WO2008104408A3 - Phosphate modified nucleosides useful as substrates for polymerases and as antiviral agents - Google Patents

Phosphate modified nucleosides useful as substrates for polymerases and as antiviral agents Download PDF

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Publication number
WO2008104408A3
WO2008104408A3 PCT/EP2008/001764 EP2008001764W WO2008104408A3 WO 2008104408 A3 WO2008104408 A3 WO 2008104408A3 EP 2008001764 W EP2008001764 W EP 2008001764W WO 2008104408 A3 WO2008104408 A3 WO 2008104408A3
Authority
WO
WIPO (PCT)
Prior art keywords
substrates
group
modified nucleosides
polymerases
amino
Prior art date
Application number
PCT/EP2008/001764
Other languages
French (fr)
Other versions
WO2008104408A2 (en
Inventor
Olga Adelfinskaya
Piet Herdewijn
Original Assignee
Leuven K U Res & Dev
Olga Adelfinskaya
Piet Herdewijn
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 claimed from GB0703722A external-priority patent/GB0703722D0/en
Priority claimed from GB0703715A external-priority patent/GB0703715D0/en
Priority claimed from GB0718229A external-priority patent/GB0718229D0/en
Priority claimed from GB0718228A external-priority patent/GB0718228D0/en
Application filed by Leuven K U Res & Dev, Olga Adelfinskaya, Piet Herdewijn filed Critical Leuven K U Res & Dev
Priority to EP08716281A priority Critical patent/EP2144921A2/en
Publication of WO2008104408A2 publication Critical patent/WO2008104408A2/en
Publication of WO2008104408A3 publication Critical patent/WO2008104408A3/en
Priority to US12/549,117 priority patent/US8242087B2/en
Priority to US13/266,954 priority patent/US20120108533A1/en

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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
    • 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
    • C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • 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
    • C07H19/16—Purine radicals
    • C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)

Abstract

This invention provides phosphate-modified nucleosides represented by the structural formula: wherein - B is a pyrimidine or purine base, or an analogue thereof, optionally substituted with one or two substituents independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, methyl, ethyl, amino and methylamino; - R1 is H or OH; - R3 is selected from the group consisting of H, C1-6 alkyl, C3-6 cycloalkyl, aryl-C1-6alkyl and 2-cyanoethyl, wherein said C1-6 alkyl, C3-6 cycloalkyl or aryl-C1-6 alkyl is optionally substituted with one or more, preferably 1, 2 or 3, substituents independently selected from the group consisting of halogen, OH, C1-6 alkoxy, trifluoromethyl, trifluoromethoxy, nitro, cyano and amino; - W is O or S; and - R2 is a group derived from an amino-acid. These compounds are useful as substrates for DNA/RNA polymerases, and as anti-viral agents.
PCT/EP2008/001764 2007-02-27 2008-02-27 Phosphate modified nucleosides useful as substrates for polymerases and as antiviral agents WO2008104408A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP08716281A EP2144921A2 (en) 2007-02-27 2008-02-27 Phosphate modified nucleosides useful as substrates for polymerases and as antiviral agents
US12/549,117 US8242087B2 (en) 2007-02-27 2009-08-27 Phosphate modified nucleosides useful as substrates for polymerases and as antiviral agents
US13/266,954 US20120108533A1 (en) 2007-02-27 2010-04-30 Novel phosphate modified nucleosides useful as substrates for polymerases and as antiviral agents

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
GB0703722A GB0703722D0 (en) 2007-02-27 2007-02-27 Novel modified nucleotides as substrate for polymerases
GB0703715.3 2007-02-27
GB0703722.9 2007-02-27
GB0703715A GB0703715D0 (en) 2007-02-27 2007-02-27 Novel modified nucleotides with antiviral activity
GB0718229.8 2007-09-17
GB0718229A GB0718229D0 (en) 2007-09-17 2007-09-17 New modified nucleotides with antiviral activity
GB0718228.0 2007-09-17
GB0718228A GB0718228D0 (en) 2007-09-17 2007-09-17 New modified nucleotides as substrate for polymerases

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/549,117 Continuation-In-Part US8242087B2 (en) 2007-02-27 2009-08-27 Phosphate modified nucleosides useful as substrates for polymerases and as antiviral agents

Publications (2)

Publication Number Publication Date
WO2008104408A2 WO2008104408A2 (en) 2008-09-04
WO2008104408A3 true WO2008104408A3 (en) 2008-12-04

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2008/001764 WO2008104408A2 (en) 2007-02-27 2008-02-27 Phosphate modified nucleosides useful as substrates for polymerases and as antiviral agents

Country Status (2)

Country Link
EP (1) EP2144921A2 (en)
WO (1) WO2008104408A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9394330B2 (en) 2012-03-21 2016-07-19 Alios Biopharma, Inc. Solid forms of a thiophosphoramidate nucleotide prodrug

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GB0623493D0 (en) 2006-11-24 2007-01-03 Univ Cardiff Chemical compounds
WO2010125200A1 (en) * 2009-04-30 2010-11-04 Katholieke Universiteit Leuven, K.U. Leuven R&D Novel phosphate modified nucleosides useful as substrates for polymerases and as antiviral angents
US8242087B2 (en) 2007-02-27 2012-08-14 K.U.Leuven Research & Development Phosphate modified nucleosides useful as substrates for polymerases and as antiviral agents
US7964580B2 (en) 2007-03-30 2011-06-21 Pharmasset, Inc. Nucleoside phosphoramidate prodrugs
US8404830B2 (en) 2007-07-17 2013-03-26 Somalogic, Inc. Method for generating aptamers with improved off-rates
GB0921443D0 (en) * 2009-12-08 2010-01-20 Univ Leuven Kath Novel phosph(on)ate-and sulf(on)ate-based phosphate modified nucleosides useful as substrates for polymerases and as antiviral agents
CA3066785A1 (en) 2010-04-12 2011-10-20 Somalogic, Inc. 5-position modified pyrimidines and their use
SG188497A1 (en) 2010-09-22 2013-05-31 Alios Biopharma Inc Substituted nucleotide analogs
CA2860234A1 (en) 2011-12-22 2013-06-27 Alios Biopharma, Inc. Substituted phosphorothioate nucleotide analogs
WO2013142157A1 (en) 2012-03-22 2013-09-26 Alios Biopharma, Inc. Pharmaceutical combinations comprising a thionucleotide analog
CN107312039B (en) 2012-08-30 2019-06-25 江苏豪森药业集团有限公司 A kind of preparation method of tenofovir prodrug
US9534243B2 (en) 2013-02-07 2017-01-03 The United States Of America, As Represented By The Secretary Of Commerce Nucleotide analogs and process for making same enzyme
SG10201800188SA (en) 2013-03-15 2018-02-27 Univ California Acyclic nucleoside phosphonate diesters
PT3650014T (en) 2013-08-27 2021-12-27 Gilead Pharmasset Llc Combination formulation of two antiviral compounds
AU2014353102B2 (en) 2013-11-21 2019-05-16 Somalogic Operating Co., Inc. Cytidine-5-carboxamide modified nucleotide compositions and methods related thereto
CN103804446A (en) * 2014-02-27 2014-05-21 苏州东南药业股份有限公司 Preparation method of 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribo-gamma-lactone
JP6708329B2 (en) 2014-09-15 2020-06-10 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Nucleotide analogues
WO2017048956A1 (en) * 2015-09-15 2017-03-23 The Regents Of The University Of California Nucleotide analogs
WO2022008025A1 (en) * 2020-07-05 2022-01-13 Since & Technology Development Fund Authority 2-hydroxyiminopyrimidine nucleosides and derivitives and antiviral uses thereto
CN112521436B (en) * 2020-12-08 2022-09-16 吉林百年汉克制药有限公司 Preparation method of 5' -cytidylic acid derivative and application of derivative in citicoline, citicoline sodium and injection thereof

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Patent Citations (5)

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WO2006012078A2 (en) * 2004-06-24 2006-02-02 Merck & Co., Inc. Nucleoside aryl phosphoramidates for the treatment of rna-dependent rna viral infection
WO2006063149A1 (en) * 2004-12-09 2006-06-15 Regents Of The University Of Minnesota Nucleosides with antiviral and anticancer activity
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9394330B2 (en) 2012-03-21 2016-07-19 Alios Biopharma, Inc. Solid forms of a thiophosphoramidate nucleotide prodrug

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WO2008104408A2 (en) 2008-09-04
EP2144921A2 (en) 2010-01-20

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