーグ | Ｈｃｖヌクレオシド阻害剤 |
| EP2079479B1 (en) | 2006-10-24 | 2014-11-26 | Merck Sharp & Dohme Corp. | Hcv ns3 protease inhibitors |
| AU2007309546A1 (en) | 2006-10-24 | 2008-05-02 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | HCV NS3 protease inhibitors |
| CA2667266C (en) | 2006-10-24 | 2015-11-24 | Merck & Co., Inc. | Hcv ns3 protease inhibitors |
| WO2008057208A2 (en) | 2006-10-27 | 2008-05-15 | Merck & Co., Inc. | Hcv ns3 protease inhibitors |
| EP2086982B1 (en) | 2006-10-27 | 2018-08-29 | Merck Sharp & Dohme Corp. | Hcv ns3 protease inhibitors |
| AU2007316681B2 (en) | 2006-11-09 | 2013-01-24 | F. Hoffmann-La Roche Ag | Thiazole and oxazole-substituted arylamides |
| US8501933B2 (en) | 2006-11-09 | 2013-08-06 | Roche Palo Alto Llc | Thiazole and oxazole-substituted arylamides as P2X3 and P2X2/3 antagonists |
| WO2008069917A2 (en) | 2006-11-20 | 2008-06-12 | Scynexis, Inc. | Novel cyclic peptides |
| GB0625349D0 (en) | 2006-12-20 | 2007-01-31 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| CN103224506A (zh) | 2006-12-20 | 2013-07-31 | P.安杰莱蒂分子生物学研究所 | 抗病毒的吲哚 |
| GB0625345D0 (en) | 2006-12-20 | 2007-01-31 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| US20080261913A1 (en) | 2006-12-28 | 2008-10-23 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of liver disorders |
| US8071568B2 (en) | 2007-01-05 | 2011-12-06 | Merck Sharp & Dohme Corp. | Nucleoside aryl phosphoramidates for the treatment of RNA-dependent RNA viral infection |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| GB0709791D0 (en) * | 2007-05-22 | 2007-06-27 | Angeletti P Ist Richerche Bio | Antiviral agents |
| EP2178885A1 (en) | 2007-07-17 | 2010-04-28 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Macrocyclic indole derivatives for the treatment of hepatitis c infections |
| AU2008277377B2 (en) | 2007-07-19 | 2013-08-01 | Msd Italia S.R.L. | Macrocyclic compounds as antiviral agents |
| US8227431B2 (en) * | 2008-03-17 | 2012-07-24 | Hetero Drugs Limited | Nucleoside derivatives |
| TW200946541A (en) | 2008-03-27 | 2009-11-16 | Idenix Pharmaceuticals Inc | Solid forms of an anti-HIV phosphoindole compound |
| WO2009134624A1 (en) | 2008-04-28 | 2009-11-05 | Merck & Co., Inc. | Hcv ns3 protease inhibitors |
| US20090306033A1 (en) * | 2008-06-06 | 2009-12-10 | Keqiang Li | Novel cyclic peptides |
| US9090671B2 (en) * | 2008-06-06 | 2015-07-28 | Scynexis, Inc. | Macrocyclic peptides |
| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| US20100003217A1 (en) | 2008-07-02 | 2010-01-07 | Erika Cretton-Scott | Compounds and Pharmaceutical Compositions for the Treatment of Viral Infections |
| SI2310095T1 (sl) | 2008-07-22 | 2013-01-31 | Merck Sharp & Dohme Corp. | Makrocikliäśne kuinoksalinske spojine kot hcv ns3 proteazni inhibitorji |
| US20110171192A1 (en) | 2008-09-05 | 2011-07-14 | Hiroshi Tomiyama | Substituted amine derivative and medicinal composition comprising same as the active ingredient |
| EP2368989A4 (en) | 2008-11-26 | 2012-09-26 | Chugai Pharmaceutical Co Ltd | OLOGORIBONUCLEOTIDE OR PEPTIDE NUCLEIC ACID CAPABLE OF INHIBITING HEPATITIS C VIRUS ACTIVITY |
| KR20110099138A (ko) | 2008-12-23 | 2011-09-06 | 파마셋 인코포레이티드 | 뉴클레오시드 포스포르아미데이트 |
| KR20110098849A (ko) | 2008-12-23 | 2011-09-01 | 파마셋 인코포레이티드 | 뉴클레오시드 유사체 |
| SG172363A1 (en) | 2008-12-23 | 2011-07-28 | Pharmasset Inc | Synthesis of purine nucleosides |
| WO2010076329A1 (en) | 2008-12-31 | 2010-07-08 | Scynexis, Inc. | Derivatives of cyclosporin a |
| WO2010082050A1 (en) | 2009-01-16 | 2010-07-22 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Macrocyclic and 7-aminoalkyl-substituted benzoxazocines for treatment of hepatitis c infections |
| GB0900914D0 (en) | 2009-01-20 | 2009-03-04 | Angeletti P Ist Richerche Bio | Antiviral agents |
| EP2403860B1 (en) | 2009-03-04 | 2015-11-04 | IDENIX Pharmaceuticals, Inc. | Phosphothiophene and phosphothiazole as hcv polymerase inhibitors |
| US20110182850A1 (en) | 2009-04-10 | 2011-07-28 | Trixi Brandl | Organic compounds and their uses |
| US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
| US20100310656A1 (en) * | 2009-04-27 | 2010-12-09 | Immunitor USA, Inc. | Immunotherapy and prevention of autoimmune hepatitis |
| TWI583692B (zh) | 2009-05-20 | 2017-05-21 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
| WO2010135520A1 (en) * | 2009-05-20 | 2010-11-25 | Chimerix, Inc. | Compounds, compositions and methods for treating viral infection |
| US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| SG177308A1 (en) * | 2009-06-22 | 2012-02-28 | Hoffmann La Roche | Novel biphenyl and phenyl-pyridine amides |
| ES2593405T3 (es) * | 2009-06-22 | 2016-12-09 | F. Hoffmann-La Roche Ag | Nuevas arilamidas sustituidas por benzoxazolona |
| WO2010149634A1 (en) * | 2009-06-22 | 2010-12-29 | F. Hoffmann-La Roche Ag | Novel indole, indazole and benzimidazole arylamides as p2x3 and/or p2x2/3 antagonists |
| US20110020272A1 (en) * | 2009-07-24 | 2011-01-27 | Ulrich Schubert | Combination therapy for treating hepatitis viral infection |
| WO2011014487A1 (en) | 2009-07-30 | 2011-02-03 | Merck Sharp & Dohme Corp. | Hepatitis c virus ns3 protease inhibitors |
| US9284307B2 (en) | 2009-08-05 | 2016-03-15 | Idenix Pharmaceuticals Llc | Macrocyclic serine protease inhibitors |
| WO2011058084A1 (en) | 2009-11-14 | 2011-05-19 | F. Hoffmann-La Roche Ag | Biomarkers for predicting rapid response to hcv treatment |
| EA201270632A1 (ru) * | 2009-11-16 | 2013-01-30 | Юниверсити Оф Джорджия Рисерч Фаундейшн, Инк. | 2'-фтор-6'-метилен карбоциклические нуклеозиды и способы лечения вирусных инфекций |
| WO2011063076A1 (en) | 2009-11-19 | 2011-05-26 | Itherx Pharmaceuticals, Inc. | Methods of treating hepatitis c virus with oxoacetamide compounds |
| MX2012005703A (es) | 2009-12-02 | 2012-06-12 | Hoffmann La Roche | Biomarcadores para pronosticar una respuesta prolongada al tratamiento contra el vhc. |
| RU2554087C2 (ru) | 2009-12-18 | 2015-06-27 | Айденикс Фармасьютикалз, Инк. | 5,5-конденсированные ариленовые или гетероариленовые ингибиторы вируса гепатита с |
| US8563530B2 (en) | 2010-03-31 | 2013-10-22 | Gilead Pharmassel LLC | Purine nucleoside phosphoramidate |
| PL2552930T3 (pl) | 2010-03-31 | 2016-02-29 | Gilead Pharmasset Llc | Krystaliczny 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-diokso-3,4-dihydropirymidyn-1-(2H)-ylo)-4-fluoro-3-hydroksy-4-metylotetrahydrofuran-2-ylo)metoksy)(fenoksy)fosforylo)amino)propanian (S)-izopropylu |
| CA2795054A1 (en) | 2010-04-01 | 2011-10-06 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of viral infections |
| KR20130110170A (ko) | 2010-09-22 | 2013-10-08 | 앨리오스 바이오파마 인크. | 치환된 뉴클레오타이드 유사체 |
| WO2012040124A1 (en) | 2010-09-22 | 2012-03-29 | Alios Biopharma, Inc. | Azido nucleosides and nucleotide analogs |
| CA2811799A1 (en) | 2010-10-08 | 2012-04-12 | Novartis Ag | Vitamin e formulations of sulfamide ns3 inhibitors |
| AR084044A1 (es) | 2010-11-30 | 2013-04-17 | Pharmasset Inc | Compuestos 2’-espiro-nucleosidos |
| WO2012080050A1 (en) | 2010-12-14 | 2012-06-21 | F. Hoffmann-La Roche Ag | Solid forms of a phenoxybenzenesulfonyl compound |
| AR085352A1 (es) | 2011-02-10 | 2013-09-25 | Idenix Pharmaceuticals Inc | Inhibidores macrociclicos de serina proteasa, sus composiciones farmaceuticas y su uso para tratar infecciones por hcv |
| US20120252721A1 (en) | 2011-03-31 | 2012-10-04 | Idenix Pharmaceuticals, Inc. | Methods for treating drug-resistant hepatitis c virus infection with a 5,5-fused arylene or heteroarylene hepatitis c virus inhibitor |
| CA2843324A1 (en) | 2011-03-31 | 2012-11-15 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of viral infections |
| CN102775458B (zh) * | 2011-05-09 | 2015-11-25 | 中国人民解放军军事医学科学院毒物药物研究所 | β-D-(2’R)-2’-脱氧—2’-氟-2’-C-甲基胞苷衍生物的制备及用途 |
| TW201329096A (zh) | 2011-09-12 | 2013-07-16 | Idenix Pharmaceuticals Inc | 經取代羰氧基甲基磷酸醯胺化合物及用於治療病毒感染之藥學組成物 |
| CA2847892A1 (en) | 2011-09-12 | 2013-03-21 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of viral infections |
| ME03009B (me) | 2011-09-16 | 2018-10-20 | Gilead Pharmasset Llc | Metode za lecenje hcv-a |
| WO2013056046A1 (en) | 2011-10-14 | 2013-04-18 | Idenix Pharmaceuticals, Inc. | Substituted 3',5'-cyclic phosphates of purine nucleotide compounds and pharmaceutical compositions for the treatment of viral infections |
| US9328138B2 (en) | 2011-11-15 | 2016-05-03 | Msd Italia S.R.L. | HCV NS3 protease inhibitors |
| US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
| AU2012345732B2 (en) | 2011-11-30 | 2016-07-14 | Emory University | Antiviral JAK inhibitors useful in treating or preventing retroviral and other viral infections |
| AU2012358804B2 (en) | 2011-12-22 | 2018-04-19 | Alios Biopharma, Inc. | Substituted phosphorothioate nucleotide analogs |
| AP2014007796A0 (en) | 2011-12-22 | 2014-07-31 | Alios Biopharma Inc | Substituted nucleosides, nucleotides and analogs thereof |
| WO2013133927A1 (en) | 2012-02-13 | 2013-09-12 | Idenix Pharmaceuticals, Inc. | Pharmaceutical compositions of 2'-c-methyl-guanosine, 5'-[2-[(3-hydroxy-2,2-dimethyl-1-oxopropyl)thio]ethyl n-(phenylmethyl)phosphoramidate] |
| AU2013221571A1 (en) | 2012-02-14 | 2014-08-28 | University Of Georgia Research Foundation, Inc. | Spiro [2.4] heptanes for treatment of Flaviviridae infections |
| USRE48171E1 (en) | 2012-03-21 | 2020-08-25 | Janssen Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| US8916538B2 (en) | 2012-03-21 | 2014-12-23 | Vertex Pharmaceuticals Incorporated | Solid forms of a thiophosphoramidate nucleotide prodrug |
| US9441007B2 (en) | 2012-03-21 | 2016-09-13 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| WO2013142157A1 (en) | 2012-03-22 | 2013-09-26 | Alios Biopharma, Inc. | Pharmaceutical combinations comprising a thionucleotide analog |
| JP6165848B2 (ja) | 2012-05-22 | 2017-07-19 | イデニク ファーマシューティカルズ エルエルシー | 肝疾患のためのｄ−アミノ酸化合物 |
| US9296778B2 (en) | 2012-05-22 | 2016-03-29 | Idenix Pharmaceuticals, Inc. | 3′,5′-cyclic phosphate prodrugs for HCV infection |
| WO2013177188A1 (en) | 2012-05-22 | 2013-11-28 | Idenix Pharmaceuticals, Inc. | 3',5'-cyclic phosphoramidate prodrugs for hcv infection |
| PL2861611T3 (pl) | 2012-05-25 | 2017-08-31 | Janssen Sciences Ireland Uc | Nukleozydy uracylowe spirooksetanu |
| EP2900682A1 (en) | 2012-09-27 | 2015-08-05 | IDENIX Pharmaceuticals, Inc. | Esters and malonates of sate prodrugs |
| SG11201502750UA (en) | 2012-10-08 | 2015-06-29 | Idenix Pharmaceuticals Inc | 2'-chloro nucleoside analogs for hcv infection |
| US20140112886A1 (en) | 2012-10-19 | 2014-04-24 | Idenix Pharmaceuticals, Inc. | Dinucleotide compounds for hcv infection |
| US10723754B2 (en) | 2012-10-22 | 2020-07-28 | Idenix Pharmaceuticals Llc | 2′,4′-bridged nucleosides for HCV infection |
| WO2014074725A1 (en) * | 2012-11-07 | 2014-05-15 | Ohio State Innovation Foundation | Substituted gemcitabine aryl amide analogs |
| EP2938624A1 (en) | 2012-11-14 | 2015-11-04 | IDENIX Pharmaceuticals, Inc. | D-alanine ester of sp-nucleoside analog |
| EP2920195A1 (en) | 2012-11-14 | 2015-09-23 | IDENIX Pharmaceuticals, Inc. | D-alanine ester of rp-nucleoside analog |
| EP2935304A1 (en) | 2012-12-19 | 2015-10-28 | IDENIX Pharmaceuticals, Inc. | 4'-fluoro nucleosides for the treatment of hcv |
| UA118256C2 (uk) | 2013-01-31 | 2018-12-26 | Гіліад Фармассет Елелсі | Комбінований склад двох противірусних сполук |
| US10034893B2 (en) * | 2013-02-01 | 2018-07-31 | Enanta Pharmaceuticals, Inc. | 5, 6-D2 uridine nucleoside/tide derivatives |
| WO2014121418A1 (en) | 2013-02-07 | 2014-08-14 | Merck Sharp & Dohme Corp. | Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c |
| WO2014121417A1 (en) | 2013-02-07 | 2014-08-14 | Merck Sharp & Dohme Corp. | Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c |
| WO2014137926A1 (en) | 2013-03-04 | 2014-09-12 | Idenix Pharmaceuticals, Inc. | 3'-deoxy nucleosides for the treatment of hcv |
| WO2014137930A1 (en) | 2013-03-04 | 2014-09-12 | Idenix Pharmaceuticals, Inc. | Thiophosphate nucleosides for the treatment of hcv |
| EP2970357B1 (en) | 2013-03-13 | 2025-01-01 | Idenix Pharmaceuticals LLC | Amino acid phosphoramidate pronucleotides of 2'-cyano, azido and amino nucleosides for the treatment of hcv |
| EP2981542B1 (en) | 2013-04-01 | 2021-09-15 | Idenix Pharmaceuticals LLC | 2',4'-fluoro nucleosides for the treatment of hcv |
| CA2909273A1 (en) | 2013-04-12 | 2014-10-16 | Achillion Pharmaceuticals, Inc. | Deuterated nucleoside prodrugs useful for treating hcv |
| WO2014197578A1 (en) | 2013-06-05 | 2014-12-11 | Idenix Pharmaceuticals, Inc. | 1',4'-thio nucleosides for the treatment of hcv |
| EP3027636B1 (en) | 2013-08-01 | 2022-01-05 | Idenix Pharmaceuticals LLC | D-amino acid phosphoramidate pronucleotides of halogeno pyrimidine compounds for liver disease |
| US20150064253A1 (en) | 2013-08-27 | 2015-03-05 | Gilead Pharmasset Llc | Combination formulation of two antiviral compounds |
| EP3046924A1 (en) | 2013-09-20 | 2016-07-27 | IDENIX Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| WO2015061683A1 (en) | 2013-10-25 | 2015-04-30 | Idenix Pharmaceuticals, Inc. | D-amino acid phosphoramidate and d-alanine thiophosphoramidate pronucleotides of nucleoside compounds useful for the treatment of hcv |
| EP3063165A1 (en) | 2013-11-01 | 2016-09-07 | Idenix Pharmaceuticals LLC | D-alanine phosphoramidate pronucleotides of 2'-methyl 2'-fluoro guanosine nucleoside compounds for the treatment of hcv |
| WO2015081297A1 (en) | 2013-11-27 | 2015-06-04 | Idenix Pharmaceuticals, Inc. | 2'-dichloro and 2'-fluoro-2'-chloro nucleoside analogues for hcv infection |
| EP3083654A1 (en) | 2013-12-18 | 2016-10-26 | Idenix Pharmaceuticals LLC | 4'-or nucleosides for the treatment of hcv |
| US10449210B2 (en) | 2014-02-13 | 2019-10-22 | Ligand Pharmaceuticals Inc. | Prodrug compounds and their uses |
| US20170135990A1 (en) | 2014-03-05 | 2017-05-18 | Idenix Pharmaceuticals Llc | Pharmaceutical compositions comprising a 5,5-fused heteroarylene flaviviridae inhibitor and their use for treating or preventing flaviviridae infection |
| WO2015134780A1 (en) | 2014-03-05 | 2015-09-11 | Idenix Pharmaceuticals, Inc. | Solid prodrug forms of 2'-chloro-2'-methyl uridine for hcv |
| US20170066779A1 (en) | 2014-03-05 | 2017-03-09 | Idenix Pharmaceuticals Llc | Solid forms of a flaviviridae virus inhibitor compound and salts thereof |
| US10202411B2 (en) | 2014-04-16 | 2019-02-12 | Idenix Pharmaceuticals Llc | 3′-substituted methyl or alkynyl nucleosides nucleotides for the treatment of HCV |
| EP3154996B1 (en) * | 2014-06-10 | 2020-03-11 | Agilent Technologies, Inc. | Protecting groups for "z nucleotide" and methods thereof |
| EP3164136A4 (en) | 2014-07-02 | 2018-04-04 | Ligand Pharmaceuticals, Inc. | Prodrug compounds and uses therof |
| WO2016033164A1 (en) | 2014-08-26 | 2016-03-03 | Enanta Pharmaceuticals, Inc. | Nucleoside and nucleotide derivatives |
| WO2016073756A1 (en) | 2014-11-06 | 2016-05-12 | Enanta Pharmaceuticals, Inc. | Deuterated nucleoside/tide derivatives |
| US9732110B2 (en) | 2014-12-05 | 2017-08-15 | Enanta Pharmaceuticals, Inc. | Nucleoside and nucleotide derivatives |
| GEP20247600B (en) | 2015-03-06 | 2024-02-26 | Atea Pharmaceuticals Inc | B-D-2'-DEOXY-2'a-FLUORO-2'-B-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT |
| CN106146588A (zh) * | 2015-03-26 | 2016-11-23 | 常州制药厂有限公司 | 一种索非布韦的制备方法 |
| JP6743135B2 (ja) * | 2015-09-02 | 2020-08-19 | アッヴィ・インコーポレイテッド | 抗ウィルス性テトラヒドロフラン誘導体 |
| WO2017197046A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | C3-carbon linked glutarimide degronimers for target protein degradation |
| CN109790143A (zh) | 2016-05-10 | 2019-05-21 | C4医药公司 | 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体 |
| EP3454862B1 (en) | 2016-05-10 | 2024-09-11 | C4 Therapeutics, Inc. | Spirocyclic degronimers for target protein degradation |
| CN109562107A (zh) | 2016-05-10 | 2019-04-02 | C4医药公司 | 用于靶蛋白降解的杂环降解决定子体 |
| 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 |
| EP3865136A1 (en) | 2016-09-07 | 2021-08-18 | ATEA Pharmaceuticals, Inc. | 2'-substituted-n6-substituted purine nucleotides for corona virus treatment |
| CN106432388B (zh) * | 2016-09-14 | 2018-11-30 | 江苏福瑞生物医药有限公司 | (2’r) -2’-脱氧-2’-氟- 2’-甲基脲苷的制备方法 |
| PL3577124T3 (pl) | 2017-02-01 | 2025-04-22 | Atea Pharmaceuticals, Inc. | Sól hemisiarczanowa nukleotydu do leczenia wirusowego zapalenia wątroby typu c |
| EP3641762A4 (en) | 2017-06-20 | 2021-03-10 | C4 Therapeutics, Inc. | N / O-LINKED DEGRONES AND DEGRONIMERS FOR PROTEIN DEGRADATION |
| US10435429B2 (en) | 2017-10-03 | 2019-10-08 | Nucorion Pharmaceuticals, Inc. | 5-fluorouridine monophosphate cyclic triester compounds |
| 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 |
| CN111836818B (zh) | 2018-01-10 | 2023-10-31 | 纽科利制药公司 | 氨基磷(膦)酸缩醛和磷(膦)酸缩醛化合物 |
| US11427550B2 (en) | 2018-01-19 | 2022-08-30 | Nucorion Pharmaceuticals, Inc. | 5-fluorouracil compounds |
| TW202012001A (zh) | 2018-04-10 | 2020-04-01 | 美商亞堤製藥公司 | C型肝炎病毒(hcv)感染硬化之患者的治療 |
| AU2020315394A1 (en) | 2019-07-17 | 2022-02-17 | Nucorion Pharmaceuticals, Inc. | Cyclic deoxyribonucleotide compounds |
| US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
| CN115605492B (zh) | 2020-04-21 | 2025-09-16 | 配体制药股份有限公司 | 核苷酸前药化合物 |
| IL308921A (en) | 2021-06-17 | 2024-01-01 | Atea Pharmaceuticals Inc | Combination anti-HCV therapy is beneficial |
Family Cites Families (236)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6458772B1 (en) | 1909-10-07 | 2002-10-01 | Medivir Ab | Prodrugs |
| US3074929A (en) | 1955-08-11 | 1963-01-22 | Burroughs Wellcome Co | Glycosides of 6-mercaptopurine |
| GB924246A (en) | 1958-12-23 | 1963-04-24 | Wellcome Found | Purine derivatives and their preparation |
| US3116282A (en) | 1960-04-27 | 1963-12-31 | Upjohn Co | Pyrimidine nucleosides and process |
| GB984877A (en) | 1962-08-16 | 1965-03-03 | Waldhof Zellstoff Fab | Improvements in and relating to 6-halonucleosides |
| CH490395A (de) | 1965-11-15 | 1970-05-15 | Merck & Co Inc | Verfahren zur Herstellung neuartiger Nukleoside |
| FR1498856A (enExample) | 1965-11-15 | 1968-01-10 | ||
| FR1521076A (fr) | 1966-05-02 | 1968-04-12 | Merck & Co Inc | Nucléosides de purines substituées |
| DE1695411A1 (de) | 1966-05-02 | 1971-04-15 | Merck & Co Inc | Substituierte Purin-Nucleoside und Verfahren zu deren Herstellung |
| US3480613A (en) | 1967-07-03 | 1969-11-25 | Merck & Co Inc | 2-c or 3-c-alkylribofuranosyl - 1-substituted compounds and the nucleosides thereof |
| DE2122991C2 (de) | 1971-05-04 | 1982-06-09 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur Herstellung von Cytosin- und 6-Azacytosinnucleosiden |
| US3798209A (en) * | 1971-06-01 | 1974-03-19 | Icn Pharmaceuticals | 1,2,4-triazole nucleosides |
| USRE29835E (en) | 1971-06-01 | 1978-11-14 | Icn Pharmaceuticals | 1,2,4-Triazole nucleosides |
| US4022889A (en) | 1974-05-20 | 1977-05-10 | The Upjohn Company | Therapeutic compositions of antibiotic U-44,590 and methods for using the same |
| DE2508312A1 (de) | 1975-02-24 | 1976-09-02 | Schering Ag | Neues verfahren zur herstellung von nucleosiden |
| US4058602A (en) | 1976-08-09 | 1977-11-15 | The United States Of America As Represented By The Department Of Health, Education And Welfare | Synthesis, structure, and antitumor activity of 5,6-dihydro-5-azacytidine |
| DE2757365A1 (de) | 1977-12-20 | 1979-06-21 | Schering Ag | Neues verfahren zur herstellung von nucleosiden |
| DD140254A1 (de) | 1978-12-04 | 1980-02-20 | Dieter Baerwolff | Verfahren zur herstellung von 4-substituierten pyrimidin-nucleosiden |
| DE2852721A1 (de) | 1978-12-06 | 1980-06-26 | Basf Ag | Verfahren zur reindarstellung von kaliumribonat und ribonolacton |
| US4239753A (en) | 1978-12-12 | 1980-12-16 | The Upjohn Company | Composition of matter and process |
| US4522811A (en) * | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US4540707A (en) * | 1983-01-28 | 1985-09-10 | Bayer Aktiengesellschaft | Nafazatrom as a lipoxygenase inhibitor |
| FR2562543B1 (fr) | 1984-04-10 | 1987-09-25 | Elf Aquitaine | Nouveaux phosphonites cycliques, leur preparation et applications |
| NL8403224A (nl) | 1984-10-24 | 1986-05-16 | Oce Andeno Bv | Dioxafosforinanen, de bereiding ervan en de toepassing voor het splitsen van optisch actieve verbindingen. |
| JPS61204193A (ja) | 1985-03-05 | 1986-09-10 | Takeda Chem Ind Ltd | シトシンヌクレオシド類の製造法 |
| US6448392B1 (en) | 1985-03-06 | 2002-09-10 | Chimerix, Inc. | Lipid derivatives of antiviral nucleosides: liposomal incorporation and method of use |
| US5223263A (en) | 1988-07-07 | 1993-06-29 | Vical, Inc. | Liponucleotide-containing liposomes |
| JPS61212592A (ja) | 1985-03-19 | 1986-09-20 | Tokyo Tanabe Co Ltd | Ｄ−リボ−スの製造方法 |
| US4605659A (en) * | 1985-04-30 | 1986-08-12 | Syntex (U.S.A.) Inc. | Purinyl or pyrimidinyl substituted hydroxycyclopentane compounds useful as antivirals |
| JPS61263995A (ja) | 1985-05-16 | 1986-11-21 | Takeda Chem Ind Ltd | シトシンヌクレオシド類の製造法 |
| US4754026A (en) | 1985-06-04 | 1988-06-28 | Takeda Chemical Industries, Ltd. | Conversion of uracil derivatives to cytosine derivatives |
| JPH0699467B2 (ja) | 1987-03-04 | 1994-12-07 | ヤマサ醤油株式会社 | ２▲’▼−デオキシ−２▲’▼（ｓ）−アルキルピリミジンヌクレオシド誘導体 |
| DE3714473A1 (de) | 1987-04-30 | 1988-11-10 | Basf Ag | Kontinuierliches verfahren zur epimerisierung von zuckern, insbesondere von d-arabinose zu d-ribose |
| GB8719367D0 (en) | 1987-08-15 | 1987-09-23 | Wellcome Found | Therapeutic compounds |
| 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 |
| WO1989002733A1 (en) | 1987-09-22 | 1989-04-06 | The Regents Of The University Of California | Liposomal nucleoside analogues for treating aids |
| US4880784A (en) | 1987-12-21 | 1989-11-14 | Brigham Young University | Antiviral methods utilizing ribofuranosylthiazolo[4,5-d]pyrimdine derivatives |
| US4852740A (en) * | 1988-03-11 | 1989-08-01 | Information Packaging Corp. | Holder for flat objects such as computer disks |
| US5122517A (en) | 1988-06-10 | 1992-06-16 | Regents Of The University Of Minnesota | Antiviral combination comprising nucleoside analogs |
| GB8815265D0 (en) | 1988-06-27 | 1988-08-03 | Wellcome Found | Therapeutic nucleosides |
| US6252060B1 (en) * | 1988-07-07 | 2001-06-26 | Nexstar Pharmaceuticals, Inc. | Antiviral liponucleosides: treatment of hepatitis B |
| US6599887B2 (en) * | 1988-07-07 | 2003-07-29 | Chimerix, Inc. | Methods of treating viral infections using antiviral liponucleotides |
| SE8802687D0 (sv) | 1988-07-20 | 1988-07-20 | Astra Ab | Nucleoside derivatives |
| US5744600A (en) | 1988-11-14 | 1998-04-28 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Phosphonomethoxy carbocyclic nucleosides and nucleotides |
| US5616702A (en) | 1988-11-15 | 1997-04-01 | Merrell Pharmaceuticals Inc. | 2-'-ethenylidene cytidine, uridine and guanosine derivatives |
| US5705363A (en) * | 1989-03-02 | 1998-01-06 | The Women's Research Institute | Recombinant production of human interferon τ polypeptides and nucleic acids |
| US5411947A (en) * | 1989-06-28 | 1995-05-02 | Vestar, Inc. | Method of converting a drug to an orally available form by covalently bonding a lipid to the drug |
| US5194654A (en) * | 1989-11-22 | 1993-03-16 | Vical, Inc. | Lipid derivatives of phosphonoacids for liposomal incorporation and method of use |
| US5463092A (en) | 1989-11-22 | 1995-10-31 | Vestar, Inc. | Lipid derivatives of phosphonacids for liposomal incorporation and method of use |
| US6060592A (en) | 1990-01-11 | 2000-05-09 | Isis Pharmaceuticals, Inc. | Pyrimidine nucleoside compounds and oligonucleoside compounds containing same |
| US5200514A (en) * | 1990-01-19 | 1993-04-06 | University Of Georgia Research Foundation, Inc. | Synthesis of 2'-deoxypyrimidine nucleosides |
| US5204466A (en) | 1990-02-01 | 1993-04-20 | Emory University | Method and compositions for the synthesis of bch-189 and related compounds |
| AU7872491A (en) | 1990-05-07 | 1991-11-27 | Vical, Inc. | Lipid prodrugs of salicylate and nonsteroidal anti-inflammatory drugs |
| FR2662165B1 (fr) | 1990-05-18 | 1992-09-11 | Univ Paris Curie | Derives nucleosidiques branches, leur procede de preparation et leur utilisation a titre de medicament. |
| EP0531452A4 (en) | 1990-05-29 | 1993-06-09 | Vical, Inc. | Synthesis of glycerol di- and triphosphate derivatives |
| CA2083961A1 (en) | 1990-05-29 | 1991-11-30 | Henk Van Den Bosch | Synthesis of glycerol di- and triphosphate derivatives |
| US5627165A (en) | 1990-06-13 | 1997-05-06 | Drug Innovation & Design, Inc. | Phosphorous prodrugs and therapeutic delivery systems using same |
| AU651835B2 (en) | 1990-06-13 | 1994-08-04 | Arnold Glazier | Phosphorous prodrugs |
| US5372808A (en) | 1990-10-17 | 1994-12-13 | Amgen Inc. | Methods and compositions for the treatment of diseases with consensus interferon while reducing side effect |
| US5827819A (en) * | 1990-11-01 | 1998-10-27 | Oregon Health Sciences University | Covalent polar lipid conjugates with neurologically active compounds for targeting |
| US5256641A (en) | 1990-11-01 | 1993-10-26 | State Of Oregon | Covalent polar lipid-peptide conjugates for immunological targeting |
| US5543390A (en) * | 1990-11-01 | 1996-08-06 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University | Covalent microparticle-drug conjugates for biological targeting |
| US5543389A (en) | 1990-11-01 | 1996-08-06 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education On Behalf Of The Oregon Health Sciences University, A Non Profit Organization | Covalent polar lipid-peptide conjugates for use in salves |
| US5149794A (en) | 1990-11-01 | 1992-09-22 | State Of Oregon | Covalent lipid-drug conjugates for drug targeting |
| 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 (- |
| JPH04266880A (ja) | 1991-02-22 | 1992-09-22 | Japan Tobacco Inc | ３ −ｄｐａ− ラクトンの製造方法 |
| US5157027A (en) | 1991-05-13 | 1992-10-20 | E. R. Squibb & Sons, Inc. | Bisphosphonate squalene synthetase inhibitors and method |
| WO1993000910A1 (en) | 1991-07-12 | 1993-01-21 | Vical, Inc. | Antiviral liponucleosides: treatment of hepatitis b |
| JPH0525152A (ja) * | 1991-07-22 | 1993-02-02 | Japan Tobacco Inc | ３−ｄｐａ−ラクトンの製造法 |
| US5554728A (en) | 1991-07-23 | 1996-09-10 | Nexstar Pharmaceuticals, Inc. | Lipid conjugates of therapeutic peptides and protease inhibitors |
| TW224053B (enExample) | 1991-09-13 | 1994-05-21 | Paul B Chretien | |
| US5676942A (en) | 1992-02-10 | 1997-10-14 | Interferon Sciences, Inc. | Composition containing human alpha interferon species proteins and method for use thereof |
| 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 |
| US5256797A (en) | 1992-06-22 | 1993-10-26 | Eli Lilly And Company | Process for separating 2-deoxy-2,2-difluoro-D-ribofuranosyl alkylsulfonate anomers |
| 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 |
| 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 |
| 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 |
| AU4508493A (en) | 1992-07-02 | 1994-01-31 | Wellcome Foundation Limited, The | Therapeutic nucleosides |
| DE4224737A1 (de) | 1992-07-27 | 1994-02-03 | Herbert Prof Dr Schott | Neue Cytosinnucleosidanaloga, Verfahren zu ihrer Herstellung und ihre Verwendung |
| IL106840A (en) | 1992-09-01 | 1998-09-24 | Lilly Co Eli | Process for basic anatomization of pentopornosyl nucleosides |
| JPH06135988A (ja) | 1992-10-22 | 1994-05-17 | Toagosei Chem Ind Co Ltd | ヌクレオシド誘導体 |
| GB9226729D0 (en) | 1992-12-22 | 1993-02-17 | Wellcome Found | Therapeutic combination |
| JPH06211890A (ja) | 1993-01-12 | 1994-08-02 | Yamasa Shoyu Co Ltd | ２’−デオキシ−２’（ｓ）−置換アルキルシチジン誘導体 |
| JPH06228186A (ja) | 1993-01-29 | 1994-08-16 | Yamasa Shoyu Co Ltd | ２’−デオキシ−（２’ｓ）−アルキルピリミジンヌクレオシド誘導体 |
| GB9307043D0 (en) | 1993-04-05 | 1993-05-26 | Norsk Hydro As | Chemical compounds |
| JP3693357B2 (ja) | 1993-04-09 | 2005-09-07 | 峯郎 実吉 | 逆転写酵素阻害剤 |
| CA2162574A1 (en) | 1993-05-12 | 1994-11-24 | Karl Y. Hostetler | Acyclovir derivatives for topical use |
| US6156501A (en) | 1993-10-26 | 2000-12-05 | Affymetrix, Inc. | Arrays of modified nucleic acid probes and methods of use |
| US5587362A (en) | 1994-01-28 | 1996-12-24 | Univ. Of Ga Research Foundation | L-nucleosides |
| US5696277A (en) | 1994-11-15 | 1997-12-09 | Karl Y. Hostetler | Antiviral prodrugs |
| HU217772B (hu) | 1994-12-13 | 2000-04-28 | Taiho Pharmaceutical Co. Ltd. | 3'-Helyettesített nukleozidszármazékok, eljárás ezek előállítására és ezeket tartalmazó gyógyszerkészítmények |
| DE19513330A1 (de) * | 1995-04-03 | 1996-10-10 | Schering Ag | Neues Verfahren zur Herstellung von Nucleosiden |
| US5977061A (en) | 1995-04-21 | 1999-11-02 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | N6 - substituted nucleotide analagues and their use |
| JPH0959292A (ja) | 1995-08-25 | 1997-03-04 | Yamasa Shoyu Co Ltd | ４−アミノピリミジンヌクレオシドの製造法 |
| AU709345B2 (en) * | 1995-09-07 | 1999-08-26 | Emory University | Therapeutic azide compounds |
| US5908621A (en) | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
| US5980884A (en) | 1996-02-05 | 1999-11-09 | Amgen, Inc. | Methods for retreatment of patients afflicted with Hepatitis C using consensus interferon |
| GB9609932D0 (en) | 1996-05-13 | 1996-07-17 | Hoffmann La Roche | Use of IL-12 and IFN alpha for the treatment of infectious diseases |
| JP2002503212A (ja) | 1996-10-16 | 2002-01-29 | アイ・シー・エヌ・フアーマシユーテイカルズ・インコーポレイテツド | 単環式ヌクレオシド、その類似体および使用 |
| CZ126799A3 (cs) | 1996-10-16 | 1999-07-14 | Icn Pharmaceuticals | Purinové L-nukleosidy a jejich analogy a farmaceutické prostředky, které je obsahují |
| NZ335000A (en) * | 1996-10-28 | 2000-12-22 | Univ Washington | Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA |
| US6248878B1 (en) | 1996-12-24 | 2001-06-19 | Ribozyme Pharmaceuticals, Inc. | Nucleoside analogs |
| US6172046B1 (en) * | 1997-09-21 | 2001-01-09 | Schering Corporation | Combination therapy for eradicating detectable HCV-RNA in patients having chronic Hepatitis C infection |
| EP1317929A3 (en) | 1997-09-21 | 2003-07-02 | Schering Corporation | Combination therapy for eradicating detectable HCV-RNA in patients having chronic hepatitis c infection |
| US6472373B1 (en) | 1997-09-21 | 2002-10-29 | Schering Corporation | Combination therapy for eradicating detectable HCV-RNA in antiviral treatment naive patients having chronic hepatitis C infection |
| KR100263166B1 (ko) * | 1997-09-30 | 2000-08-01 | 윤종용 | 촬영신호 전송방법 및 전송장치 |
| DE69828702T2 (de) | 1997-10-30 | 2006-05-11 | The Government of the United States of America, as represented by the Secretary National Institute of Health, Office of Technology Transfer | Antitumorale uridinderivate |
| KR100719606B1 (ko) | 1998-02-25 | 2007-05-17 | 에모리 유니버시티 | 2'-플루오로뉴클레오사이드 |
| KR100389853B1 (ko) * | 1998-03-06 | 2003-08-19 | 삼성전자주식회사 | 카타로그정보의기록및재생방법 |
| AU767599B2 (en) | 1998-03-06 | 2003-11-20 | Metabasis Therapeutics, Inc. | Novel prodrugs for phosphorus-containing compounds |
| US6312662B1 (en) * | 1998-03-06 | 2001-11-06 | Metabasis Therapeutics, Inc. | Prodrugs phosphorus-containing compounds |
| EP1213029A1 (en) | 1998-05-15 | 2002-06-12 | Schering Corporation | Combination therapy for eradicating detectable HCV-RNA in antiviral treatment naive patients having chronic hepatitis C infection |
| US6833361B2 (en) | 1998-05-26 | 2004-12-21 | Ribapharm, Inc. | Nucleosides having bicyclic sugar moiety |
| DK1087778T3 (da) | 1998-06-08 | 2005-12-19 | Hoffmann La Roche | Anvendelse af PEG-IFN-alfa og Ribavirin til behandling af kronisk hepatitis C |
| US6444652B1 (en) | 1998-08-10 | 2002-09-03 | Novirio Pharmaceuticals Limited | β-L-2'-deoxy-nucleosides for the treatment of hepatitis B |
| DE69929060T2 (de) | 1998-08-10 | 2006-08-31 | Idenix (Cayman) Ltd. | Beta-l-2'-deoxynukleoside für die behandlung von hepatitis b virus |
| CN1324212A (zh) * | 1998-09-25 | 2001-11-28 | 维洛药品公司 | 治疗或预防病毒感染及有关疾病的方法 |
| US6277830B1 (en) * | 1998-10-16 | 2001-08-21 | Schering Corporation | 5′-amino acid esters of ribavirin and the use of same to treat hepatitis C with interferon |
| CA2252144A1 (en) | 1998-10-16 | 2000-04-16 | University Of Alberta | Dual action anticancer prodrugs |
| FR2784892B1 (fr) | 1998-10-23 | 2001-04-06 | Smith & Nephew Kinetec Sa | Attelle de mobilisation passive repliable pour membre inferieur |
| CN1216893C (zh) | 1998-11-05 | 2005-08-31 | 法国国家科学研究中心 | 具有抗乙型肝炎病毒活性的核苷 |
| KR100679239B1 (ko) | 1998-11-05 | 2007-02-07 | 쌍트르 나쉬오날 드 라 르쉐르스 쉬앙티피끄 | ＨＩＶ 감염 치료용 β-Ｌ-2'-데옥시-뉴클레오시드 |
| CA2354536A1 (en) | 1998-12-18 | 2000-06-29 | Schering Corporation | Ribavirin-pegylated interferon alfa induction hcv combination therapy |
| EP1155017B1 (en) * | 1999-02-22 | 2003-01-15 | Shire Biochem Inc. | [1,8] naphthyridine derivatives having antiviral activity |
| DE19908514A1 (de) | 1999-02-26 | 2000-09-21 | Fraunhofer Ges Forschung | Vorrichtung und Verfahren zur Lichtintensitätsmodulation |
| MXPA01008937A (es) | 1999-03-05 | 2004-04-05 | Metabasis Therapeutics Inc | Nuevos profarmacos que contienen fosforo. |
| US6831069B2 (en) | 1999-08-27 | 2004-12-14 | Ribapharm Inc. | Pyrrolo[2,3-d]pyrimidine nucleoside analogs |
| JP4979866B2 (ja) | 1999-09-08 | 2012-07-18 | リガンド・ファーマシューティカルズ・インコーポレイテッド | 肝臓に特異的なドラッグデリバリーのためのプロドラッグ |
| AU1262001A (en) | 1999-11-04 | 2001-05-14 | Biochem Pharma Inc. | Method for the treatment or prevention of flaviviridae viral infection using nucleoside analogues |
| MXPA02006156A (es) | 1999-12-22 | 2003-09-22 | Metabasis Therapeutics Inc | Nuevos profarmacos de bisamidato fosfonato. |
| US7056895B2 (en) | 2000-02-15 | 2006-06-06 | Valeant Pharmaceuticals International | Tirazole nucleoside analogs and methods for using same |
| US6455508B1 (en) | 2000-02-15 | 2002-09-24 | Kanda S. Ramasamy | Methods for treating diseases with tirazole and pyrrolo-pyrimidine ribofuranosyl nucleosides |
| US6495677B1 (en) | 2000-02-15 | 2002-12-17 | Kanda S. Ramasamy | Nucleoside compounds |
| CN1427722A (zh) | 2000-02-18 | 2003-07-02 | 希拉生物化学股份有限公司 | 用核苷类似物治疗或预防黄病毒感染的方法 |
| US7094770B2 (en) * | 2000-04-13 | 2006-08-22 | Pharmasset, Ltd. | 3′-or 2′-hydroxymethyl substituted nucleoside derivatives for treatment of hepatitis virus infections |
| EP1282632A1 (en) | 2000-04-20 | 2003-02-12 | Schering Corporation | Ribavirin-interferon alfa combination therapy for eradicating detectable hcv-rna in patients having chronic hepatitis c infection |
| MY164523A (en) * | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| US6787526B1 (en) | 2000-05-26 | 2004-09-07 | Idenix Pharmaceuticals, Inc. | Methods of treating hepatitis delta virus infection with β-L-2′-deoxy-nucleosides |
| EA007867B1 (ru) | 2000-05-26 | 2007-02-27 | Айденикс (Кайман) Лимитед | Композиции для лечения флавивирусных и пестивирусных инфекций и способы их применения |
| CN100490818C (zh) | 2000-05-26 | 2009-05-27 | 诺瓦蒂斯有限公司 | β-L-2′-脱氧核苷在制备用于治疗丁型肝炎病毒感染的药物中的用途 |
| US6875751B2 (en) | 2000-06-15 | 2005-04-05 | Idenix Pharmaceuticals, Inc. | 3′-prodrugs of 2′-deoxy-β-L-nucleosides |
| MY141594A (en) * | 2000-06-15 | 2010-05-14 | Novirio Pharmaceuticals Ltd | 3'-PRODRUGS OF 2'-DEOXY-ß-L-NUCLEOSIDES |
| US6815542B2 (en) | 2000-06-16 | 2004-11-09 | Ribapharm, Inc. | Nucleoside compounds and uses thereof |
| US6403584B1 (en) * | 2000-06-22 | 2002-06-11 | Merck & Co., Inc. | Substituted nipecotyl derivatives as inhibitors of cell adhesion |
| UA72612C2 (en) | 2000-07-06 | 2005-03-15 | Pyrido[2.3-d]pyrimidine and pyrimido[4.5-d]pyrimidine nucleoside analogues, prodrugs and method for inhibiting growth of neoplastic cells | |
| US20030008841A1 (en) * | 2000-08-30 | 2003-01-09 | Rene Devos | Anti-HCV nucleoside derivatives |
| CA2318667C (en) * | 2000-09-11 | 2004-02-24 | Fci Canada Inc. | Monolithic semiconductor photo-coupler incorporating an optical fiber alignment groove |
| ES2402597T3 (es) | 2000-10-18 | 2013-05-07 | Gilead Pharmasset Llc | Nucleósidos modificados para el tratamiento de infecciones víricas y proliferación celular anormal |
| JP2004511513A (ja) | 2000-10-18 | 2004-04-15 | シェリング・コーポレーション | リバビリン−ＰＥＧ化インターフェロンαＨＣＶ併用治療 |
| EP1360325A2 (en) * | 2000-10-18 | 2003-11-12 | Pharmasset Limited | Multiplex quantification of nucleic acids in diseased cells |
| CA2429352A1 (en) | 2000-12-15 | 2002-06-20 | Lieven Stuyver | Antiviral agents for treatment of flaviviridae infections |
| SI1355916T1 (sl) | 2001-01-22 | 2007-04-30 | Merck & Co Inc | Nukleozidni derivati kot inhibitorji RNA-odvisne RNA virusne polimeraze |
| US7105499B2 (en) * | 2001-01-22 | 2006-09-12 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| US6669805B2 (en) * | 2001-02-16 | 2003-12-30 | International Business Machines Corporation | Drill stack formation |
| CA2439836A1 (en) | 2001-03-01 | 2002-09-12 | Pharmasset Ltd. | Method for the synthesis of 2',3'-dideoxy-2',3'-didehydronucleosides |
| GB0112617D0 (en) | 2001-05-23 | 2001-07-18 | Hoffmann La Roche | Antiviral nucleoside derivatives |
| GB0114286D0 (en) | 2001-06-12 | 2001-08-01 | Hoffmann La Roche | Nucleoside Derivatives |
| US6949522B2 (en) | 2001-06-22 | 2005-09-27 | Pharmasset, Inc. | β-2′- or 3′-halonucleosides |
| WO2003024461A1 (en) | 2001-09-20 | 2003-03-27 | Schering Corporation | Hcv combination therapy |
| JP2005504087A (ja) | 2001-09-28 | 2005-02-10 | イデニクス（ケイマン）リミテツド | ４’が修飾されたヌクレオシドを使用するｃ型肝炎ウイルス治療のための方法および組成物 |
| US20040006002A1 (en) | 2001-09-28 | 2004-01-08 | Jean-Pierre Sommadossi | Methods and compositions for treating flaviviruses and pestiviruses using 4'-modified nucleoside |
| AU2002351077A1 (en) | 2001-11-05 | 2003-05-19 | Exiqon A/S | Oligonucleotides modified with novel alpha-l-rna analogues |
| MXPA04005779A (es) | 2001-12-14 | 2005-05-16 | Pharmasset Ltd | Nucleosidos de n4-acilcitosina para el tratamiento de infecciones virales. |
| AU2002353165A1 (en) | 2001-12-17 | 2003-06-30 | Ribapharm Inc. | Deazapurine nucleoside libraries and compounds |
| US6965066B1 (en) | 2002-01-16 | 2005-11-15 | Actodyne General, Inc. | Elongated string support for a stringed musical instrument |
| WO2003061385A1 (en) | 2002-01-17 | 2003-07-31 | Ribapharm Inc. | Tricyclic nucleoside library compounds, synthesis, and use as antiviral agents |
| WO2003062256A1 (en) | 2002-01-17 | 2003-07-31 | Ribapharm Inc. | 2'-beta-modified-6-substituted adenosine analogs and their use as antiviral agents |
| WO2003062255A2 (en) | 2002-01-17 | 2003-07-31 | Ribapharm Inc. | Sugar modified nucleosides as viral replication inhibitors |
| US20040010717A1 (en) * | 2002-01-29 | 2004-01-15 | Intertainer Asia Pte Ltd. | Apparatus and method for preventing digital media piracy |
| US7323453B2 (en) | 2002-02-13 | 2008-01-29 | Merck & Co., Inc. | Methods of inhibiting orthopoxvirus replication with nucleoside compounds |
| US20040002476A1 (en) | 2002-02-14 | 2004-01-01 | Stuyver Lieven J. | Modified fluorinated nucleoside analogues |
| WO2003072757A2 (en) | 2002-02-28 | 2003-09-04 | Biota, Inc. | Nucleotide mimics and their prodrugs |
| US7247621B2 (en) | 2002-04-30 | 2007-07-24 | Valeant Research & Development | Antiviral phosphonate compounds and methods therefor |
| MXPA04010983A (es) * | 2002-05-06 | 2005-02-14 | Genelabs Tech Inc | Derivados de nucleosidos para tratar infecciones por el virus de la hepatitis c. |
| AU2003241621A1 (en) | 2002-05-24 | 2003-12-12 | Isis Pharmaceuticals, Inc. | Oligonucleotides having modified nucleoside units |
| US20040014957A1 (en) | 2002-05-24 | 2004-01-22 | Anne Eldrup | Oligonucleotides having modified nucleoside units |
| DE10226932A1 (de) | 2002-06-17 | 2003-12-24 | Bayer Ag | Strahlenhärtende Beschichtungsmittel |
| WO2003105770A2 (en) | 2002-06-17 | 2003-12-24 | Merck & Co., Inc. | Carbocyclic nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| AU2003269890A1 (en) | 2002-06-21 | 2004-01-06 | Isis Pharmaceuticals, Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| AU2003269892A1 (en) | 2002-06-27 | 2004-01-19 | Isis Pharmaceuticals, Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| EP2799442A1 (en) | 2002-06-28 | 2014-11-05 | IDENIX Pharmaceuticals, Inc. | Modified 2' and 3' -nucleoside prodrugs for treating flaviridae infections |
| JP5087211B2 (ja) | 2002-06-28 | 2012-12-05 | イデニクス（ケイマン）リミテツド | フラビウィルス感染治療のための２′および３′−ヌクレオシドプロドラッグ |
| MXPA04012802A (es) | 2002-06-28 | 2005-04-19 | Idenix Cayman Ltd | Ester 2'-c-metil-3'-o-l-valina de ribofuranosil-citidina para el tratamiento de infecciones por flaviviridae. |
| WO2004007512A2 (en) | 2002-07-16 | 2004-01-22 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| WO2004009020A2 (en) | 2002-07-24 | 2004-01-29 | Merck & Co., Inc. | Pyrrolopyrimidine thionucleoside analogs as antivirals |
| NZ538457A (en) | 2002-09-30 | 2008-04-30 | Genelabs Tech Inc | Nucleoside derivatives for treating hepatitis C virus infection |
| US7094768B2 (en) * | 2002-09-30 | 2006-08-22 | Genelabs Technologies, Inc. | Nucleoside derivatives for treating hepatitis C virus infection |
| AU2003295388A1 (en) | 2002-11-05 | 2004-06-03 | Isis Pharmaceuticals, Inc. | 2'-substituted oligomeric compounds and compositions for use in gene modulations |
| WO2004044133A2 (en) | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Modified oligonucleotides for use in rna interference |
| EP1576138B1 (en) | 2002-11-15 | 2017-02-01 | Idenix Pharmaceuticals LLC. | 2'-methyl nucleosides in combination with interferon and flaviviridae mutation |
| TWI332507B (en) | 2002-11-19 | 2010-11-01 | Hoffmann La Roche | Antiviral nucleoside derivatives |
| CA2509687C (en) | 2002-12-12 | 2012-08-14 | Idenix (Cayman) Limited | Process for the production of 2'-branched nucleosides |
| US20040181051A1 (en) | 2002-12-23 | 2004-09-16 | Richard Storer | Process for the production of 3'-nucleoside prodrugs |
| WO2004065398A2 (en) | 2003-01-15 | 2004-08-05 | Ribapharm Inc. | Synthesis and use of 2'-substituted-n6-modified nucleosides |
| AR043006A1 (es) | 2003-02-12 | 2005-07-13 | Merck & Co Inc | Proceso para preparar ribonucleosidos ramificados |
| WO2004080466A1 (en) | 2003-03-07 | 2004-09-23 | Ribapharm Inc. | Cytidine analogs and methods of use |
| BRPI0408561A (pt) | 2003-03-20 | 2006-03-21 | Microbiol Quimica Farmaceutica | métodos para manufatura de 2'-desoxi-59-l-nucleosìeos |
| WO2004084796A2 (en) | 2003-03-28 | 2004-10-07 | Pharmasset Ltd. | Compounds for the treatment of flaviviridae infections |
| EP1620451A4 (en) | 2003-04-28 | 2009-02-18 | Novartis Ag | TO THE MOST EXTENSIVE NUCLEOSIDE SYNTHESIS |
| US20040259934A1 (en) | 2003-05-01 | 2004-12-23 | Olsen David B. | Inhibiting Coronaviridae viral replication and treating Coronaviridae viral infection with nucleoside compounds |
| US20040229839A1 (en) | 2003-05-14 | 2004-11-18 | Biocryst Pharmaceuticals, Inc. | Substituted nucleosides, preparation thereof and use as inhibitors of RNA viral polymerases |
| EP1656093A2 (en) | 2003-05-14 | 2006-05-17 | Idenix (Cayman) Limited | Nucleosides for treatment of infection by corona viruses, toga viruses and picorna viruses |
| WO2005020885A2 (en) | 2003-05-21 | 2005-03-10 | Isis Pharmaceuticals, Inc. | Compositions and methods for the treatment of severe acute respiratory syndrome (sars) |
| WO2004106356A1 (en) | 2003-05-27 | 2004-12-09 | Syddansk Universitet | Functionalized nucleotide derivatives |
| ES2726998T3 (es) | 2003-05-30 | 2019-10-11 | Gilead Pharmasset Llc | Análogos de nucleósidos fluorados modificados |
| KR20060026426A (ko) | 2003-06-19 | 2006-03-23 | 에프. 호프만-라 로슈 아게 | 4'-아지도 뉴클레오사이드 유도체의 제조 방법 |
| GB0317009D0 (en) | 2003-07-21 | 2003-08-27 | Univ Cardiff | Chemical compounds |
| ATE486883T1 (de) | 2003-08-27 | 2010-11-15 | Biota Scient Management | Neue tricyclische nukleoside oder nukleotide als therapeutische mittel |
| JP2007522094A (ja) | 2003-09-22 | 2007-08-09 | アシドフィル エルエルシー | 小分子組成物、及びその組成物を使用して薬物効率を高めるための方法 |
| US7151089B2 (en) * | 2003-10-27 | 2006-12-19 | Genelabs Technologies, Inc. | Nucleoside compounds for treating viral infections |
| US20050137141A1 (en) | 2003-10-24 | 2005-06-23 | John Hilfinger | Prodrug composition |
| KR20060096487A (ko) * | 2003-10-27 | 2006-09-11 | 진랩스 테크놀러지스, 인크. | 바이러스 감염증들을 치료하기 위한 뉴클레오시드 화합물 |
| WO2005054268A1 (en) | 2003-10-27 | 2005-06-16 | Genelabs Technologies, Inc. | Nucleoside compounds for treating viral infections |
| WO2006016930A2 (en) | 2004-05-14 | 2006-02-16 | Intermune, Inc. | Methods for treating hcv infection |
| JP5055564B2 (ja) | 2004-06-15 | 2012-10-24 | メルク・シャープ・エンド・ドーム・コーポレイション | Ｒｎａ依存性ｒｎａウイルスポリメラーゼの阻害剤としてのｃ−プリンヌクレオシド類似体 |
| WO2006002231A1 (en) | 2004-06-22 | 2006-01-05 | Biocryst Pharmaceuticals, Inc. | Aza nucleosides, preparation thereof and use as inhibitors of rna viral polymerases |
| CA2571079A1 (en) | 2004-06-24 | 2006-02-02 | Merck & Co., Inc. | Nucleoside aryl phosphoramidates for the treatment of rna-dependent rna viral infection |
| CN101023094B (zh) | 2004-07-21 | 2011-05-18 | 法莫赛特股份有限公司 | 烷基取代的2-脱氧-2-氟代-d-呋喃核糖基嘧啶和嘌呤及其衍生物的制备 |
| DK1773856T3 (da) | 2004-07-21 | 2012-05-21 | Gilead Pharmasset Llc | Fremstilling af alkylsubstituerede 2-desoxy-2-fluor-D-ribofuranosylpyrimidiner og -puriner og derivater deraf |
| DE602005015466D1 (de) | 2004-08-23 | 2009-08-27 | Hoffmann La Roche | Antivirale 4'-azidonucleoside |
| US7544632B2 (en) * | 2004-09-22 | 2009-06-09 | Exxonmobil Research And Engineering Company | Bulk Ni-Mo-W catalysts made from precursors containing an organic agent |
| KR20070073805A (ko) | 2004-09-24 | 2007-07-10 | 이데닉스 (케이만) 리미티드 | 플라비바이러스, 페스티바이러스 및 헤파시바이러스를치료하기 위한 방법 및 조성물 |
| EP1802327A4 (en) | 2004-10-06 | 2009-07-15 | Migenix Inc | COMBINED ANTIVIRAL COMPOSITIONS WITH CASTANOSPERMIN AND METHOD OF USE |
| AU2005317081A1 (en) | 2004-10-21 | 2006-06-22 | Merck & Co., Inc. | Fluorinated pyrrolo[2,3-d]pyrimidine nucleosides for the treatment of RNA-dependent RNA viral infection |
| WO2006121468A1 (en) | 2004-11-22 | 2006-11-16 | Genelabs Technologies, Inc. | 5-nitro-nucleoside compounds for treating viral infections |
| WO2006063717A2 (en) | 2004-12-16 | 2006-06-22 | Febit Biotech Gmbh | Polymerase-independent analysis of the sequence of polynucleotides |
| EA200701669A1 (ru) | 2005-02-09 | 2008-02-28 | Мидженикс Инк. | Композиции и способы лечения или предотвращения инфекций, вызванных вирусами семейства flaviviridae |
| DE102005012681A1 (de) | 2005-03-18 | 2006-09-21 | Weber, Lutz, Dr. | Neue 1,5-Dihydro-pyrrol-2-one |
| WO2006097323A1 (en) | 2005-03-18 | 2006-09-21 | Lutz Weber | TETRAHYDRO-ISOQUINOLIN-l-ONES FOR THE TREATMENT OF CANCER |
| GT200600119A (es) | 2005-03-24 | 2006-10-25 | Composiciones farmaceuticas | |
| US7405204B2 (en) | 2005-04-25 | 2008-07-29 | Genelabs Technologies, Inc. | Nucleoside compounds for treating viral infections |
| WO2006121820A1 (en) | 2005-05-05 | 2006-11-16 | Valeant Research & Development | Phosphoramidate prodrugs for treatment of viral infection |
| AU2006252718B2 (en) | 2005-05-31 | 2010-04-15 | Novartis Ag | Treatment of liver diseases in which iron plays a role in pathogenesis |
| EP1909564A4 (en) | 2005-07-18 | 2010-06-30 | Novartis Ag | SMALL ANIMAL MODEL FOR HCV REPLICATION |
| AR057096A1 (es) | 2005-08-26 | 2007-11-14 | Chancellors Masters And Schola | Proceso para preparar acidos y lactonas sacarinicos |
| US7781576B2 (en) | 2005-12-23 | 2010-08-24 | Idenix Pharmaceuticals, Inc. | Process for preparing a synthetic intermediate for preparation of branched nucleosides |
-
2003
- 2003-06-27 MX MXPA04012802A patent/MXPA04012802A/es not_active Application Discontinuation
- 2003-06-27 KR KR1020047021073A patent/KR20050035194A/ko not_active Ceased
- 2003-06-27 JP JP2004518041A patent/JP2005533824A/ja active Pending
- 2003-06-27 AU AU2003248748A patent/AU2003248748A1/en not_active Abandoned
- 2003-06-27 US US10/607,909 patent/US7456155B2/en not_active Expired - Lifetime
- 2003-06-27 AP AP2005003213A patent/AP2005003213A0/xx unknown
- 2003-06-27 PL PL03374781A patent/PL374781A1/xx not_active Application Discontinuation
- 2003-06-27 CN CNA03820701XA patent/CN1678326A/zh active Pending
- 2003-06-27 BR BRPI0312278-6A patent/BR0312278A/pt not_active IP Right Cessation
- 2003-06-27 CA CA002489552A patent/CA2489552A1/en not_active Abandoned
- 2003-06-27 RS YUP-1139/04A patent/RS113904A/sr unknown
- 2003-06-27 EP EP03762183A patent/EP1536804A4/en not_active Withdrawn
- 2003-06-27 US US10/609,298 patent/US7662798B2/en not_active Expired - Fee Related
- 2003-06-27 WO PCT/US2003/020431 patent/WO2004002422A2/en not_active Ceased
-
2004
- 2004-12-06 US US11/005,444 patent/US7625875B2/en not_active Expired - Fee Related
- 2004-12-06 US US11/005,472 patent/US20070060505A1/en not_active Abandoned
- 2004-12-06 US US11/005,446 patent/US20070060504A1/en not_active Abandoned
- 2004-12-06 US US11/005,466 patent/US20070060541A1/en not_active Abandoned
- 2004-12-06 US US11/005,442 patent/US20070037735A1/en not_active Abandoned
- 2004-12-06 US US11/005,440 patent/US20070060503A1/en not_active Abandoned
- 2004-12-06 US US11/005,471 patent/US20070042990A1/en not_active Abandoned
-
2005
- 2005-01-25 MA MA28070A patent/MA27374A1/fr unknown
- 2005-01-27 NO NO20050490A patent/NO20050490L/no not_active Application Discontinuation
-
2014
- 2014-08-07 LU LU92513C patent/LU92513I2/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20070037735A1 (en) | 2007-02-15 |
| US20070015905A1 (en) | 2007-01-18 |
| WO2004002422A3 (en) | 2005-04-07 |
| RS113904A (sr) | 2007-02-05 |
| BR0312278A (pt) | 2007-06-19 |
| JP2005533824A (ja) | 2005-11-10 |
| LU92513I2 (fr) | 2015-11-02 |
| US7662798B2 (en) | 2010-02-16 |
| MA27374A1 (fr) | 2005-06-01 |
| WO2004002422A2 (en) | 2004-01-08 |
| AP2005003213A0 (en) | 2005-03-31 |
| US20070060505A1 (en) | 2007-03-15 |
| AU2003248748A1 (en) | 2004-01-19 |
| KR20050035194A (ko) | 2005-04-15 |
| CN1678326A (zh) | 2005-10-05 |
| US20070060504A1 (en) | 2007-03-15 |
| EP1536804A4 (en) | 2007-10-31 |
| US20040077587A1 (en) | 2004-04-22 |
| NO20050490L (no) | 2005-01-27 |
| US20070042990A1 (en) | 2007-02-22 |
| US20070060541A1 (en) | 2007-03-15 |
| US20070060498A1 (en) | 2007-03-15 |
| US7625875B2 (en) | 2009-12-01 |
| US20070060503A1 (en) | 2007-03-15 |
| PL374781A1 (en) | 2005-10-31 |
| CA2489552A1 (en) | 2004-01-08 |
| EP1536804A2 (en) | 2005-06-08 |
| US7456155B2 (en) | 2008-11-25 |
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