WO2004058792A1 - Process for the production of 3'-nucleoside prodrugs - Google Patents

Process for the production of 3'-nucleoside prodrugs Download PDF

Info

Publication number
WO2004058792A1
WO2004058792A1 PCT/US2003/041603 US0341603W WO2004058792A1 WO 2004058792 A1 WO2004058792 A1 WO 2004058792A1 US 0341603 W US0341603 W US 0341603W WO 2004058792 A1 WO2004058792 A1 WO 2004058792A1
Authority
WO
WIPO (PCT)
Prior art keywords
nucleoside
free
protection
reaction
methyl branched
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2003/041603
Other languages
English (en)
French (fr)
Inventor
Richard Storer
Adel Moussa
Steven Mathieu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Idenix Cayman Ltd
Original Assignee
Idenix Cayman Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to AU2003300434A priority Critical patent/AU2003300434A1/en
Priority to NZ540913A priority patent/NZ540913A/en
Priority to MXPA05006865A priority patent/MXPA05006865A/es
Priority to BR0316868-9A priority patent/BR0316868A/pt
Priority to CA002511616A priority patent/CA2511616A1/en
Priority to JP2004562599A priority patent/JP2006514038A/ja
Application filed by Idenix Cayman Ltd filed Critical Idenix Cayman Ltd
Priority to EP03814400A priority patent/EP1575971A4/en
Publication of WO2004058792A1 publication Critical patent/WO2004058792A1/en
Priority to IL169314A priority patent/IL169314A0/en
Anticipated expiration legal-status Critical
Priority to NO20053557A priority patent/NO20053557L/no
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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

Definitions

  • any tertiary amine may replace TEA such as, for example, diisopropylethylamine and N-ethylmorpholine.
  • Solvents can consist of any polar aprotic solvent including, but not limiting to, acetone, ethyl acetate, dithianes, THF, dioxane, acetonitrile, dichloromethane, dichloroethane, diethyl ether, pyridine, dimethylformamide (DMF), DME, dimethylsulfoxide (DMSO), dimethylacetamide, or any combination thereof, though preferably DMF.
  • polar aprotic solvent including, but not limiting to, acetone, ethyl acetate, dithianes, THF, dioxane, acetonitrile, dichloromethane, dichloroethane, diethyl ether, pyridine, dimethylformamide (DMF), DME, dimethylsulfoxide (DMSO), dimethylacetamide, or any combination thereof, though preferably DMF.
  • the solution is neutralized with acetic acid to a p ⁇ of about 7.69, and DMF is removed under vacuum at a temperature of about 35 °C.
  • the solution is chased with ethyl acetate, and the crude product is stirred with ethyl acetate and water.
  • the two layers are separated, and again the aqueous layer is extracted with ethyl acetate.
  • the two organic layers are combined and washed with an aqueous saturated brine solution; the resulting organic layer is extracted with an aqueous solution of malonic acid.
  • the organic layer is checked by TLC (thin layer chromatography) to be certain that all the desired product has been removed.
  • the base is a pyrimidine base selected from the group consisting of thymine, cytosine, 5-fluorocytosine, 5-methylcytosine, 6-aza-pyrimidine, including 6-azacytosine, 2- and/or 4-mercaptopyrmidine, uracil, 5-halouracil, C 5 - alkylpyrimidines, C 5 -benzylpyrimidines, C 5 -halopyrimidines, C 5 -vinylpyrimidine,
  • the 2'-C- methyl branched nucleoside to be selectively esterified at the 3 '-position is
  • non-natural amino acid refers to a carboxylic acid having an amino group terminus but that is not found in nature.
  • the term is intended to embrace both D- and L-amino acids, and any tautomeric or stereoisomeric forms thereof.
  • C -aminopyrimidine N -alkylpurines, N -alkyl-6-thiopurines, 5-azacytidinyl, 5- azauracilyl, triazolopyridinyl, imidazolopyridinyl, pyrrolopyrimidinyl, and pyrazolo- pyrimidinyl.
  • Purine bases include, but are not limited to, guanine, adenine, hypoxanthine, 2,6-diaminopurine, and 6-chloropurine. Functional oxygen and nitrogen groups on the base can be protected as necessary or desired.
  • the process of the present invention is not limited to the use of BOC as a protecting group.
  • Other protecting groups such as, for example, substituted or unsubstituted silyl groups; substituted or unsubstituted ether groups like C-O-aralkyl, C-
  • Any organic solvents such as, for example, toluene may replace acetonitrile.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Saccharide Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
PCT/US2003/041603 2002-12-23 2003-12-23 Process for the production of 3'-nucleoside prodrugs Ceased WO2004058792A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
NZ540913A NZ540913A (en) 2002-12-23 2003-12-23 Process for the production of 3'-nucleoside prodrugs
MXPA05006865A MXPA05006865A (es) 2002-12-23 2003-12-23 Proceso para la produccion de profarmacos 3'-nucleosidos.
BR0316868-9A BR0316868A (pt) 2002-12-23 2003-12-23 Processo para a produção de pró-medicamentos de nucleosìdeo-3'
CA002511616A CA2511616A1 (en) 2002-12-23 2003-12-23 Process for the production of 3'-nucleoside prodrugs
JP2004562599A JP2006514038A (ja) 2002-12-23 2003-12-23 ３’−ヌクレオシドプロドラッグの生産方法
AU2003300434A AU2003300434A1 (en) 2002-12-23 2003-12-23 Process for the production of 3'-nucleoside prodrugs
EP03814400A EP1575971A4 (en) 2002-12-23 2003-12-23 PROCESS FOR THE PREPARATION OF 3-NUCLEOSIDE PRODRUGS
IL169314A IL169314A0 (en) 2002-12-23 2005-06-21 Process for the production of 3'-nucleoside prodrugs
NO20053557A NO20053557L (no) 2002-12-23 2005-07-20 Fremgangsmate for produksjon av 3'-nukleosid prolegemidler.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US43615002P 2002-12-23 2002-12-23
US60/436,150 2002-12-23

Publications (1)

Publication Number Publication Date
WO2004058792A1 true WO2004058792A1 (en) 2004-07-15

Family

ID=32682350

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2003/041603 Ceased WO2004058792A1 (en) 2002-12-23 2003-12-23 Process for the production of 3'-nucleoside prodrugs

Country Status (16)

Country Link
US (1) US20040181051A1 (https=)
EP (1) EP1575971A4 (https=)
JP (1) JP2006514038A (https=)
KR (1) KR20050110611A (https=)
CN (1) CN100335492C (https=)
AU (1) AU2003300434A1 (https=)
BR (1) BR0316868A (https=)
CA (1) CA2511616A1 (https=)
IL (1) IL169314A0 (https=)
MX (1) MXPA05006865A (https=)
NO (1) NO20053557L (https=)
NZ (1) NZ540913A (https=)
PL (1) PL377608A1 (https=)
RU (1) RU2005123395A (https=)
WO (1) WO2004058792A1 (https=)
ZA (1) ZA200505040B (https=)

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005123087A3 (en) * 2004-06-15 2006-07-13 Merck & Co Inc C-purine nucleoside analogs as inhibitors of rna-dependent rna viral polymerase
WO2007113159A1 (en) 2006-04-04 2007-10-11 F. Hoffmann-La Roche Ag 3',5'-di-o-acylated nucleosides for hcv treatment
WO2006050161A3 (en) * 2004-10-29 2007-12-21 Biocryst Pharm Inc Therapeutic furopyrimidines and thienopyrimidines
JP2008525459A (ja) * 2004-12-23 2008-07-17 ノバルティス アクチエンゲゼルシャフト Ｈｃｖ処置用組成物
US7456155B2 (en) 2002-06-28 2008-11-25 Idenix Pharmaceuticals, Inc. 2′-C-methyl-3′-O-L-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections
JP2008545619A (ja) * 2005-03-29 2008-12-18 バイオクライスト ファーマシューティカルズ， インコーポレイテッド Ｃ型肝炎治療
US7582618B2 (en) 2002-06-28 2009-09-01 Idenix Pharmaceuticals, Inc. 2′-C-methyl-3′-O-L-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections
US7598373B2 (en) 2002-12-12 2009-10-06 Idenix Pharmaceuticals, Inc. Process for the production of 2-C-methyl-D-ribonolactone
US7608597B2 (en) 2000-05-23 2009-10-27 Idenix Pharmaceuticals, Inc. Methods and compositions for treating hepatitis C virus
WO2010015637A1 (en) * 2008-08-06 2010-02-11 Novartis Ag New antiviral modified nucleosides
US8551973B2 (en) 2008-12-23 2013-10-08 Gilead Pharmasset Llc Nucleoside analogs
US8716262B2 (en) 2008-12-23 2014-05-06 Gilead Pharmasset Llc Nucleoside phosphoramidates
US8716263B2 (en) 2008-12-23 2014-05-06 Gilead Pharmasset Llc Synthesis of purine nucleosides
US8759318B2 (en) 2009-01-09 2014-06-24 Inhibitex, Inc. Phosphoramidate derivatives of guanosine nucleoside compounds for treatment of viral infections
US8802840B2 (en) 2005-03-08 2014-08-12 Biota Scientific Management Pty Ltd. Bicyclic nucleosides and nucleotides as therapeutic agents
US8859756B2 (en) 2010-03-31 2014-10-14 Gilead Pharmasset Llc Stereoselective synthesis of phosphorus containing actives
US9968628B2 (en) 2000-05-26 2018-05-15 Idenix Pharmaceuticals Llc Methods and compositions for treating flaviviruses and pestiviruses
US10525072B2 (en) 2002-11-15 2020-01-07 Idenix Pharmaceuticals Llc 2′-branched nucleosides and flaviviridae mutation
WO2020107013A1 (en) * 2018-11-25 2020-05-28 Bluevalley Pharmaceutical Llc Orally active prodrug of gemcitabine
US10946033B2 (en) 2016-09-07 2021-03-16 Atea Pharmaceuticals, Inc. 2′-substituted-N6-substituted purine nucleotides for RNA virus treatment

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7595390B2 (en) * 2003-04-28 2009-09-29 Novartis Ag Industrially scalable nucleoside synthesis
WO2007039413A2 (en) * 2005-09-22 2007-04-12 F. Hoffmann-La Roche Ag Selective o-acylation of nucleosides
WO2007095269A2 (en) * 2006-02-14 2007-08-23 Merck & Co., Inc. Nucleoside aryl phosphoramidates for the treatment of rna-dependent rna viral infection

Family Cites Families (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE29835E (en) * 1971-06-01 1978-11-14 Icn Pharmaceuticals 1,2,4-Triazole nucleosides
US3798209A (en) * 1971-06-01 1974-03-19 Icn Pharmaceuticals 1,2,4-triazole nucleosides
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
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.
US5223263A (en) * 1988-07-07 1993-06-29 Vical, Inc. Liponucleotide-containing liposomes
GB8719367D0 (en) * 1987-08-15 1987-09-23 Wellcome Found Therapeutic compounds
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
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
US5149794A (en) * 1990-11-01 1992-09-22 State Of Oregon Covalent lipid-drug conjugates for drug 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
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
US5157027A (en) * 1991-05-13 1992-10-20 E. R. Squibb & Sons, Inc. Bisphosphonate squalene synthetase inhibitors and method
US5554728A (en) * 1991-07-23 1996-09-10 Nexstar Pharmaceuticals, Inc. Lipid conjugates of therapeutic peptides and protease inhibitors
US5696277A (en) * 1994-11-15 1997-12-09 Karl Y. Hostetler Antiviral prodrugs
IL129126A0 (en) * 1996-10-16 2000-02-17 Icn Pharmaceuticals Monocyclic l-nucleosides analogs and uses thereof
US6248878B1 (en) * 1996-12-24 2001-06-19 Ribozyme Pharmaceuticals, Inc. Nucleoside analogs
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
US6172046B1 (en) * 1997-09-21 2001-01-09 Schering Corporation Combination therapy for eradicating detectable HCV-RNA in patients having chronic Hepatitis C infection
KR100719606B1 (ko) * 1998-02-25 2007-05-17 에모리 유니버시티 2'-플루오로뉴클레오사이드
US6312662B1 (en) * 1998-03-06 2001-11-06 Metabasis Therapeutics, Inc. Prodrugs phosphorus-containing compounds
CZ298681B6 (cs) * 1998-06-08 2007-12-19 F. Hoffmann-La Roche Ag Lécivo pro lécení infekcí chronické hepatitis C
WO2001018013A1 (en) * 1999-09-08 2001-03-15 Metabasis Therapeutics, Inc. Prodrugs for liver specific drug delivery
US6566365B1 (en) * 1999-11-04 2003-05-20 Biochem Pharma Inc. Method for the treatment of Flaviviridea viral infection using nucleoside analogues
CA2396713A1 (en) * 1999-12-22 2001-07-05 Metabasis Therapeutics, Inc. Novel bisamidate phosphonate prodrugs
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
EP1964569A3 (en) * 2000-04-13 2009-07-22 Pharmasset, Inc. 3'-or 2'-hydroxymethyl substituted nucleoside derivatives for treatment of viral infections
WO2001081359A1 (en) * 2000-04-20 2001-11-01 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
KR20080021797A (ko) * 2000-05-26 2008-03-07 이데닉스(케이만)리미티드 플라비바이러스 및 페스티바이러스의 치료방법 및 조성물
US6875751B2 (en) * 2000-06-15 2005-04-05 Idenix Pharmaceuticals, Inc. 3′-prodrugs of 2′-deoxy-β-L-nucleosides
US20030008841A1 (en) * 2000-08-30 2003-01-09 Rene Devos Anti-HCV nucleoside derivatives
EP1326594A2 (en) * 2000-10-18 2003-07-16 Schering Corporation Ribavirin-pegylated interferon alfa hcv combination therapy
KR20090089922A (ko) * 2000-10-18 2009-08-24 파마셋 인코포레이티드 바이러스 감염 및 비정상적인 세포 증식의 치료를 위한 변형된 뉴클레오시드
NZ575481A (en) * 2000-10-18 2010-10-29 Pharmasset Inc Simultaneous quantification of nucleic acids in diseased cells
US7105499B2 (en) * 2001-01-22 2006-09-12 Merck & Co., Inc. Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase
WO2002057425A2 (en) * 2001-01-22 2002-07-25 Merck & Co., Inc. Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase
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
WO2003024461A1 (en) * 2001-09-20 2003-03-27 Schering Corporation Hcv combination therapy
KR20040094692A (ko) * 2002-02-14 2004-11-10 파마셋, 리미티드 변형된 불소화 뉴클레오사이드 유사체
RU2004128943A (ru) * 2002-02-28 2005-04-20 Байота, Инк. (Us) Средства, имитирующие нуклеотиды, и их пролекарственные формы
US7247621B2 (en) * 2002-04-30 2007-07-24 Valeant Research & Development Antiviral phosphonate compounds and methods therefor
AU2003232071A1 (en) * 2002-05-06 2003-11-17 Genelabs Technologies, Inc. Nucleoside derivatives for treating hepatitis c virus infection
PL374781A1 (en) * 2002-06-28 2005-10-31 Idenix (Cayman) Limited 2'-c-methyl-3'-o-l-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections
MXPA04012779A (es) * 2002-06-28 2005-08-19 Idenix Cayman Ltd Profarmacos de 2'- y 3'-nucleosido para tratar infecciones por flaviviridae.
US7094768B2 (en) * 2002-09-30 2006-08-22 Genelabs Technologies, Inc. Nucleoside derivatives for treating hepatitis C virus infection
AU2003279797B2 (en) * 2002-09-30 2009-10-22 Genelabs Technologies, Inc. Nucleoside derivatives for treating hepatitis C virus infection
HUE033832T2 (en) * 2002-11-15 2018-01-29 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
RU2005121904A (ru) * 2002-12-12 2006-01-20 Айденикс (Кайман) Лимитед (Ky) Способ получения 2`-разветвленных нуклеозидов

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
MCCORMICK J ET AL: "Structure and total synthesis of hf-7, a neuroactive glyconucleoside disulfate from the funnel-web spider holoena curta", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 121, 1999, pages 5661 - 5665, XP002977718 *
See also references of EP1575971A4 *
TANG X Q ET AL: "2'-c-branched ribonucleosides: Synthesis of the phosphoramidite derivatives of 2'-c-beta-methylcytidine and their incorporation into oligonucleotides", JOURNAL OF ORGANIC CHEMISTRY, vol. 64, 1999, pages 747 - 754, XP002156891 *

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10758557B2 (en) 2000-05-23 2020-09-01 Idenix Pharmaceuticals Llc Methods and compositions for treating hepatitis C virus
US8299038B2 (en) 2000-05-23 2012-10-30 Idenix Pharmaceuticals, Inc. Methods and compositions for treating hepatitis C virus
US10363265B2 (en) 2000-05-23 2019-07-30 Idenix Pharmaceuticals Llc Methods and compositions for treating hepatitis C virus
US7608597B2 (en) 2000-05-23 2009-10-27 Idenix Pharmaceuticals, Inc. Methods and compositions for treating hepatitis C virus
US9968628B2 (en) 2000-05-26 2018-05-15 Idenix Pharmaceuticals Llc Methods and compositions for treating flaviviruses and pestiviruses
US7582618B2 (en) 2002-06-28 2009-09-01 Idenix Pharmaceuticals, Inc. 2′-C-methyl-3′-O-L-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections
US7456155B2 (en) 2002-06-28 2008-11-25 Idenix Pharmaceuticals, Inc. 2′-C-methyl-3′-O-L-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections
US10525072B2 (en) 2002-11-15 2020-01-07 Idenix Pharmaceuticals Llc 2′-branched nucleosides and flaviviridae mutation
US7598373B2 (en) 2002-12-12 2009-10-06 Idenix Pharmaceuticals, Inc. Process for the production of 2-C-methyl-D-ribonolactone
US7534767B2 (en) 2004-06-15 2009-05-19 Merck & Co., Inc. C-purine nucleoside analogs as inhibitors of RNA-dependent RNA viral polymerase
WO2005123087A3 (en) * 2004-06-15 2006-07-13 Merck & Co Inc C-purine nucleoside analogs as inhibitors of rna-dependent rna viral polymerase
JP2008502685A (ja) * 2004-06-15 2008-01-31 メルク　エンド　カムパニー　インコーポレーテッド 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
US7429571B2 (en) 2004-10-29 2008-09-30 Biocryst Pharmaceuticals, Inc. Therapeutic furopyrimidines and thienopyrimidines
US8133870B2 (en) 2004-10-29 2012-03-13 Biocryst Pharmaceuticals, Inc. Therapeutic furopyrimidines and thienopyrimidines
WO2006050161A3 (en) * 2004-10-29 2007-12-21 Biocryst Pharm Inc Therapeutic furopyrimidines and thienopyrimidines
JP2008525459A (ja) * 2004-12-23 2008-07-17 ノバルティス アクチエンゲゼルシャフト Ｈｃｖ処置用組成物
US8802840B2 (en) 2005-03-08 2014-08-12 Biota Scientific Management Pty Ltd. Bicyclic nucleosides and nucleotides as therapeutic agents
US8163703B2 (en) 2005-03-29 2012-04-24 Biocryst Pharmaceuticals, Inc. Hepatitis C therapies
JP2008545619A (ja) * 2005-03-29 2008-12-18 バイオクライスト ファーマシューティカルズ， インコーポレイテッド Ｃ型肝炎治療
WO2007113159A1 (en) 2006-04-04 2007-10-11 F. Hoffmann-La Roche Ag 3',5'-di-o-acylated nucleosides for hcv treatment
WO2010015637A1 (en) * 2008-08-06 2010-02-11 Novartis Ag New antiviral modified nucleosides
US8716262B2 (en) 2008-12-23 2014-05-06 Gilead Pharmasset Llc Nucleoside phosphoramidates
US8716263B2 (en) 2008-12-23 2014-05-06 Gilead Pharmasset Llc Synthesis of purine nucleosides
US8957045B2 (en) 2008-12-23 2015-02-17 Gilead Pharmasset Llc Nucleoside phosphoramidates
US9045520B2 (en) 2008-12-23 2015-06-02 Gilead Pharmasset Llc Synthesis of purine nucleosides
US8551973B2 (en) 2008-12-23 2013-10-08 Gilead Pharmasset Llc Nucleoside analogs
US8759318B2 (en) 2009-01-09 2014-06-24 Inhibitex, Inc. Phosphoramidate derivatives of guanosine nucleoside compounds for treatment of viral infections
US8859756B2 (en) 2010-03-31 2014-10-14 Gilead Pharmasset Llc Stereoselective synthesis of phosphorus containing actives
US10946033B2 (en) 2016-09-07 2021-03-16 Atea Pharmaceuticals, Inc. 2′-substituted-N6-substituted purine nucleotides for RNA virus treatment
US11975016B2 (en) 2016-09-07 2024-05-07 Atea Pharmaceuticals, Inc. 2′-substituted-N6-substituted purine nucleotides for RNA virus treatment
WO2020107013A1 (en) * 2018-11-25 2020-05-28 Bluevalley Pharmaceutical Llc Orally active prodrug of gemcitabine

Also Published As

Publication number Publication date
MXPA05006865A (es) 2005-12-12
KR20050110611A (ko) 2005-11-23
PL377608A1 (pl) 2006-02-06
CA2511616A1 (en) 2004-07-15
US20040181051A1 (en) 2004-09-16
IL169314A0 (en) 2007-07-04
EP1575971A4 (en) 2008-03-05
ZA200505040B (en) 2006-04-26
JP2006514038A (ja) 2006-04-27
AU2003300434A1 (en) 2004-07-22
CN100335492C (zh) 2007-09-05
RU2005123395A (ru) 2006-01-27
BR0316868A (pt) 2005-10-25
NZ540913A (en) 2008-02-29
NO20053557L (no) 2005-09-08
CN1751058A (zh) 2006-03-22
EP1575971A1 (en) 2005-09-21

Similar Documents

Publication Publication Date Title
US20040181051A1 (en) Process for the production of 3'-nucleoside prodrugs
EP2319853B1 (en) Process for the production of 2'-branched nucleosides
AU2009329872B2 (en) Synthesis of purine nucleosides
EP1773856B1 (en) Preparation of alkyl-substituted 2-deoxy-2-fluoro-d-ribofuranosyl pyrimidines and purines and their derivatives
US7582748B2 (en) Methods of manufacture of 2′-deoxy-β-L-nucleosides
CN101023094A (zh) 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
JP2008507547A6 (ja) アルキル置換された２−デオキシ−２−フルオロ−ｄ−リボフラノシルピリミジン類及びプリン類及びそれらの誘導体の調製
WO2013013009A2 (en) 2',3'-DIDEOXY-2'-α-FLUORO-2'-β-C-METHYLNUCLEOSIDES AND PRODRUGS THEREOF
WO2015095305A1 (en) Production of cyclic phosphate, phosphoramidate, thiophosphate, and phosphonate nucleoside compounds
US7595390B2 (en) Industrially scalable nucleoside synthesis
HK1160141A (en) Preparation of alkyl-substituted 2-deoxy-2-fluoro-d-ribofuranosyl pyrimidines and purines and their derivatives
HK1106249B (en) Preparation of alkyl-substituted 2-deoxy-2-fluoro-d-ribofuranosyl pyrimidines and purines and their derivatives

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 169314

Country of ref document: IL

Ref document number: 2005/05040

Country of ref document: ZA

Ref document number: 200505040

Country of ref document: ZA

WWE Wipo information: entry into national phase

Ref document number: PA/a/2005/006865

Country of ref document: MX

Ref document number: 1-2005-501202

Country of ref document: PH

Ref document number: 2004562599

Country of ref document: JP

Ref document number: 1020057011749

Country of ref document: KR

Ref document number: 2003300434

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 377608

Country of ref document: PL

Ref document number: 2511616

Country of ref document: CA

Ref document number: 540913

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 2003814400

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2005123395

Country of ref document: RU

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 20038A98204

Country of ref document: CN

WWP Wipo information: published in national office

Ref document number: 2003814400

Country of ref document: EP

ENP Entry into the national phase

Ref document number: PI0316868

Country of ref document: BR

WWP Wipo information: published in national office

Ref document number: 1020057011749

Country of ref document: KR