WO2002069903A3 - Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases - Google Patents

Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases Download PDF

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Publication number
WO2002069903A3
WO2002069903A3 PCT/US2002/006551 US0206551W WO02069903A3 WO 2002069903 A3 WO2002069903 A3 WO 2002069903A3 US 0206551 W US0206551 W US 0206551W WO 02069903 A3 WO02069903 A3 WO 02069903A3
Authority
WO
WIPO (PCT)
Prior art keywords
halosubstituted
substituted
nr1r2
aryl
alkyl
Prior art date
Application number
PCT/US2002/006551
Other languages
French (fr)
Other versions
WO2002069903A2 (en
Inventor
John A Montgomery
Yarlagadda S Babu
R Scott Rowland
Pooran Chand
Original Assignee
Biocryst Pharm Inc
John A Montgomery
Yarlagadda S Babu
R Scott Rowland
Pooran Chand
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
Application filed by Biocryst Pharm Inc, John A Montgomery, Yarlagadda S Babu, R Scott Rowland, Pooran Chand filed Critical Biocryst Pharm Inc
Priority to US10/471,056 priority Critical patent/US20040138170A1/en
Priority to AU2002252183A priority patent/AU2002252183A1/en
Publication of WO2002069903A2 publication Critical patent/WO2002069903A2/en
Publication of WO2002069903A3 publication Critical patent/WO2002069903A3/en

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Classifications

    • 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
    • A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • C07H19/10—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
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The compounds represented by the formulae (I) wherein X is selected from the group consisting of: O, S, N-R1, and CHR1; Y and Y' is individually selected from H, OR?1, NR1R2¿, and N¿3? Z and Z' is individually selected from H, OR?1¿, and NR1R2 R = H, formula (II), formula (III), or formula (III), R?1 and R2¿ is selected from H, alkyl, acyl, aryl which may be substituted or unsubstituted, R3 is selected from H, alkyl, alkenyl, alkynyl, aryl, acyloxyalkyl, and pivaloyloxyalkyl, B is selected from 5 or 6-substituted uracil or cytosine, pseudouracil, N-substituted pseudouracil, 2-thiouracil, 2-thiocytosine, 5- or 6-substituted 2-thiouracil and 2-thiocytosine, 6-azauracil, 5-azacytosine, 8-azapurines, and 7-aza-8-deazapurines. Substitutions may be halosubstituted alkyl, halosubstituted alkenyl, halosubstituted alkynyl, halosubstituted aryl, alkylthio, or NR1R2. When Z and Z' are H and Y or Y' is OH then B is not 5-methyl uracil or cytosine; and pharmaceutically acceptable salts thereof, mono, di or triphosphate and prodrugs thereof.
PCT/US2002/006551 2001-03-06 2002-03-06 Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases WO2002069903A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US10/471,056 US20040138170A1 (en) 2002-03-06 2002-03-06 Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases
AU2002252183A AU2002252183A1 (en) 2001-03-06 2002-03-06 Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US27334201P 2001-03-06 2001-03-06
US60/273,342 2001-03-06
US28569801P 2001-04-24 2001-04-24
US60/285,698 2001-04-24
US33132301P 2001-11-14 2001-11-14
US60/331,323 2001-11-14

Publications (2)

Publication Number Publication Date
WO2002069903A2 WO2002069903A2 (en) 2002-09-12
WO2002069903A3 true WO2002069903A3 (en) 2003-02-27

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/006551 WO2002069903A2 (en) 2001-03-06 2002-03-06 Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases

Country Status (2)

Country Link
AU (1) AU2002252183A1 (en)
WO (1) WO2002069903A2 (en)

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US8835449B2 (en) 2011-11-11 2014-09-16 Pfizer Inc. 2-thiopyrimidinones
US9394330B2 (en) 2012-03-21 2016-07-19 Alios Biopharma, Inc. Solid forms of a thiophosphoramidate nucleotide prodrug

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US7105499B2 (en) 2001-01-22 2006-09-12 Merck & Co., Inc. Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase
RS50236B (en) 2001-01-22 2009-07-15 Merck & Co.Inc., Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase
US8481712B2 (en) 2001-01-22 2013-07-09 Merck Sharp & Dohme Corp. Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase
US6905669B2 (en) 2001-04-24 2005-06-14 Supergen, Inc. Compositions and methods for reestablishing gene transcription through inhibition of DNA methylation and histone deacetylase
US6998391B2 (en) 2002-02-07 2006-02-14 Supergen.Inc. Method for treating diseases associated with abnormal kinase activity
US6982253B2 (en) 2002-06-05 2006-01-03 Supergen, Inc. Liquid formulation of decitabine and use of the same
US20050075279A1 (en) 2002-10-25 2005-04-07 Boehringer Ingelheim International Gmbh Macrocyclic peptides active against the hepatitis C virus
US7223785B2 (en) 2003-01-22 2007-05-29 Boehringer Ingelheim International Gmbh Viral polymerase inhibitors
RS20060259A (en) 2003-10-14 2008-08-07 Intermune Inc., Macrocyclic carboxylic acids and acylsulfonamides as inhibitors of hcv replication
ES2358333T3 (en) 2004-01-21 2011-05-09 Boehringer Ingelheim International Gmbh MACROCYCLIC PEPTIDES WITH ACTION AGAINST THE VIRUS OF HEPATITIS C.
EP1718608B1 (en) 2004-02-20 2013-07-17 Boehringer Ingelheim International GmbH Viral polymerase inhibitors
US7250416B2 (en) 2005-03-11 2007-07-31 Supergen, Inc. Azacytosine analogs and derivatives
EA016071B1 (en) 2005-05-13 2012-01-30 Вирокем Фарма Инк. Compounds and methods for the treatment or prevention of flavivirus infections
US7700567B2 (en) 2005-09-29 2010-04-20 Supergen, Inc. Oligonucleotide analogues incorporating 5-aza-cytosine therein
US8067391B2 (en) 2005-10-03 2011-11-29 University Health Network ODCase inhibitors for the treatment of malaria
RS52874B (en) 2006-11-15 2013-12-31 Vertex Pharmaceuticals Incorporated Thiophene analogues for the treatment or prevention of flavivirus infections
EP2341924A4 (en) 2008-10-02 2013-01-23 David Gladstone Inst Methods of treating hepatitis c virus infection
US8975247B2 (en) 2009-03-18 2015-03-10 The Board Of Trustees Of The Leland Stanford Junion University Methods and compositions of treating a flaviviridae family viral infection
CA2781614A1 (en) 2009-11-25 2011-06-09 Vertex Pharmaceuticals Incorporated 5-alkynyl-thiophene-2-carboxylic acid derivatives and their use for the treatment or prevention of flavivirus infections
AU2010336355A1 (en) 2009-12-24 2012-07-05 Vertex Pharmaceuticals Incorporated Analogues for the treatment or prevention of flavivirus infections
TW201141857A (en) 2010-03-24 2011-12-01 Vertex Pharma Analogues for the treatment or prevention of flavivirus infections
TW201139438A (en) 2010-03-24 2011-11-16 Vertex Pharma Analogues for the treatment or prevention of flavivirus infections
WO2011119870A1 (en) 2010-03-24 2011-09-29 Vertex Pharmaceuticals Incorporated Analogues for the treatment or prevention of flavivirus infections
WO2011119853A1 (en) 2010-03-24 2011-09-29 Vertex Pharmaceuticals Incorporated Analogues for the treatment or prevention of flavivirus infections
US20130157258A1 (en) 2010-06-15 2013-06-20 Vertex Pharmaceuticals Incorporated Hcv ns5b protease mutants
EP2585448A1 (en) 2010-06-28 2013-05-01 Vertex Pharmaceuticals Incorporated Compounds and methods for the treatment or prevention of flavivirus infections
WO2012006070A1 (en) 2010-06-28 2012-01-12 Vertex Pharmaceuticals Incorporated Compounds and methods for the treatment or prevention of flavivirus infections
UY33473A (en) 2010-06-28 2012-01-31 Vertex Pharma COMPOUNDS AND METHODS FOR THE TREATMENT OR PREVENTION OF FLAVIVIRUS INFECTIONS
CA2808291A1 (en) 2010-08-17 2012-02-23 Vertex Pharmaceuticals Incorporated Compounds and methods for the treatment or prevention of flaviviridae viral infections
NZ607996A (en) 2010-09-22 2014-07-25 Alios Biopharma Inc Substituted nucleotide analogs
EP2697242B1 (en) 2011-04-13 2018-10-03 Merck Sharp & Dohme Corp. 2'-azido substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases
JP2014515023A (en) 2011-04-13 2014-06-26 メルク・シャープ・アンド・ドーム・コーポレーション 2'-substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases
AU2012242978A1 (en) 2011-04-13 2013-10-24 Merck Sharp & Dohme Corp. 2'-Cyano Substituted Nucleoside Derivatives and methods of use thereof for the treatment of viral diseases
US9408863B2 (en) 2011-07-13 2016-08-09 Merck Sharp & Dohme Corp. 5′-substituted nucleoside analogs and methods of use thereof for the treatment of viral diseases
US9416154B2 (en) 2011-07-13 2016-08-16 Merck Sharp & Dohme Corp. 5′-substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases
WO2013016499A1 (en) 2011-07-26 2013-01-31 Vertex Pharmaceuticals Incorporated Methods for preparation of thiophene compounds
AR087344A1 (en) 2011-07-26 2014-03-19 Vertex Pharma ACID POLYMORPHIC FORMS 5- (3,3-DIMETIL-BUT-1-INIL) -3 - [(TRANS-4-HIDROXI-CICLOHEXIL) - (TRANS-4-METHYL-CYCLHEXANCARBONYL) -AMINO] -TIOFEN-2- CARBOXILICO AND ITS USE IN THE TREATMENT OF HEPATITIS C
AU2012302051B2 (en) 2011-08-30 2017-04-27 Astex Pharmaceuticals, Inc. Decitabine derivative formulations
BR112014013649A2 (en) 2011-12-06 2020-10-27 The Board Of Trustees Of The Leland Stanford Junior University methods and agents for the treatment of viral diseases and uses of said agents
EP2794630A4 (en) 2011-12-22 2015-04-01 Alios Biopharma Inc Substituted phosphorothioate nucleotide analogs
WO2013142157A1 (en) 2012-03-22 2013-09-26 Alios Biopharma, Inc. Pharmaceutical combinations comprising a thionucleotide analog
AR090699A1 (en) 2012-04-18 2014-12-03 Biocryst Pharm Inc INHIBITING COMPOUNDS OF VIRAL POLYMERASE RNA ACTIVITY
WO2014134251A1 (en) 2013-02-28 2014-09-04 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions
MX2016017381A (en) 2014-06-24 2017-08-14 Alios Biopharma Inc Substituted nucleosides, nucleotides and analogs thereof.
MX2017014128A (en) 2015-05-05 2018-03-15 Pfizer 2-thiopyrimidinones.
EP3316685A4 (en) 2015-07-02 2019-03-13 Otsuka Pharmaceutical Co., Ltd. Lyophilized pharmaceutical compositions
WO2019025863A2 (en) 2017-08-03 2019-02-07 Otsuka Pharmaceutical Co., Ltd. Drug compound and purification methods thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5726174A (en) * 1989-05-15 1998-03-10 Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic Nucleoside analogs
US6063628A (en) * 1996-10-28 2000-05-16 University Of Washington Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA
US6348587B1 (en) * 1998-02-25 2002-02-19 Emory University 2′-Fluoronucleosides

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5726174A (en) * 1989-05-15 1998-03-10 Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic Nucleoside analogs
US6063628A (en) * 1996-10-28 2000-05-16 University Of Washington Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA
US6348587B1 (en) * 1998-02-25 2002-02-19 Emory University 2′-Fluoronucleosides

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8835449B2 (en) 2011-11-11 2014-09-16 Pfizer Inc. 2-thiopyrimidinones
US8841314B2 (en) 2011-11-11 2014-09-23 Pfizer Inc. 2-Thiopyrimidinones
US9399626B2 (en) 2011-11-11 2016-07-26 Pfizer Inc. 2-thiopyrimidinones
US9394330B2 (en) 2012-03-21 2016-07-19 Alios Biopharma, Inc. Solid forms of a thiophosphoramidate nucleotide prodrug

Also Published As

Publication number Publication date
AU2002252183A1 (en) 2002-09-19
WO2002069903A2 (en) 2002-09-12

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