DE69729877T2 - Mycophenol bisphosponatverbindungen - Google Patents

Mycophenol bisphosponatverbindungen Download PDF

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Publication number
DE69729877T2
DE69729877T2 DE69729877T DE69729877T DE69729877T2 DE 69729877 T2 DE69729877 T2 DE 69729877T2 DE 69729877 T DE69729877 T DE 69729877T DE 69729877 T DE69729877 T DE 69729877T DE 69729877 T2 DE69729877 T2 DE 69729877T2
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Prior art keywords
phosphonate
hydroxy
methoxy
methyl
phthalan
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Expired - Lifetime
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DE69729877T
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German (de)
English (en)
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DE69729877D1 (de
Inventor
W. Krzysztof PANKIEWICZ
Krystyna Lesiak
A. Kyoichi WATANABE
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Pharmasset Ltd
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Pharmasset Ltd
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Publication of DE69729877D1 publication Critical patent/DE69729877D1/de
Publication of DE69729877T2 publication Critical patent/DE69729877T2/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06Pyrimidine radicals
    • C07H19/10Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/28Phosphorus compounds with one or more P—C bonds
    • C07F9/30Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/32Esters thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/06Phosphorus compounds without P—C bonds
    • C07F9/22Amides of acids of phosphorus
    • C07F9/24Esteramides
    • C07F9/2454Esteramides the amide moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/2479Compounds containing the structure P(=X)n-N-acyl, P(=X)n-N-heteroatom, P(=X)n-N-CN (X = O, S, Se; n = 0, 1)
    • C07F9/2495Compounds containing the structure P(=X)n-N-acyl, P(=X)n-N-heteroatom, P(=X)n-N-CN (X = O, S, Se; n = 0, 1) containing the structure P(=X)n-N-P (X = O, S, Se; n = 0, 1)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/28Phosphorus compounds with one or more P—C bonds
    • C07F9/30Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/32Esters thereof
    • C07F9/3205Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/3235Esters of poly(thio)phosphinic acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/28Phosphorus compounds with one or more P—C bonds
    • C07F9/38Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40Esters thereof
    • C07F9/4003Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4025Esters of poly(thio)phosphonic acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/28Phosphorus compounds with one or more P—C bonds
    • C07F9/38Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/44Amides thereof
    • C07F9/4403Amides thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4423Amides of poly (thio)phosphonic acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6571Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/657163Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom
    • C07F9/657172Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and one oxygen atom being part of a (thio)phosphinic acid ester: (X = O, S)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6571Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/657163Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom
    • C07F9/657181Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and, at least, one ring oxygen atom being part of a (thio)phosphonic acid derivative
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16Purine radicals
    • C07H19/20Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16Purine radicals
    • C07H19/20Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • C07H19/207Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
DE69729877T 1996-10-09 1997-10-09 Mycophenol bisphosponatverbindungen Expired - Lifetime DE69729877T2 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US2815496P 1996-10-09 1996-10-09
US28154P 1996-10-09
US3836097P 1997-02-13 1997-02-13
US38360P 1997-02-13
PCT/US1997/018323 WO1998015563A1 (en) 1996-10-09 1997-10-09 Tetraphosphonate bicyclic trisanhydrides

Publications (2)

Publication Number Publication Date
DE69729877D1 DE69729877D1 (de) 2004-08-19
DE69729877T2 true DE69729877T2 (de) 2005-07-14

Family

ID=26703363

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69729877T Expired - Lifetime DE69729877T2 (de) 1996-10-09 1997-10-09 Mycophenol bisphosponatverbindungen

Country Status (13)

Country Link
US (2) US6326490B1 (enExample)
EP (1) EP0934325B1 (enExample)
JP (1) JP4118958B2 (enExample)
KR (1) KR100560182B1 (enExample)
CN (1) CN1113888C (enExample)
AT (1) ATE271058T1 (enExample)
AU (1) AU4815197A (enExample)
BR (1) BR9712285A (enExample)
CA (1) CA2268434C (enExample)
DE (1) DE69729877T2 (enExample)
ES (1) ES2225958T3 (enExample)
PT (1) PT934325E (enExample)
WO (1) WO1998015563A1 (enExample)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
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AU4815197A (en) 1996-10-09 1998-05-05 Pharmasset, Ltd. Tetraphosphonate bicyclic trisanhydrides
WO1998034942A2 (en) * 1997-02-06 1998-08-13 Inspire Pharmaceuticals, Inc. Dinucleotides and their use
US7223744B2 (en) 1997-02-10 2007-05-29 Inspire Pharmaceuticals, Inc. Pharmaceutical formulation comprising dinucleoside polyphosphates and salts thereof
US20040181078A1 (en) * 1997-10-10 2004-09-16 Pharmasset, Ltd. Tetraphosphonate bicyclic trisanhydrides
CA2394654A1 (en) 1999-12-17 2001-06-21 Manfred Weigele Proton pump inhibitors
IL150060A0 (en) * 1999-12-17 2002-12-01 Ariad Pharma Inc Novel purines
US6787526B1 (en) 2000-05-26 2004-09-07 Idenix Pharmaceuticals, Inc. Methods of treating hepatitis delta virus infection with β-L-2′-deoxy-nucleosides
US6875751B2 (en) 2000-06-15 2005-04-05 Idenix Pharmaceuticals, Inc. 3′-prodrugs of 2′-deoxy-β-L-nucleosides
US6867199B2 (en) 2000-08-21 2005-03-15 Inspire Pharmaceuticals, Inc. Dinucleoside polyphosphate compositions and their therapeutic use
US6555675B2 (en) 2000-08-21 2003-04-29 Inspire Pharmaceuticals, Inc. Dinucleoside polyphosphate compositions and their therapuetic use as purinergic receptor agonists
BR0116221A (pt) * 2000-12-15 2005-09-13 Pharmasset Ltd Agentes antivirais para tratamento de infecções por flaviviridae
WO2004096287A2 (en) 2003-04-25 2004-11-11 Gilead Sciences, Inc. Inosine monophosphate dehydrogenase inhibitory phosphonate compounds
US7452901B2 (en) 2003-04-25 2008-11-18 Gilead Sciences, Inc. Anti-cancer phosphonate analogs
WO2004096285A2 (en) 2003-04-25 2004-11-11 Gilead Sciences, Inc. Anti-infective phosphonate conjugates
US7432261B2 (en) 2003-04-25 2008-10-07 Gilead Sciences, Inc. Anti-inflammatory phosphonate compounds
PT1628685E (pt) 2003-04-25 2011-03-16 Gilead Sciences Inc Análogos de fosfonatos antivirais
WO2005002626A2 (en) 2003-04-25 2005-01-13 Gilead Sciences, Inc. Therapeutic phosphonate compounds
US7470724B2 (en) 2003-04-25 2008-12-30 Gilead Sciences, Inc. Phosphonate compounds having immuno-modulatory activity
JP2006524710A (ja) 2003-04-25 2006-11-02 ギリアード サイエンシーズ, インコーポレイテッド キナーゼインヒビターホスホネート抱合体
US7407965B2 (en) 2003-04-25 2008-08-05 Gilead Sciences, Inc. Phosphonate analogs for treating metabolic diseases
ES2586668T5 (es) 2003-05-30 2024-11-12 Gilead Pharmasset Llc Análogos de nucleósidos fluorados modificados
WO2005044279A1 (en) 2003-10-24 2005-05-19 Gilead Sciences, Inc. Purine nucleoside phosphonate conjugates
US7432273B2 (en) 2003-10-24 2008-10-07 Gilead Sciences, Inc. Phosphonate analogs of antimetabolites
NZ547907A (en) 2003-12-22 2010-07-30 Gilead Sciences Inc 4'-Substituted carbovir-and abacavir-derivatives as well as related compounds with HIV and HCV antiviral activity
DE10361932A1 (de) * 2003-12-30 2005-07-28 Celanese Ventures Gmbh Protonenleitende Membran und deren Verwendung
DE10361832A1 (de) * 2003-12-30 2005-07-28 Celanese Ventures Gmbh Protonenleitende Membran und deren Verwendung
BRPI0512690A (pt) 2004-07-27 2007-11-27 Gilead Sciences Inc análogos de fosfonato de compostos inibidores de hiv
EA200801028A1 (ru) * 2005-10-06 2008-10-30 Иннейт Фарма Соли фосфоантигенов с органическими основаниями и способы их кристаллизации
US20090111774A1 (en) * 2007-06-01 2009-04-30 Luitpold Pharmaceuticals, Inc. Pmea lipid conjugates
EP2303285A2 (en) * 2008-02-15 2011-04-06 MicroDose Therapeutx, Inc. Methods of making nucleoside tetraphosphate analogs
PT2307435E (pt) 2008-07-08 2012-09-19 Gilead Sciences Inc Sais de compostos inibidores de vih
WO2010048585A2 (en) 2008-10-24 2010-04-29 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
EP3091027B1 (en) 2010-04-28 2018-01-17 Ionis Pharmaceuticals, Inc. 5' modified nucleosides and oligomeric compounds prepared therefrom
EP2606057B1 (en) 2010-04-28 2016-06-15 Ionis Pharmaceuticals, Inc. Modified 5' diphosphate nucleosides and oligomeric compounds prepared therefrom
WO2011139702A2 (en) 2010-04-28 2011-11-10 Isis Pharmaceuticals, Inc. Modified nucleosides and oligomeric compounds prepared therefrom
CN105073768A (zh) * 2013-03-13 2015-11-18 达纳-法伯癌症研究所股份有限公司 Ras抑制剂及其用途
FI3399984T3 (fi) * 2016-01-08 2023-11-10 Arcus Biosciences Inc Ekto-5'-nukleotidaasin modulaattoreita ja niiden käyttö
EP3541396A4 (en) * 2016-11-18 2020-07-22 Arcus Biosciences, Inc. CD73-MEDIATED IMMUNOSUPPRESSION INHIBITORS
PT3661937T (pt) 2017-08-01 2021-09-24 Gilead Sciences Inc Formas cristalinas de ((s)-((((2r,5r)-5-(6-amino-9h-purin-9-il)-4-fluoro-2,5-dihidrofurano-2-il)oxi)metil)(fenoxi)fosforil)-l-alaninato de etil (gs-9131) para tratamento de infeções virais
WO2020210970A1 (en) * 2019-04-16 2020-10-22 Bioardis Llc Imidazotriazine derivatives as cd73 inhibitors
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Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FI89365C (fi) * 1990-12-20 1993-09-27 Leiras Oy Foerfarande foer framstaellning av nya farmakologiskt anvaendbara metylenbisfosfonsyraderivat
US5569650A (en) * 1993-06-11 1996-10-29 Sloan-Kettering Institute For Cancer Research C-nucleoside isosters of analogs thereof and pharmaceutical compositions
DE4341161A1 (de) * 1993-12-02 1995-06-08 Michael Prof Dr Zeppezauer Membrangängiger Wirkstoff zur Störung der DNA-Biosynthese
FR2721931B1 (fr) * 1994-06-30 1996-08-02 Commissariat Energie Atomique Conjugues d'analogues de diphosphates ou triphosphates avec des enzymes ou des proteurs antigeniques et dosage immunologique utilisant de tels conjugues
AU4815197A (en) 1996-10-09 1998-05-05 Pharmasset, Ltd. Tetraphosphonate bicyclic trisanhydrides

Also Published As

Publication number Publication date
CA2268434C (en) 2007-05-01
JP4118958B2 (ja) 2008-07-16
CA2268434A1 (en) 1998-04-16
AU4815197A (en) 1998-05-05
CN1113888C (zh) 2003-07-09
KR20000049026A (ko) 2000-07-25
US6326490B1 (en) 2001-12-04
KR100560182B1 (ko) 2006-03-13
CN1239964A (zh) 1999-12-29
ATE271058T1 (de) 2004-07-15
EP0934325B1 (en) 2004-07-14
JP2001501952A (ja) 2001-02-13
EP0934325A4 (en) 2000-08-16
PT934325E (pt) 2004-10-29
US20020161220A1 (en) 2002-10-31
EP0934325A1 (en) 1999-08-11
WO1998015563A1 (en) 1998-04-16
DE69729877D1 (de) 2004-08-19
ES2225958T3 (es) 2005-03-16
US6713623B2 (en) 2004-03-30
BR9712285A (pt) 2001-11-20

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