CS264222B1 - N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them - Google Patents
N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them Download PDFInfo
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- CS264222B1 CS264222B1 CS865469A CS546986A CS264222B1 CS 264222 B1 CS264222 B1 CS 264222B1 CS 865469 A CS865469 A CS 865469A CS 546986 A CS546986 A CS 546986A CS 264222 B1 CS264222 B1 CS 264222B1
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- compounds
- derivatives
- bases
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- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 title claims abstract description 12
- 238000000034 method Methods 0.000 title abstract description 6
- 239000002585 base Substances 0.000 claims description 24
- -1 pyrimidin-1-yl Chemical group 0.000 claims description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000000848 adenin-9-yl group Chemical group [H]N([H])C1=C2N=C([H])N(*)C2=NC([H])=N1 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000004543 purin-7-yl group Chemical group N1=CN=C2N=CN(C2=C1)* 0.000 claims description 2
- 125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 56
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 20
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- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 125000000845 uracil-1-yl group Chemical group [*]N1C(=O)N([H])C(=O)C([H])=C1[H] 0.000 description 1
- 229960003636 vidarabine Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
-
- 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
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
-
- 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
-
- 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
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6509—Six-membered rings
- C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (24)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CS865469A CS264222B1 (en) | 1986-07-18 | 1986-07-18 | N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them |
NZ221100A NZ221100A (en) | 1986-07-18 | 1987-07-16 | N-phosphonylmethoxyalkyl pyrimidines and purines and pharmaceutical compositions thereof |
IE194487A IE60117B1 (en) | 1986-07-18 | 1987-07-17 | N-phosphonylmethoxyalkyl derivatives of pyrimidine and purine bases, methods for their preparation and pharmaceutical compositions therefrom with antiviral activity |
CA000542404A CA1340856C (en) | 1986-07-18 | 1987-07-17 | N-phosphonylmethoxyalkyl pyrimidines and purines and therapeutic application thereof |
AU75759/87A AU600002B2 (en) | 1986-07-18 | 1987-07-17 | N-phosphonylmethoxyalkyl pyrimidines and purines and therapeutic application thereof |
DK373487A DK170646B1 (da) | 1986-07-18 | 1987-07-17 | N-fosfonylmetoxyalkylderivater af pyrimidinbaser og purinbaser, fremgangsmåder til fremstilling heraf, samt lægemiddelpræparat med antiviral virkning indeholdende et sådant derivat |
ES198787110399T ES2036194T3 (es) | 1986-07-18 | 1987-07-17 | Derivados n-fosfonilmetoxialquilicos de bases de pirimidina y purina, metodos para su preparacion y composiciones farmaceuticas basadas en ellos, con actividad antivirica. |
DE1997175085 DE19775085I2 (de) | 1986-07-18 | 1987-07-17 | N-Phosphonylmethoxyalkyl-Derivate von Pyrimidin- und Purinbasen, Verfahren zu ihrer Herstellung und pharmazeutische Zusammensetzungen mit antiviraler Wirkung, die sie enthalten. |
US07/074,900 US5142051A (en) | 1986-07-18 | 1987-07-17 | N-phosphonylmethoxyalkyl derivatives of pyrimidine and purine bases and a therapeutical composition therefrom with antiviral activity |
FI873165A FI86856C (fi) | 1986-07-18 | 1987-07-17 | Foerfarande foer framstaellning av n-fosfonylmetoxialkylpyrimidiner och -puriner |
EP87110399A EP0253412B1 (en) | 1986-07-18 | 1987-07-17 | N-phosphonylmethoxyalkyl derivatives of pyrimidine and purine bases, methods for their preparation and pharmaceutical compositions therefrom with antiviral activity |
ZA875283A ZA875283B (en) | 1986-07-18 | 1987-07-17 | N-phosphonylmethoxyalkyl pyrimidines and purines and therapeutic application thereof |
AT87110399T ATE57932T1 (de) | 1986-07-18 | 1987-07-17 | N-phosphonylmethoxyalkyl-derivate von pyrimidin- und purinbasen, verfahren zu ihrer herstellung und pharmazeutische zusammensetzungen mit antiviraler wirkung, die sie enthalten. |
DE8787110399T DE3765864D1 (de) | 1986-07-18 | 1987-07-17 | N-phosphonylmethoxyalkyl-derivate von pyrimidin- und purinbasen, verfahren zu ihrer herstellung und pharmazeutische zusammensetzungen mit antiviraler wirkung, die sie enthalten. |
IL83235A IL83235A (en) | 1986-07-18 | 1987-07-17 | N-phosphonylmethoxyalkyl pyrimidines and purines and therapeutic application thereof |
KR87007844A KR950004179B1 (en) | 1986-07-18 | 1987-07-18 | N-phosphonylmethoxyalkye derivatives of pyrimidine and purine bases and a therapeutical composition therefrom with antiviral activity |
JP62179877A JPH0822866B2 (ja) | 1986-07-18 | 1987-07-18 | プリンおよびピリミジン塩基のn−ホスホニルメトキシアルキル誘導体 |
EG42/87A EG18273A (en) | 1986-07-18 | 1987-07-19 | N-phosphonylmethoxyalkyl pyrimidines and purines and therapeutic application thereof |
PT85354A PT85354B (pt) | 1986-07-18 | 1987-07-20 | Processo de preparacao de derivados n-fosfonilmetoxialquilo de bases pirimidina e purina e de composicoes farmaceuticas que os contem |
GR90400937T GR3002534T3 (en) | 1986-07-18 | 1990-11-19 | N-phosphonylmethoxyalkyl derivatives of pyrimidine and purine bases, methods for their preparation and pharmaceutical compositions therefrom with antiviral activity |
US08/320,591 US5641763A (en) | 1986-07-18 | 1994-10-11 | N-phosphonylmethoxyalkyl derivatives of pyrimdine and purine bases and a therapeutical composition therefrom with antiviral activity |
US08/412,398 US5869467A (en) | 1986-07-18 | 1995-03-28 | 9-(2-phosphonylmethoxyethyl) guanine |
NL970036C NL970036I2 (nl) | 1986-07-18 | 1997-10-01 | N-fosfonylmethoxyalkylderivaten van pyrimidine en purinebasen, werkwijze voor de bereiding hiervan en farmaceutische samenstellingen hiervan met een antivirale activiteit. |
LU90155C LU90155I2 (fr) | 1986-07-18 | 1997-10-21 | Vistide - cidofovir 75 mg/ml |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CS865469A CS264222B1 (en) | 1986-07-18 | 1986-07-18 | N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them |
Publications (2)
Publication Number | Publication Date |
---|---|
CS546986A1 CS546986A1 (en) | 1988-08-16 |
CS264222B1 true CS264222B1 (en) | 1989-06-13 |
Family
ID=5399635
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CS865469A CS264222B1 (en) | 1986-07-18 | 1986-07-18 | N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them |
Country Status (21)
Country | Link |
---|---|
US (3) | US5142051A (pt) |
EP (1) | EP0253412B1 (pt) |
JP (1) | JPH0822866B2 (pt) |
KR (1) | KR950004179B1 (pt) |
AT (1) | ATE57932T1 (pt) |
AU (1) | AU600002B2 (pt) |
CA (1) | CA1340856C (pt) |
CS (1) | CS264222B1 (pt) |
DE (2) | DE19775085I2 (pt) |
DK (1) | DK170646B1 (pt) |
EG (1) | EG18273A (pt) |
ES (1) | ES2036194T3 (pt) |
FI (1) | FI86856C (pt) |
GR (1) | GR3002534T3 (pt) |
IE (1) | IE60117B1 (pt) |
IL (1) | IL83235A (pt) |
LU (1) | LU90155I2 (pt) |
NL (1) | NL970036I2 (pt) |
NZ (1) | NZ221100A (pt) |
PT (1) | PT85354B (pt) |
ZA (1) | ZA875283B (pt) |
Families Citing this family (83)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CS264222B1 (en) * | 1986-07-18 | 1989-06-13 | Holy Antonin | N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them |
AU613592B2 (en) * | 1986-11-18 | 1991-08-08 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Antiviral phosophonomethoxy-alkyene purine and pyrimide derivatives |
US5650510A (en) * | 1986-11-18 | 1997-07-22 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Antiviral phosphonomethoxyalkylene purine and pyrimidine derivatives |
JPH0217199A (ja) * | 1988-07-05 | 1990-01-22 | Japan Tobacco Inc | 2’−デオキシ−β−アデノシンの製造方法 |
US5688778A (en) * | 1989-05-15 | 1997-11-18 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Nucleoside analogs |
US5302585A (en) * | 1990-04-20 | 1994-04-12 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Use of chiral 2-(phosphonomethoxy)propyl guanines as antiviral agents |
ATE124050T1 (de) * | 1990-04-20 | 1995-07-15 | Acad Of Science Czech Republic | Chirale 2-(phosphonomethoxy)propyl-guanine als antivirale agentien. |
CZ285420B6 (cs) * | 1990-04-24 | 1999-08-11 | Ústav Organické Chemie A Biochemie Avčr | N-(3-Fluor-2-fosfonylmethoxypropyl)deriváty purinových a pyrimidinových heterocyklických bazí, způsoby jejich přípravy a použití |
CS387190A3 (en) * | 1990-08-06 | 1992-03-18 | Ustav Organicke Chemie A Bioch | (2r)-2-/di(2-propyl)phosphonylmethoxy/-3-p-toluenesulfonyloxy -1- trimethylacetoxypropane and process for preparing thereof |
DE69132276T2 (de) * | 1990-08-10 | 2001-03-01 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic, Prag/Praha | Verfahren zur herstellung von nukleotiden |
DE69129650T2 (de) * | 1990-09-14 | 1999-03-25 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic, Prag/Praha | Wirkstoffvorläufer von Phosphonaten |
US5208221A (en) * | 1990-11-29 | 1993-05-04 | Bristol-Myers Squibb Company | Antiviral (phosphonomethoxy) methoxy purine/pyrimidine derivatives |
KR0184530B1 (ko) * | 1991-10-11 | 1999-05-15 | 카렐 마르티넥 | 항비루스 비고리 포스포노메톡시알킬치환, 알켄일 및 알킨일 퓨린 및 피리미딘 유도체 |
US6057305A (en) | 1992-08-05 | 2000-05-02 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Antiretroviral enantiomeric nucleotide analogs |
US5817647A (en) * | 1993-04-01 | 1998-10-06 | Merrell Pharmaceuticals Inc. | Unsaturated acetylene phosphonate derivatives of purines |
US5514798A (en) * | 1993-06-02 | 1996-05-07 | Gilead Sciences, Inc. | Method and cyclic carbonates for nucleotide analogues |
US5798340A (en) * | 1993-09-17 | 1998-08-25 | Gilead Sciences, Inc. | Nucleotide analogs |
JPH09506333A (ja) * | 1993-09-17 | 1997-06-24 | ギリアード サイエンシーズ,インコーポレイテッド | 治療化合物の投薬方法 |
US5656745A (en) * | 1993-09-17 | 1997-08-12 | Gilead Sciences, Inc. | Nucleotide analogs |
US5502177A (en) * | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
US5468752A (en) * | 1994-04-04 | 1995-11-21 | Freeman; William R. | Treatment of conditions of abnormally increased intraocular pressure by administration of HPMPC and related phosphonylmethoxyalkylcytosines |
JPH09511507A (ja) * | 1994-04-04 | 1997-11-18 | フリーマン,ウイリアム・アール | 上昇した眼圧を治療するためのホスホニルメトキシアルキルヌクレオシドの使用 |
US5977061A (en) * | 1995-04-21 | 1999-11-02 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | N6 - substituted nucleotide analagues and their use |
US5717095A (en) * | 1995-12-29 | 1998-02-10 | Gilead Sciences, Inc. | Nucleotide analogs |
US6093816A (en) | 1996-06-27 | 2000-07-25 | Isis Pharmaceuticals, Inc. | Cationic lipids |
US5922695A (en) * | 1996-07-26 | 1999-07-13 | Gilead Sciences, Inc. | Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability |
DK1256584T3 (da) * | 1997-07-25 | 2004-12-06 | Gilead Sciences Inc | Fremgangsmåde til fremstilling af adefovir-dipivoxil |
EP1380303B1 (en) | 1998-11-02 | 2008-09-17 | Gilead Sciences, Inc. | Combination therapy to treat hepatitis B virus |
US6407077B1 (en) | 1998-11-05 | 2002-06-18 | Emory University | β-L nucleosides for the treatment of HIV infection |
US7205404B1 (en) * | 1999-03-05 | 2007-04-17 | Metabasis Therapeutics, Inc. | Phosphorus-containing prodrugs |
ATE322494T1 (de) * | 2000-01-07 | 2006-04-15 | Universitaire Instelling Antwe | Purin derivate, ihre herstellung und verwendung |
AUPQ806700A0 (en) * | 2000-06-08 | 2000-07-06 | Commonwealth Scientific And Industrial Research Organisation | Antiviral agents |
EP2682397B1 (en) | 2000-07-21 | 2017-04-19 | Gilead Sciences, Inc. | Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same |
CA2439831C (en) * | 2001-03-01 | 2010-01-12 | Triangle Pharmaceuticals, Inc. | Polymorphic and other crystalline forms of cis-ftc |
ES2564144T3 (es) * | 2001-06-29 | 2016-03-18 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Derivados de 6-[2-(fosfonometoxi)alcoxi] pirimidina que tienen actividad antivírica |
US7247621B2 (en) * | 2002-04-30 | 2007-07-24 | Valeant Research & Development | Antiviral phosphonate compounds and methods therefor |
EP1532157A4 (en) | 2002-05-13 | 2009-02-25 | Metabasis Therapeutics Inc | NEW PRODRUGS FROM PMEA TO PHOSPHONIC ACID BASE AND ITS ANALOG |
US7193081B2 (en) * | 2002-05-13 | 2007-03-20 | Metabasis Therapeutics, Inc. | Process for preparation of cyclic prodrugs of PMEA and PMPA |
AP2089A (en) | 2003-01-14 | 2010-01-11 | Gilead Sciences Inc | Compositions and methods for combination antiviraltherapy |
NZ543864A (en) | 2003-06-16 | 2009-10-30 | Leuven K U Res & Dev | Pyrimidine compounds having phosphonate groups as antiviral nucleotide analogs |
US20050080053A1 (en) * | 2003-08-29 | 2005-04-14 | Biocryst Pharmaceuticals, Inc. | Nucleosides, preparation thereof and use as inhibitors of RNA viral polymerases |
US20070269420A1 (en) * | 2003-11-24 | 2007-11-22 | Chunduru Srinivas K | Compounds, Compositions and Methods for Treatment and Prophylaxis of Hepatitis C Viral Infections and Associated Diseases |
WO2005090370A1 (en) * | 2004-02-05 | 2005-09-29 | The Regents Of The University Of California | Pharmacologically active agents containing esterified phosphonates and methods for use thereof |
WO2005107742A1 (en) | 2004-05-05 | 2005-11-17 | Yale University | Novel antiviral helioxanthin analogs |
CA2565966A1 (en) * | 2004-06-08 | 2005-12-29 | Metabasis Therapeutics, Inc. | Lewis acid mediated synthesis of cyclic esters |
EP1831235B1 (en) * | 2004-12-16 | 2013-02-20 | The Regents of The University of California | Lung-targeted drugs |
US20090156545A1 (en) * | 2005-04-01 | 2009-06-18 | Hostetler Karl Y | Substituted Phosphate Esters of Nucleoside Phosphonates |
WO2006110656A2 (en) * | 2005-04-08 | 2006-10-19 | Chimerix, Inc. | Compounds, compositions and methods for the treatment of viral infections and other medical disorders |
EP1868628B1 (en) | 2005-04-08 | 2014-06-11 | Chimerix, Inc. | Compounds, compositions and methods for the treatment of poxvirus infections |
TWI471145B (zh) | 2005-06-13 | 2015-02-01 | Bristol Myers Squibb & Gilead Sciences Llc | 單一式藥學劑量型 |
TWI375560B (en) * | 2005-06-13 | 2012-11-01 | Gilead Sciences Inc | Composition comprising dry granulated emtricitabine and tenofovir df and method for making the same |
CN100526315C (zh) | 2005-06-16 | 2009-08-12 | 浙江医药股份有限公司新昌制药厂 | N2-喹啉或异喹啉取代的嘌呤衍生物及其制备方法和其用途 |
EP2305697A3 (en) | 2005-07-25 | 2011-07-27 | Intermune, Inc. | Macrocyclic inhibitors of Hepatitis C virus replication |
JP2009511595A (ja) | 2005-10-11 | 2009-03-19 | インターミューン・インコーポレーテッド | C型肝炎ウイルスの複製を阻害する化合物および方法 |
US8076303B2 (en) | 2005-12-13 | 2011-12-13 | Spring Bank Pharmaceuticals, Inc. | Nucleotide and oligonucleotide prodrugs |
FR2908133B1 (fr) * | 2006-11-08 | 2012-12-14 | Centre Nat Rech Scient | Nouveaux analogues de nucleotides comme molecules precurseurs d'antiviraux |
GB0709408D0 (en) * | 2007-05-16 | 2007-06-27 | Katholleke Universiteit Leuven | Anti-col herpes virus compounds |
US20090181931A1 (en) * | 2008-01-16 | 2009-07-16 | Oncolys Biopharma, Inc. | Antiviral activity of cidofovir against oncolytic viruses |
WO2009094190A2 (en) | 2008-01-25 | 2009-07-30 | Chimerix, Inc. | Methods of treating viral infections |
TWI444384B (zh) | 2008-02-20 | 2014-07-11 | Gilead Sciences Inc | 核苷酸類似物及其在治療惡性腫瘤上的用途 |
US20110059921A1 (en) * | 2008-03-27 | 2011-03-10 | Ektar Therapeutics | Oligomer-Nitrogenous Base Conjugates |
MX2010011306A (es) * | 2008-04-15 | 2010-11-09 | Intermune Inc | Nuevos inhibidores macrociclicos de la replicacion del virus de la hepatitis c. |
EP2358736A1 (en) * | 2008-10-15 | 2011-08-24 | Intermune, Inc. | Therapeutic antiviral peptides |
WO2011011519A1 (en) | 2009-07-21 | 2011-01-27 | Chimerix, Inc. | Compounds, compositions and methods for treating ocular conditions |
BR112012002551A2 (pt) | 2009-08-03 | 2017-06-13 | Chimerix Inc | composição e métodos de tratamento de infecções virais e tumores induzidos por vírus |
TW201116540A (en) * | 2009-10-01 | 2011-05-16 | Intermune Inc | Therapeutic antiviral peptides |
DK2534150T3 (en) | 2010-02-12 | 2017-06-12 | Chimerix Inc | METHODS OF TREATING VIRUS INFECTION |
EP2371369A1 (en) | 2010-04-01 | 2011-10-05 | Institut Gustave Roussy (IGR) | EGFR inhibitor and antiviral agent for simultaneous, separate or sequential use in the treatment and/or prevention and/or palliation of cancer |
EP2563367A4 (en) | 2010-04-26 | 2013-12-04 | Chimerix Inc | METHODS OF TREATING RETROVIRAL INFECTIONS AND ASSOCIATED DOSAGE REGIMES |
BR112013014485B1 (pt) | 2010-12-10 | 2021-03-30 | Sigmapharm Laboratories, Llc | Composições farmacêuticas compreendendo pró-fármacos análogos de nucleotídeos de fosfonato ativos por via oral e sistema de embalagem de recipiente/fechamento contendo as ditas composições |
JP2014505076A (ja) * | 2011-01-27 | 2014-02-27 | ザ トラスティーズ オブ プリンストン ユニバーシティ | 抗ウイルス剤としてのmTORキナーゼの阻害剤 |
WO2012138954A1 (en) | 2011-04-07 | 2012-10-11 | Johnson Matthey Public Limited Company | Forms of cidofovir |
ES2874774T3 (es) | 2011-12-22 | 2021-11-05 | Geron Corp | Análogos de guanina como sustratos de telomerasa y afectores de la longitud de los telómeros |
EP2846788A1 (en) | 2012-05-11 | 2015-03-18 | Akron Molecules AG | Use of compounds for the treatment of pain |
AU2013340559B2 (en) | 2012-10-29 | 2018-03-15 | Cipla Limited | Antiviral phosphonate analogues and process for preparation thereof |
RS57796B1 (sr) | 2013-03-15 | 2018-12-31 | Univ California | Diestri acikličnog nukleozid fosfonata |
AU2015217221A1 (en) | 2014-02-13 | 2016-08-11 | Ligand Pharmaceuticals, Inc. | Prodrug compounds and their uses |
US9994600B2 (en) | 2014-07-02 | 2018-06-12 | Ligand Pharmaceuticals, Inc. | Prodrug compounds and uses therof |
US9493493B2 (en) | 2014-09-15 | 2016-11-15 | The Regents Of The University Of California | Nucleotide analogs |
EP3875462A1 (en) | 2015-09-15 | 2021-09-08 | The Regents of The University of California | Nucleotide analogs |
US10745427B2 (en) | 2016-03-09 | 2020-08-18 | Janssen Biopharma, Inc. | Acyclic antivirals |
AU2019207625A1 (en) | 2018-01-09 | 2020-07-30 | Ligand Pharmaceuticals, Inc. | Acetal compounds and therapeutic uses thereof |
US20230218644A1 (en) | 2020-04-16 | 2023-07-13 | Som Innovation Biotech, S.A. | Compounds for use in the treatment of viral infections by respiratory syndrome-related coronavirus |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU521577B2 (en) * | 1977-02-24 | 1982-04-22 | Wellcome Foundation Limited, The | 9-hydroxyethoxymethyl guanine phosphates |
US4287188A (en) * | 1977-02-24 | 1981-09-01 | Burroughs Wellcome Co. | Purine derivatives |
DE2909709A1 (de) * | 1979-03-12 | 1980-09-25 | Kailash Kumar Dr Gauri | Verfahren zur herstellung von nucleotidderivaten, neue nucleotidderivate und daraus hergestellte arzneimittel |
EP0105486A3 (en) * | 1982-09-30 | 1984-05-16 | Syntex (U.S.A.) Inc. | 1-monophosphate esters, 1,3-bisphosphate esters and cyclic phosphate esters of 9-(1,3-dihydroxy-2-propoxymethyl)-guanine as antiviral agents |
CS233665B1 (en) * | 1983-01-06 | 1985-03-14 | Antonin Holy | Processing of isomere o-phosphonylmethylderivative of anantiomere racemic vicinal diene |
US5047533A (en) * | 1983-05-24 | 1991-09-10 | Sri International | Acyclic purine phosphonate nucleotide analogs |
IL72173A0 (en) * | 1983-06-24 | 1984-10-31 | Merck & Co Inc | Guanine derivatives,their preparation and pharmaceutical compositions containing them |
US4670424A (en) * | 1983-09-19 | 1987-06-02 | Merck & Co., Inc. | Cyclic pyrophosphates of purine and pyrimidine acyclonucleosides |
US4590269A (en) * | 1984-03-29 | 1986-05-20 | Syntex (U.S.A.) Inc. | Process for preparing the cyclic phosphate ester of substituted 9-(1,3-dihydroxy-2-propoxymethyl)purines |
US4579849A (en) * | 1984-04-06 | 1986-04-01 | Merck & Co., Inc. | N-alkylguanine acyclonucleosides as antiviral agents |
CS263951B1 (en) * | 1985-04-25 | 1989-05-12 | Antonin Holy | 9-(phosponylmethoxyalkyl)adenines and method of their preparation |
CS263952B1 (en) * | 1985-04-25 | 1989-05-12 | Holy Antonin | Remedy with antiviral effect |
CS264222B1 (en) * | 1986-07-18 | 1989-06-13 | Holy Antonin | N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them |
AU613592B2 (en) * | 1986-11-18 | 1991-08-08 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Antiviral phosophonomethoxy-alkyene purine and pyrimide derivatives |
CA1330794C (en) * | 1987-03-27 | 1994-07-19 | Phillip Frost | Anti-viral compounds, dosage forms and methods |
-
1986
- 1986-07-18 CS CS865469A patent/CS264222B1/cs not_active IP Right Cessation
-
1987
- 1987-07-16 NZ NZ221100A patent/NZ221100A/xx unknown
- 1987-07-17 CA CA000542404A patent/CA1340856C/en not_active Expired - Lifetime
- 1987-07-17 FI FI873165A patent/FI86856C/fi not_active IP Right Cessation
- 1987-07-17 ES ES198787110399T patent/ES2036194T3/es not_active Expired - Lifetime
- 1987-07-17 DE DE1997175085 patent/DE19775085I2/de active Active
- 1987-07-17 AT AT87110399T patent/ATE57932T1/de active
- 1987-07-17 AU AU75759/87A patent/AU600002B2/en not_active Expired
- 1987-07-17 DE DE8787110399T patent/DE3765864D1/de not_active Expired - Lifetime
- 1987-07-17 EP EP87110399A patent/EP0253412B1/en not_active Expired - Lifetime
- 1987-07-17 ZA ZA875283A patent/ZA875283B/xx unknown
- 1987-07-17 DK DK373487A patent/DK170646B1/da not_active IP Right Cessation
- 1987-07-17 IE IE194487A patent/IE60117B1/en not_active IP Right Cessation
- 1987-07-17 IL IL83235A patent/IL83235A/xx not_active IP Right Cessation
- 1987-07-17 US US07/074,900 patent/US5142051A/en not_active Expired - Lifetime
- 1987-07-18 KR KR87007844A patent/KR950004179B1/ko not_active IP Right Cessation
- 1987-07-18 JP JP62179877A patent/JPH0822866B2/ja not_active Expired - Lifetime
- 1987-07-19 EG EG42/87A patent/EG18273A/xx active
- 1987-07-20 PT PT85354A patent/PT85354B/pt unknown
-
1990
- 1990-11-19 GR GR90400937T patent/GR3002534T3/el unknown
-
1994
- 1994-10-11 US US08/320,591 patent/US5641763A/en not_active Expired - Lifetime
-
1995
- 1995-03-28 US US08/412,398 patent/US5869467A/en not_active Expired - Lifetime
-
1997
- 1997-10-01 NL NL970036C patent/NL970036I2/nl unknown
- 1997-10-21 LU LU90155C patent/LU90155I2/fr unknown
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Legal Events
Date | Code | Title | Description |
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IF00 | In force as of 2000-06-30 in czech republic | ||
MK4A | Patent expired |
Effective date: 20010718 |