DE60215157T2 - Verwendungen von antiviralen nucleosid-derivaten zur herstellung eines medikaments zur behandlung von hepatitis c infektionen - Google Patents
Verwendungen von antiviralen nucleosid-derivaten zur herstellung eines medikaments zur behandlung von hepatitis c infektionen Download PDFInfo
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- DE60215157T2 DE60215157T2 DE60215157T DE60215157T DE60215157T2 DE 60215157 T2 DE60215157 T2 DE 60215157T2 DE 60215157 T DE60215157 T DE 60215157T DE 60215157 T DE60215157 T DE 60215157T DE 60215157 T2 DE60215157 T2 DE 60215157T2
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- hcv
- hepatitis
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- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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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
- A61K31/70—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
- A61K31/7076—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 containing purines, e.g. adenosine, adenylic acid
-
- 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
- A61K31/70—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
-
- 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
- A61K31/70—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
- A61K31/7076—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 containing purines, e.g. adenosine, adenylic acid
- A61K31/708—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 containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0112617.6A GB0112617D0 (en) | 2001-05-23 | 2001-05-23 | Antiviral nucleoside derivatives |
| GB0112617 | 2001-05-23 | ||
| PCT/EP2002/005340 WO2002094289A1 (en) | 2001-05-23 | 2002-05-15 | Antiviral nucleoside derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60215157D1 DE60215157D1 (de) | 2006-11-16 |
| DE60215157T2 true DE60215157T2 (de) | 2007-08-23 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60215157T Expired - Lifetime DE60215157T2 (de) | 2001-05-23 | 2002-05-15 | Verwendungen von antiviralen nucleosid-derivaten zur herstellung eines medikaments zur behandlung von hepatitis c infektionen |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6660721B2 (OSRAM) |
| EP (1) | EP1395266B1 (OSRAM) |
| JP (1) | JP2004534769A (OSRAM) |
| CA (1) | CA2445744C (OSRAM) |
| DE (1) | DE60215157T2 (OSRAM) |
| ES (1) | ES2272732T3 (OSRAM) |
| GB (1) | GB0112617D0 (OSRAM) |
| WO (1) | WO2002094289A1 (OSRAM) |
Families Citing this family (104)
| Publication number | Priority date | Publication date | Assignee | Title |
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| ATE414520T1 (de) * | 2000-04-13 | 2008-12-15 | Pharmasset Inc | 3 oder 2 hydroxymethyl substituierte nucleoside derivate und ihre verwendung zur behandlung von virusinfektionen |
| 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 |
| 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 |
| US8481712B2 (en) | 2001-01-22 | 2013-07-09 | Merck Sharp & Dohme Corp. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| 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 |
| 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 |
| 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 |
| US7608600B2 (en) | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| US20040067877A1 (en) * | 2002-08-01 | 2004-04-08 | Schinazi Raymond F. | 2', 3'-Dideoxynucleoside analogues for the treatment or prevention of Flaviviridae infections |
| MXPA05001298A (es) * | 2002-08-01 | 2005-11-04 | Pharmasset Inc | Compuestos con el sistema biciclo[4.2.1] nonano para el tratamiento de infecciones por flaviviridae. |
| 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 |
| CN100528167C (zh) | 2002-10-23 | 2009-08-19 | 潘塔希生物科学股份有限公司 | 用于治疗癌症的包含雌四醇衍生物的药物组合物 |
| 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 |
| BR0316868A (pt) * | 2002-12-23 | 2005-10-25 | Idenix Cayman Ltd | Processo para a produção de pró-medicamentos de nucleosìdeo-3' |
| US20050049204A1 (en) * | 2003-03-28 | 2005-03-03 | Otto Michael J. | Compounds for the treatment of flaviviridae infections |
| SI2604620T2 (sl) | 2003-05-30 | 2024-10-30 | Gilead Pharmasset Llc | Modificirani fluorirani nukleozidni analogi |
| US20050075309A1 (en) | 2003-07-25 | 2005-04-07 | Richard Storer | Purine nucleoside analogues for treating Flaviviridae including hepatitis C |
| WO2005018330A1 (en) * | 2003-08-18 | 2005-03-03 | Pharmasset, Inc. | Dosing regimen for flaviviridae therapy |
| KR20120091276A (ko) | 2004-02-20 | 2012-08-17 | 베링거 인겔하임 인터내셔날 게엠베하 | 바이러스 폴리머라제 억제제 |
| US20060040944A1 (en) * | 2004-06-23 | 2006-02-23 | Gilles Gosselin | 5-Aza-7-deazapurine derivatives for treating Flaviviridae |
| AU2005267421B2 (en) * | 2004-06-24 | 2010-06-03 | Merck Sharp & Dohme Corp. | 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 |
| US8492539B2 (en) | 2004-09-14 | 2013-07-23 | Gilead Pharmasset Llc | Preparation of 2′-fluoro-2′-alkyl-substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives |
| US20080280842A1 (en) * | 2004-10-21 | 2008-11-13 | Merck & Co., Inc. | Fluorinated Pyrrolo[2,3-D]Pyrimidine Nucleosides for the Treatment of Rna-Dependent Rna Viral Infection |
| US7524831B2 (en) | 2005-03-02 | 2009-04-28 | Schering Corporation | Treatments for Flaviviridae virus infection |
| JP4516863B2 (ja) * | 2005-03-11 | 2010-08-04 | 株式会社ケンウッド | 音声合成装置、音声合成方法及びプログラム |
| WO2007075876A2 (en) * | 2005-12-23 | 2007-07-05 | Idenix Pharmaceuticals, Inc. | Process for preparing a synthetic intermediate for preparation of branched nucleosides |
| US20080261913A1 (en) | 2006-12-28 | 2008-10-23 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of liver disorders |
| EP2124555B1 (en) * | 2007-01-05 | 2015-07-08 | Merck Sharp & Dohme Corp. | Nucleoside aryl phosphoramidates for the treatment of rna-dependent rna viral infection |
| PL2144604T3 (pl) | 2007-02-28 | 2012-02-29 | Conatus Pharmaceuticals Inc | Sposoby leczenia przewlekłego zapalenia wątroby typu C z zastosowaniem RO 113-0830 |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| EP2307434B1 (en) * | 2008-07-02 | 2014-02-12 | IDENIX Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of viral infections |
| PA8855601A1 (es) | 2008-12-23 | 2010-07-27 | Forformidatos de nucleósidos | |
| US8716263B2 (en) | 2008-12-23 | 2014-05-06 | Gilead Pharmasset Llc | Synthesis of purine nucleosides |
| US8551973B2 (en) | 2008-12-23 | 2013-10-08 | Gilead Pharmasset Llc | Nucleoside analogs |
| JP5690286B2 (ja) | 2009-03-04 | 2015-03-25 | イデニク プハルマセウティカルス,インコーポレイテッド | ホスホチオフェン及びホスホチアゾールhcvポリメラーゼ阻害剤 |
| TWI598358B (zh) | 2009-05-20 | 2017-09-11 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
| US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| JP2013501068A (ja) | 2009-08-05 | 2013-01-10 | アイディニックス ファーマシューティカルズ インコーポレイテッド | 大環状セリンプロテアーゼ阻害剤 |
| US20110117055A1 (en) | 2009-11-19 | 2011-05-19 | Macdonald James E | Methods of Treating Hepatitis C Virus with Oxoacetamide Compounds |
| US8362068B2 (en) | 2009-12-18 | 2013-01-29 | Idenix Pharmaceuticals, Inc. | 5,5-fused arylene or heteroarylene hepatitis C virus inhibitors |
| WO2011123668A2 (en) | 2010-03-31 | 2011-10-06 | Pharmasset, Inc. | Stereoselective synthesis of phosphorus containing actives |
| PL3290428T3 (pl) | 2010-03-31 | 2022-02-07 | Gilead Pharmasset Llc | Tabletka zawierająca krystaliczny (S)-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 izopropylu |
| WO2011123586A1 (en) | 2010-04-01 | 2011-10-06 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of viral infections |
| EP2646453A1 (en) | 2010-11-30 | 2013-10-09 | Gilead Pharmasset LLC | Compounds |
| WO2012080050A1 (en) | 2010-12-14 | 2012-06-21 | F. Hoffmann-La Roche Ag | Solid forms of a phenoxybenzenesulfonyl compound |
| TW201309690A (zh) | 2011-02-10 | 2013-03-01 | Idenix Pharmaceuticals Inc | 巨環絲胺酸蛋白酶抑制劑,其醫藥組合物及其於治療hcv感染之用途 |
| 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 |
| EP2691409B1 (en) | 2011-03-31 | 2018-02-21 | Idenix Pharmaceuticals LLC. | Compounds and pharmaceutical compositions for the treatment of viral infections |
| 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 |
| 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 |
| 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 |
| AR088441A1 (es) | 2011-09-12 | 2014-06-11 | Idenix Pharmaceuticals Inc | Compuestos de carboniloximetilfosforamidato sustituido y composiciones farmaceuticas para el tratamiento de infecciones virales |
| AU2012308900A1 (en) | 2011-09-12 | 2013-05-09 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of viral infections |
| SMT201800087T1 (it) | 2011-09-16 | 2018-03-08 | Gilead Pharmasset Llc | Metodi per trattare hcv |
| EP2768838A1 (en) | 2011-10-14 | 2014-08-27 | IDENIX Pharmaceuticals, Inc. | Substituted 3',5'-cyclic phosphates of purine nucleotide compounds and pharmaceutical compositions for the treatment of viral infections |
| US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
| US9089574B2 (en) | 2011-11-30 | 2015-07-28 | Emory University | Antiviral JAK inhibitors useful in treating or preventing retroviral and other viral infections |
| US20130217644A1 (en) | 2012-02-13 | 2013-08-22 | Idenix Pharmaceuticals, Inc. | Pharmaceutical Compositions of 2'-C-Methyl-Guanosine, 5'-[2[(3-Hydroxy-2,2-Dimethyl-1-Oxopropyl)Thio]Ethyl N-(Phenylmethyl)Phosphoramidate] |
| KR102068856B1 (ko) * | 2012-03-13 | 2020-01-21 | 길리애드 사이언시즈, 인코포레이티드 | 항바이러스 치료를 위한 2'-치환된 카바-뉴클레오시드 유사체 |
| EP2852604B1 (en) | 2012-05-22 | 2017-04-12 | Idenix Pharmaceuticals LLC | 3',5'-cyclic phosphoramidate prodrugs for hcv infection |
| BR112014029115A8 (pt) | 2012-05-22 | 2018-04-03 | Idenix Pharmaceuticals Inc | Composto, composição farmacêutica, e, uso de um composto ou composição |
| EP2852605B1 (en) | 2012-05-22 | 2018-01-31 | Idenix Pharmaceuticals LLC | 3',5'-cyclic phosphate prodrugs for hcv infection |
| ES2597757T3 (es) | 2012-05-25 | 2017-01-20 | Janssen Sciences Ireland Uc | Nucleósidos de uracilespirooxetano |
| US9192621B2 (en) | 2012-09-27 | 2015-11-24 | Idenix Pharmaceuticals Llc | Esters and malonates of SATE prodrugs |
| BR112015007698A2 (pt) | 2012-10-08 | 2017-08-22 | Idenix Pharmaceuticals Inc Centre National De La Recherche Scientifique E Univ Montpellier 2 Science | Composto, composição farmacêutica, e, uso de um composto |
| WO2014063019A1 (en) | 2012-10-19 | 2014-04-24 | Idenix Pharmaceuticals, Inc. | Dinucleotide compounds for hcv infection |
| EP2909222B1 (en) | 2012-10-22 | 2021-05-26 | Idenix Pharmaceuticals LLC | 2',4'-bridged nucleosides for hcv infection |
| WO2014078436A1 (en) | 2012-11-14 | 2014-05-22 | Idenix Pharmaceuticals, Inc. | D-alanine ester of sp-nucleoside analog |
| WO2014078427A1 (en) | 2012-11-14 | 2014-05-22 | Idenix Pharmaceuticals, Inc. | D-alanine ester of rp-nucleoside analog |
| WO2014099941A1 (en) | 2012-12-19 | 2014-06-26 | Idenix Pharmaceuticals, Inc. | 4'-fluoro nucleosides for the treatment of hcv |
| EA029081B9 (ru) | 2013-01-31 | 2018-09-28 | Джилид Фармассет Ллс | Комбинированный состав двух противовирусных соединений |
| 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 |
| US10005779B2 (en) | 2013-06-05 | 2018-06-26 | Idenix Pharmaceuticals Llc | 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 |
| PL3038601T3 (pl) | 2013-08-27 | 2020-08-24 | Gilead Pharmasset Llc | Formulacja złożona dwóch związków przeciwwirusowych |
| WO2015042375A1 (en) | 2013-09-20 | 2015-03-26 | 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 |
| US20160271162A1 (en) | 2013-11-01 | 2016-09-22 | Idenix Pharmacueticals, Llc | D-alanine phosphoramide pronucleotides of 2'-methyl 2'-fluro guanosine nucleoside compounds for the treatment of hcv |
| EP3074399A1 (en) | 2013-11-27 | 2016-10-05 | Idenix Pharmaceuticals LLC | 2'-dichloro and 2'-fluoro-2'-chloro nucleoside analogues for hcv infection |
| US10683321B2 (en) | 2013-12-18 | 2020-06-16 | Idenix Pharmaceuticals Llc | 4′-or nucleosides for the treatment of HCV |
| EP3114122A1 (en) | 2014-03-05 | 2017-01-11 | Idenix Pharmaceuticals LLC | Solid forms of a flaviviridae virus inhibitor compound and salts thereof |
| WO2015134561A1 (en) | 2014-03-05 | 2015-09-11 | Idenix Pharmaceuticals, Inc. | Pharmaceutical compositions comprising a 5,5-fused heteroarylene flaviviridae inhibitor and their use for treating or preventing flaviviridae infection |
| WO2015161137A1 (en) | 2014-04-16 | 2015-10-22 | Idenix Pharmaceuticals, Inc. | 3'-substituted methyl or alkynyl nucleosides for the treatment of hcv |
| 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 |
| JP6857365B2 (ja) * | 2016-03-11 | 2021-04-14 | 国立大学法人 鹿児島大学 | 抗肝腫瘍ウイルス剤 |
| US10202412B2 (en) | 2016-07-08 | 2019-02-12 | Atea Pharmaceuticals, Inc. | β-D-2′-deoxy-2′-substituted-4′-substituted-2-substituted-N6-substituted-6-aminopurinenucleotides for the treatment of paramyxovirus and orthomyxovirus infections |
| 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 |
| 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 |
| 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 |
| JP2020125245A (ja) * | 2019-02-01 | 2020-08-20 | ダイキン工業株式会社 | 抗c型肝炎ウイルス剤 |
| US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
| 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 (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5587362A (en) | 1994-01-28 | 1996-12-24 | Univ. Of Ga Research Foundation | L-nucleosides |
| EA200700564A1 (ru) | 1998-02-25 | 2007-08-31 | Эмори Юниверсити | 2`-фторнуклеозиды |
| US5968826A (en) | 1998-10-05 | 1999-10-19 | Isis Pharmaceuticals Inc. | Antisense inhibition of integrin α4 expression |
| CA2426187C (en) | 2000-10-18 | 2011-08-16 | Pharmasset Limited | Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation |
-
2001
- 2001-05-23 GB GBGB0112617.6A patent/GB0112617D0/en not_active Ceased
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2002
- 2002-03-26 US US10/106,970 patent/US6660721B2/en not_active Expired - Fee Related
- 2002-05-15 CA CA002445744A patent/CA2445744C/en not_active Expired - Fee Related
- 2002-05-15 WO PCT/EP2002/005340 patent/WO2002094289A1/en not_active Ceased
- 2002-05-15 EP EP02743012A patent/EP1395266B1/en not_active Expired - Lifetime
- 2002-05-15 ES ES02743012T patent/ES2272732T3/es not_active Expired - Lifetime
- 2002-05-15 JP JP2002591006A patent/JP2004534769A/ja active Pending
- 2002-05-15 DE DE60215157T patent/DE60215157T2/de not_active Expired - Lifetime
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| JP2004534769A (ja) | 2004-11-18 |
| US6660721B2 (en) | 2003-12-09 |
| GB0112617D0 (en) | 2001-07-18 |
| US20030083307A1 (en) | 2003-05-01 |
| EP1395266B1 (en) | 2006-10-04 |
| CA2445744A1 (en) | 2002-11-28 |
| DE60215157D1 (de) | 2006-11-16 |
| WO2002094289A1 (en) | 2002-11-28 |
| CA2445744C (en) | 2007-12-04 |
| ES2272732T3 (es) | 2007-05-01 |
| EP1395266A1 (en) | 2004-03-10 |
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