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 CA002511616A priority patent/CA2511616A1/en
Priority to EP03814400A priority patent/EP1575971A4/en
Priority to MXPA05006865A priority patent/MXPA05006865A/es
Priority to BR0316868-9A priority patent/BR0316868A/pt
Priority to NZ540913A priority patent/NZ540913A/en
Application filed by Idenix Cayman Ltd filed Critical Idenix Cayman Ltd
Priority to JP2004562599A priority patent/JP2006514038A/ja
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)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (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
CA002511616A CA2511616A1 (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
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'
NZ540913A NZ540913A (en) 2002-12-23 2003-12-23 Process for the production of 3'-nucleoside prodrugs
AU2003300434A AU2003300434A1 (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
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 (enExample)
EP (1) EP1575971A4 (enExample)
JP (1) JP2006514038A (enExample)
KR (1) KR20050110611A (enExample)
CN (1) CN100335492C (enExample)
AU (1) AU2003300434A1 (enExample)
BR (1) BR0316868A (enExample)
CA (1) CA2511616A1 (enExample)
IL (1) IL169314A0 (enExample)
MX (1) MXPA05006865A (enExample)
NO (1) NO20053557L (enExample)
NZ (1) NZ540913A (enExample)
PL (1) PL377608A1 (enExample)
RU (1) RU2005123395A (enExample)
WO (1) WO2004058792A1 (enExample)
ZA (1) ZA200505040B (enExample)

Cited By (20)

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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
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US10946033B2 (en) 2016-09-07 2021-03-16 Atea Pharmaceuticals, Inc. 2′-substituted-N6-substituted purine nucleotides for RNA virus treatment

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

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