CN1113888C - 四膦酸酯二环三酸酐 - Google Patents

四膦酸酯二环三酸酐 Download PDF

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Publication number
CN1113888C
CN1113888C CN97180340A CN97180340A CN1113888C CN 1113888 C CN1113888 C CN 1113888C CN 97180340 A CN97180340 A CN 97180340A CN 97180340 A CN97180340 A CN 97180340A CN 1113888 C CN1113888 C CN 1113888C
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CN
China
Prior art keywords
methyl
methoxy
hydroxy
lacton
fluoro
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Expired - Fee Related
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CN97180340A
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English (en)
Chinese (zh)
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CN1239964A (zh
Inventor
K·W·潘基维茨
K·勒斯尔克
K·A·瓦塔纳贝
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Pharmasset Ltd
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Pharmasset Ltd
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    • 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
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/32—Esters thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/22—Amides of acids of phosphorus
    • C07F9/24—Esteramides
    • C07F9/2454—Esteramides the amide moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/2479—Compounds 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)
    • C07F9/2495—Compounds 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)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/32—Esters thereof
    • C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/3235—Esters of poly(thio)phosphinic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4025—Esters of poly(thio)phosphonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/44—Amides thereof
    • C07F9/4403—Amides thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4423—Amides of poly (thio)phosphonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic 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
    • C07F9/6571—Heterocyclic 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
    • C07F9/657163—Heterocyclic 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
    • C07F9/657172—Heterocyclic 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)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic 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
    • C07F9/6571—Heterocyclic 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
    • C07F9/657163—Heterocyclic 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
    • C07F9/657181—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic 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
    • C07F9/6581—Heterocyclic 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
    • 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
    • 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
    • C07H19/207—Purine 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)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (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)
CN97180340A 1996-10-09 1997-10-09 四膦酸酯二环三酸酐 Expired - Fee Related CN1113888C (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US2815496P 1996-10-09 1996-10-09
US60/028,154 1996-10-09
US3836097P 1997-02-13 1997-02-13
US60/038,360 1997-02-13

Publications (2)

Publication Number Publication Date
CN1239964A CN1239964A (zh) 1999-12-29
CN1113888C true CN1113888C (zh) 2003-07-09

Family

ID=26703363

Family Applications (1)

Application Number Title Priority Date Filing Date
CN97180340A Expired - Fee Related CN1113888C (zh) 1996-10-09 1997-10-09 四膦酸酯二环三酸酐

Country Status (13)

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

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* Cited by examiner, † Cited by third party
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BR9712285A (pt) 1996-10-09 2001-11-20 Pharmasset Ltd Tetrafosfonato bicìclico de trianidridas
CN1262556C (zh) 1997-02-06 2006-07-05 印斯拜尔药品股份有限公司 特定的二核苷酸和它们作为粘膜纤毛清除和纤毛颤动频率调节剂的应用
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
JP2003531111A (ja) 1999-12-17 2003-10-21 アライアッド・ファーマシューティカルズ・インコーポレーテッド プロトンポンプインヒビター
ATE327242T1 (de) * 1999-12-17 2006-06-15 Ariad Pharma Inc Neue purine
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
WO2002048165A2 (en) * 2000-12-15 2002-06-20 Pharmasset Ltd. Antiviral agents for treatment of flaviviridae infections
US7470724B2 (en) 2003-04-25 2008-12-30 Gilead Sciences, Inc. Phosphonate compounds having immuno-modulatory activity
US7300924B2 (en) 2003-04-25 2007-11-27 Gilead Sciences, Inc. Anti-infective phosphonate analogs
US7432261B2 (en) 2003-04-25 2008-10-07 Gilead Sciences, Inc. Anti-inflammatory phosphonate compounds
US7427636B2 (en) 2003-04-25 2008-09-23 Gilead Sciences, Inc. Inosine monophosphate dehydrogenase inhibitory phosphonate compounds
KR20060022647A (ko) 2003-04-25 2006-03-10 길리애드 사이언시즈, 인코포레이티드 키나아제 억제 포스포네이트 유사체
WO2005002626A2 (en) 2003-04-25 2005-01-13 Gilead Sciences, Inc. Therapeutic phosphonate compounds
EA014685B1 (ru) 2003-04-25 2010-12-30 Джилид Сайэнс, Инк. Фосфонатсодержащие антивирусные соединения (варианты) и фармацевтическая композиция на их основе
US7452901B2 (en) 2003-04-25 2008-11-18 Gilead Sciences, Inc. Anti-cancer phosphonate analogs
US7407965B2 (en) 2003-04-25 2008-08-05 Gilead Sciences, Inc. Phosphonate analogs for treating metabolic diseases
HUE029877T2 (en) 2003-05-30 2017-04-28 Gilead Pharmasset Llc Modified fluorinated nucleoside analogues
WO2005044279A1 (en) 2003-10-24 2005-05-19 Gilead Sciences, Inc. Purine nucleoside phosphonate conjugates
WO2005044308A1 (en) 2003-10-24 2005-05-19 Gilead Sciences, Inc. Phosphonate analogs of antimetabolites
BRPI0417988A (pt) 2003-12-22 2007-04-27 Gilead Sciences Inc análogos de fosfonato antivirais
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
AU2005330489B2 (en) 2004-07-27 2011-08-25 Gilead Sciences, Inc. Nucleoside phosphonate conjugates as anti HIV agents
AU2006298677A1 (en) * 2005-10-06 2007-04-12 Innate Pharma Phosphoantigen salts of organic bases and methods for their crystallization
WO2008150438A1 (en) * 2007-06-01 2008-12-11 Luitpold Pharmaceuticals, Inc. Pmea lipid conjugates
CA2714198A1 (en) * 2008-02-15 2009-08-20 Microdose Therapeutx, Inc. Methods of making nucleoside tetraphosphate analogs
US8658617B2 (en) 2008-07-08 2014-02-25 Gilead Sciences, Inc. Salts of HIV inhibitor compounds
EP2447274B1 (en) 2008-10-24 2017-10-04 Ionis Pharmaceuticals, Inc. Oligomeric compounds and methods
WO2011139699A2 (en) 2010-04-28 2011-11-10 Isis Pharmaceuticals, Inc. 5' modified nucleosides and oligomeric compounds prepared therefrom
US9156873B2 (en) 2010-04-28 2015-10-13 Isis Pharmaceuticals, Inc. Modified 5′ diphosphate nucleosides and oligomeric compounds prepared therefrom
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JP2016512846A (ja) * 2013-03-13 2016-05-09 ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド Ｒａｓ阻害剤およびその使用
WO2017120508A1 (en) 2016-01-08 2017-07-13 Arcus Biosciences, Inc. Modulators of 5'-nucleotidase, ecto and the use thereof
WO2018094148A1 (en) * 2016-11-18 2018-05-24 Arcus Biosciences, Inc. Inhibitors of cd73-mediated immunosuppression
SI3661937T1 (sl) 2017-08-01 2021-11-30 Gilead Sciences, Inc. Kristalinične oblike etil((S)-((((2R,5R)-5-(6-amino-9H-purin-9-IL)-4- fluoro-2,5-dihidrofuran-2-IL)oksi)metil)(fenoksi)fosforil)-L-alaninata (GS-9131) za zdravljenje virusnih okužb
WO2020210970A1 (en) * 2019-04-16 2020-10-22 Bioardis Llc Imidazotriazine derivatives as cd73 inhibitors
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992011268A1 (en) * 1990-12-20 1992-07-09 Leiras Oy Novel methylenebisphosphonic acid derivatives
DE4341161A1 (de) * 1993-12-02 1995-06-08 Michael Prof Dr Zeppezauer Membrangängiger Wirkstoff zur Störung der DNA-Biosynthese
WO1996000585A1 (fr) * 1994-06-30 1996-01-11 Commissariat A L'energie Atomique Conjugues d'analogues de diphosphates ou triphosphates

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US5569650A (en) * 1993-06-11 1996-10-29 Sloan-Kettering Institute For Cancer Research C-nucleoside isosters of analogs thereof and pharmaceutical compositions
BR9712285A (pt) 1996-10-09 2001-11-20 Pharmasset Ltd Tetrafosfonato bicìclico de trianidridas

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992011268A1 (en) * 1990-12-20 1992-07-09 Leiras Oy Novel methylenebisphosphonic acid derivatives
DE4341161A1 (de) * 1993-12-02 1995-06-08 Michael Prof Dr Zeppezauer Membrangängiger Wirkstoff zur Störung der DNA-Biosynthese
WO1996000585A1 (fr) * 1994-06-30 1996-01-11 Commissariat A L'energie Atomique Conjugues d'analogues de diphosphates ou triphosphates

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Title
J.MED.CHEM 1986M29,1726-1731 1986-01-01 *
J.MED.CHEM 1986先29言,1726,15,149，张账东 1996-03-01 *
NUCLEOSIAOS AND NUCLEOTIAES 1996,15,149,165 1996-03-01 *

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EP0934325A1 (en) 1999-08-11
BR9712285A (pt) 2001-11-20
DE69729877D1 (de) 2004-08-19
WO1998015563A1 (en) 1998-04-16
KR20000049026A (ko) 2000-07-25
US6326490B1 (en) 2001-12-04
CA2268434A1 (en) 1998-04-16
US6713623B2 (en) 2004-03-30
US20020161220A1 (en) 2002-10-31
JP2001501952A (ja) 2001-02-13
ATE271058T1 (de) 2004-07-15
AU4815197A (en) 1998-05-05
CN1239964A (zh) 1999-12-29
PT934325E (pt) 2004-10-29
KR100560182B1 (ko) 2006-03-13
EP0934325B1 (en) 2004-07-14
EP0934325A4 (en) 2000-08-16
ES2225958T3 (es) 2005-03-16
JP4118958B2 (ja) 2008-07-16
DE69729877T2 (de) 2005-07-14
CA2268434C (en) 2007-05-01

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