CA2416757A1 - Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same - Google Patents

Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same Download PDF

Info

Publication number
CA2416757A1
CA2416757A1 CA002416757A CA2416757A CA2416757A1 CA 2416757 A1 CA2416757 A1 CA 2416757A1 CA 002416757 A CA002416757 A CA 002416757A CA 2416757 A CA2416757 A CA 2416757A CA 2416757 A1 CA2416757 A1 CA 2416757A1
Authority
CA
Canada
Prior art keywords
compound
amino
solvates
hydroxyl
salts
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
CA002416757A
Other languages
French (fr)
Other versions
CA2416757C (en
Inventor
Mark W. Becker
Harlan H. Chapman
Tomas Cihlar
Eugene J. Eisenberg
Gong-Xin He
Michael R. Kernan
William A. Lee
Ernest J. Prisbe
John C. Rohloff
Mark L. Sparacino
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gilead Sciences Inc
Original Assignee
Individual
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22821718&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2416757(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Individual filed Critical Individual
Priority to CA2725819A priority Critical patent/CA2725819C/en
Publication of CA2416757A1 publication Critical patent/CA2416757A1/en
Application granted granted Critical
Publication of CA2416757C publication Critical patent/CA2416757C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

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
    • 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
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • 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
    • 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
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • 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
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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 System
    • 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
    • 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
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/18—Testing for antimicrobial activity of a material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity

Abstract

A novel method is provided for screening prodrugs of methoxyphosphonate nucleotide analogues to identify prodrugs selectively targeting desired tissues with antiviral or antitumor activity. This method has led to the identification of novel mixed ester-amidates of PMPA for retroviral or hepadnaviral therapy, including compounds of structure (5a) having substituent groups as defined herein. Compositions of these novel compounds in pharmaceutically acceptable excipients and their use in therapy and prophylaxis are provided. Also provided is an improved method for the use of magnesium alkoxide for the preparation of starting materials and compounds for use herein.

Claims (12)

1. A compound having the structure (1):

where Ra is H or methyl, and chirally enriched compositions thereof, salts, their free base and solvates thereof.
2. A compound having the structure (2):

and its enriched diasteromers, salts, free base and solvates.
3. A diastereomerically enriched compound having the structure (3):

which is substantially free of the diastereomer (4):

wherein R1 is an oxyester which is hydrolyzable in vivo or, hydroxyl;
B is a heterocyclic base;
R2 is hydroxyl, or the residue of an amino acid bonded to the P atom through an amino group of the amino acid and having each carboxy substituent of the amino acid optionally esterified, but not both of R1 and R2 are hydroxyl;

E is -(CH2)2-, -CH(CH3)CH2-, -CH(CH2F)CH2-, -CH(CH2OH)CH2-, -CH(CH=CH2)CH2-, -CH(C.ident.CH)CH2-, -CH(CH2N3)CH2-, -CH(R6)OCH(R6')-, -CH(R9)CH2O- or -CH(R8)O-, wherein the right hand bond is linked to the heterocyclic base;
the broken line represents an optional double bond;

R4 and R5 are independently hydrogen, hydroxyl, halo, amino or a subtitutent having 1-5 carbon atoms selected from acyloxy, alkyoxy, alkylthio, alkylamino and dialkylamino;

R6 and R6' are independently H, C1-C6 alkyl, C1-C6 hydroxyalkyl, or C2-C7 alkanoyl;
R7 is independently H, C1-C6 alkyl, or are taken together to form -O- or -CH2-;

R8 is H, C1-C6 alkyl, C1-C6 hydroxyalkyl or C1-C6 haloalkyl; and R9 is H, hydroxymethyl or acyloxymethyl;
and their salts, free base, and solvates.
4. A diastereomerically enriched compound having the structure (5a):

which is substantially free of diastereomer (5b) wherein R5 is methyl or hydrogen;

R6 independently is H, alkyly alkenyl, alkynyl, aryl or arylalkyl, or R6 independently is alkyl, alkenyl, alkynyl, aryl or arylalkyl which is substituted with from 1 to 3 substituents selected from alkylamino, alkylaminoalkyl, dialkylaminoalkyl, dialkylamino, hydroxyl, oxo, halo, amino, alkylthio, alkoxy, alkoxyalkyl, aryloxy, aryloxyalkyl, arylalkoxy, arylalkoxyalkyl, haloalkyl, nitro, nitroalkyl, azido, azidoalkyl, alkylacyl, alkylacylalkyl, carboxyl, or alkylacylamino;

R7 is the side chain of any naturally-occuring or pharmaceutically acceptable amino acid and which, if the side chain comprises carboxyl, the carboxyl group is optionally esterified with an alkyl or aryl group;

R11 is amino, alkylamino, oxo, or dialkylamino; and R12 is amino or H;
and it salts, tautomers, free base and solvates.
5. A compound of structure (6):

and its salts and solvates.
6. A diastereomerically enriched compound of structure (6a):

which is substantially free of diastereomer (6b):

7. A compound of structure (7):

8. A diastereomerically enriched compound of structure (7a):

which is substantially free of diastereomer (7b)
9. A composition comprising a compound of any one of claims 1 to 8 and a pharmaceutically effective excipient.
10. The composition of claim 9, wherein the excipient is a gel.
11. The composition of claim 9, which is suitable for topical administration.
12. Use of a compound of any one of claims 1 to 8 in a therapeutically or prophylactically effective amount for antiviral therapy or prophylaxis in a subject in need of such therapy or prophylaxis.
CA2416757A 2000-07-21 2001-07-20 Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same Expired - Lifetime CA2416757C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2725819A CA2725819C (en) 2000-07-21 2001-07-20 Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US22002100P 2000-07-21 2000-07-21
US60/220,021(CIP) 2000-07-21
US60/220,021 2000-07-21
PCT/US2001/023104 WO2002008241A2 (en) 2000-07-21 2001-07-20 Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CA2725819A Division CA2725819C (en) 2000-07-21 2001-07-20 Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same

Publications (2)

Publication Number Publication Date
CA2416757A1 true CA2416757A1 (en) 2002-01-31
CA2416757C CA2416757C (en) 2011-02-15

Family

ID=22821718

Family Applications (3)

Application Number Title Priority Date Filing Date
CA2725819A Expired - Lifetime CA2725819C (en) 2000-07-21 2001-07-20 Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same
CA2416757A Expired - Lifetime CA2416757C (en) 2000-07-21 2001-07-20 Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same
CA2893174A Abandoned CA2893174A1 (en) 2000-07-21 2001-07-20 Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CA2725819A Expired - Lifetime CA2725819C (en) 2000-07-21 2001-07-20 Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same

Family Applications After (1)

Application Number Title Priority Date Filing Date
CA2893174A Abandoned CA2893174A1 (en) 2000-07-21 2001-07-20 Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same

Country Status (37)

Country Link
US (10) US20020119443A1 (en)
EP (3) EP1301519B2 (en)
JP (4) JP4651264B2 (en)
KR (2) KR100749160B1 (en)
CN (2) CN1291994C (en)
AP (1) AP1466A (en)
AU (3) AU2001282941C1 (en)
BE (1) BE2016C018I2 (en)
BG (1) BG66037B1 (en)
BR (1) BRPI0112646B8 (en)
CA (3) CA2725819C (en)
CY (2) CY2016008I2 (en)
CZ (2) CZ304886B6 (en)
DK (2) DK2682397T3 (en)
EA (1) EA004926B1 (en)
EE (1) EE05366B1 (en)
ES (2) ES2536972T5 (en)
FR (1) FR16C0013I2 (en)
HK (2) HK1054238A1 (en)
HR (2) HRP20160074B1 (en)
HU (2) HU230960B1 (en)
IL (1) IL153658A0 (en)
IS (1) IS2985B (en)
LT (2) LT2682397T (en)
LU (1) LU93029I2 (en)
MX (1) MXPA03000587A (en)
NL (1) NL300803I2 (en)
NO (6) NO336718B1 (en)
NZ (3) NZ535408A (en)
OA (1) OA12393A (en)
PL (1) PL213214B1 (en)
PT (2) PT2682397T (en)
SI (2) SI1301519T1 (en)
TR (1) TR200300055T2 (en)
UA (1) UA75889C2 (en)
WO (1) WO2002008241A2 (en)
ZA (1) ZA200210271B (en)

Families Citing this family (216)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1301519B2 (en) * 2000-07-21 2021-11-10 Gilead Sciences, Inc. Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same
EA200400690A1 (en) * 2001-11-14 2005-06-30 Байокрист Фармасьютикалз, Инк. NUCLEOSIDES, THEIR PREPARATIONS AND THEIR APPLICATION AS VIRAL RNA POLYMERASE INHIBITORS
US7388002B2 (en) * 2001-11-14 2008-06-17 Biocryst Pharmaceuticals, Inc. Nucleosides, preparation thereof and use as inhibitors of RNA viral polymerases
EP1501841A2 (en) * 2002-04-26 2005-02-02 Gilead Sciences, Inc. Non nucleoside reverse transcriptase inhibitors
US20050239054A1 (en) * 2002-04-26 2005-10-27 Arimilli Murty N Method and compositions for identifying anti-HIV therapeutic compounds
CA2485702C (en) 2002-05-13 2011-07-19 Metabasis Therapeutics, Inc. Novel phosphonic acid based prodrugs of pmea and its analogues
EP1923063A3 (en) * 2003-01-14 2009-04-08 Gilead Sciences, Inc. Compositions and methods for combination antiviral therapy
US7427636B2 (en) 2003-04-25 2008-09-23 Gilead Sciences, Inc. Inosine monophosphate dehydrogenase inhibitory phosphonate compounds
US7300924B2 (en) 2003-04-25 2007-11-27 Gilead Sciences, Inc. Anti-infective phosphonate analogs
US20050261237A1 (en) * 2003-04-25 2005-11-24 Boojamra Constantine G Nucleoside phosphonate analogs
US7432261B2 (en) 2003-04-25 2008-10-07 Gilead Sciences, Inc. Anti-inflammatory phosphonate compounds
US7407965B2 (en) * 2003-04-25 2008-08-05 Gilead Sciences, Inc. Phosphonate analogs for treating metabolic diseases
WO2005002626A2 (en) * 2003-04-25 2005-01-13 Gilead Sciences, Inc. Therapeutic phosphonate compounds
US20090247488A1 (en) * 2003-04-25 2009-10-01 Carina Cannizzaro Anti-inflammatory phosphonate compounds
US7452901B2 (en) 2003-04-25 2008-11-18 Gilead Sciences, Inc. Anti-cancer phosphonate analogs
AU2004233897A1 (en) 2003-04-25 2004-11-11 Gilead Sciences, Inc. Kinase inhibitor phosphonate conjugates
US7470724B2 (en) * 2003-04-25 2008-12-30 Gilead Sciences, Inc. Phosphonate compounds having immuno-modulatory activity
WO2004096286A2 (en) * 2003-04-25 2004-11-11 Gilead Sciences, Inc. Antiviral phosphonate analogs
CN101410120A (en) * 2003-04-25 2009-04-15 吉里德科学公司 Anti-inflammatory phosphonate compounds
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
JP2007508845A (en) 2003-10-24 2007-04-12 ギリアード サイエンシーズ， インコーポレイテッド Methods and compositions for the identification of therapeutic compounds
US20050153990A1 (en) * 2003-12-22 2005-07-14 Watkins William J. Phosphonate substituted kinase inhibitors
BRPI0418031A (en) * 2003-12-22 2007-04-17 Gilead Sciences Inc phosphonate-substituted kinase inhibitors
WO2005063751A1 (en) * 2003-12-22 2005-07-14 Gilead Sciences, Inc. 4’-substituted carbovir-and abacavir-derivatives as well as related compounds with hiv and hcv antiviral activity
DE602004028763D1 (en) * 2003-12-30 2010-09-30 Gilead Sciences Inc TE FOR THE TREATMENT OF VIRUS DISEASES
AU2005209256B2 (en) * 2004-01-21 2010-11-18 Gilead Sciences, Inc. Use of adefovir or tenofovir for inhibiting MMTV-like viruses involved in breast cancer and primary biliary cirrhosis
US8432394B1 (en) 2004-05-14 2013-04-30 Nvidia Corporation Method and system for implementing clamped z value interpolation in a raster stage of a graphics pipeline
US8416242B1 (en) 2004-05-14 2013-04-09 Nvidia Corporation Method and system for interpolating level-of-detail in graphics processors
US7079156B1 (en) 2004-05-14 2006-07-18 Nvidia Corporation Method and system for implementing multiple high precision and low precision interpolators for a graphics pipeline
US8411105B1 (en) 2004-05-14 2013-04-02 Nvidia Corporation Method and system for computing pixel parameters
JP5142716B2 (en) 2004-06-08 2013-02-13 リガンド・ファーマシューティカルズ・インコーポレイテッド Lewis acid mediated synthesis of cyclic esters
DE602005027466D1 (en) * 2004-07-27 2011-05-26 Gilead Sciences Inc NUCLEOSIDE PHOSPHONATE CONJUGATES AS ANTI HIV MEDIUM
JP2008538354A (en) * 2005-04-08 2008-10-23 キメリクス，インコーポレイテッド Compounds, compositions and methods for treating viral infections and other medical diseases
JP2008535862A (en) 2005-04-08 2008-09-04 キメリクス，インコーポレイテッド Compounds, compositions and methods for the treatment of poxvirus infections
CN100359315C (en) * 2005-05-26 2008-01-02 林维宣 Animal remedy residual ability verification sample and method for preparing same
TWI471145B (en) 2005-06-13 2015-02-01 Bristol Myers Squibb & Gilead Sciences Llc Unitary pharmaceutical dosage form
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
US8076303B2 (en) 2005-12-13 2011-12-13 Spring Bank Pharmaceuticals, Inc. Nucleotide and oligonucleotide prodrugs
CN100396689C (en) * 2006-03-07 2008-06-25 中国医学科学院医药生物技术研究所 Tenoforv monoester compounds with HIV-1/HBV virus copying inhibiting activity
WO2007136650A2 (en) 2006-05-16 2007-11-29 Gilead Sciences, Inc. Method and compositions for treating hematological malignancies
WO2008007392A2 (en) 2006-07-12 2008-01-17 Matrix Laboratories Limited Process for the preparation of tenofovir
US7951789B2 (en) * 2006-12-28 2011-05-31 Idenix Pharmaceuticals, Inc. Compounds and pharmaceutical compositions for the treatment of viral infections
US7964580B2 (en) 2007-03-30 2011-06-21 Pharmasset, Inc. Nucleoside phosphoramidate prodrugs
AU2008302676B2 (en) * 2007-06-26 2013-02-28 University Of Wyoming Research Corporation D/B/A Western Research Institute Treatment and prevention systems for acid mine drainage and halogenated contaminants
US8441497B1 (en) * 2007-08-07 2013-05-14 Nvidia Corporation Interpolation of vertex attributes in a graphics processor
AU2009206673B2 (en) * 2008-01-25 2015-04-23 Chimerix, Inc. Methods of treating viral infections
TWI444384B (en) 2008-02-20 2014-07-11 Gilead Sciences Inc Nucleotide analogues and their use in the treatment of malignancies
EP2937356A1 (en) 2008-04-25 2015-10-28 Cipla Limited Crystalline form of tenofovir disoproxil and a process for its preparation
US8173621B2 (en) 2008-06-11 2012-05-08 Gilead Pharmasset Llc Nucleoside cyclicphosphates
JP2011526893A (en) * 2008-07-02 2011-10-20 イデニク プハルマセウティカルス，インコーポレイテッド Compounds and pharmaceutical compositions for the treatment of viral infections
AP3347A (en) 2008-07-08 2015-07-31 Gilead Sciences Inc Salts of HIV inhibitor compounds
SG172361A1 (en) 2008-12-23 2011-07-28 Pharmasset Inc Nucleoside analogs
EP2376088B1 (en) 2008-12-23 2017-02-22 Gilead Pharmasset LLC 6-O-Substituted-2-amino-purine nucleoside phosphoramidates
US8716263B2 (en) * 2008-12-23 2014-05-06 Gilead Pharmasset Llc Synthesis of purine nucleosides
US8618076B2 (en) 2009-05-20 2013-12-31 Gilead Pharmasset Llc Nucleoside phosphoramidates
TWI598358B (en) 2009-05-20 2017-09-11 基利法瑪席特有限責任公司 Nucleoside phosphoramidates
WO2011011519A1 (en) 2009-07-21 2011-01-27 Chimerix, Inc. Compounds, compositions and methods for treating ocular conditions
KR101848099B1 (en) 2009-09-21 2018-04-11 길리애드 사이언시즈, 인코포레이티드 Processes and intermediates for the preparation of 1'-substituted carba-nucleoside analogs
EP2534150B1 (en) 2010-02-12 2017-04-05 Chimerix, Inc. Methods of treating viral infection
PL2552930T3 (en) 2010-03-31 2016-02-29 Gilead Pharmasset Llc Crystalline (s)-isopropyl 2-(((s)-(((2r,3r,4r,5r)-5-(2,4-dioxo-3,4-dihydropyrimidin-1-(2h)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate
PL3290428T3 (en) 2010-03-31 2022-02-07 Gilead Pharmasset Llc Tablet comprising crystalline (s)-isopropyl 2-(((s)-(((2r,3r,4r,5r)-5-(2,4-dioxo-3,4-dihydropyrimidin-1 (2h)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate
AR094621A1 (en) 2010-04-01 2015-08-19 Idenix Pharmaceuticals Inc PHARMACEUTICAL COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF VIRAL INFECTIONS
WO2011139709A2 (en) 2010-04-26 2011-11-10 Chimerix, Inc. Methods of treating retroviral infections and related dosage regimes
WO2012012465A1 (en) 2010-07-19 2012-01-26 Clarke, Michael, O'neil Hanrahan Methods for the preparation of diasteromerically pure phosphoramidate prodrugs
BR122020020745B8 (en) 2010-07-22 2023-10-31 Gilead Sciences Inc Antiviral compound for the treatment of paramyxoviridae infections and pharmaceutical composition comprising it
JP6069215B2 (en) 2010-11-30 2017-02-01 ギリアド ファーマセット エルエルシー Compound
WO2012079035A1 (en) 2010-12-10 2012-06-14 Sigmapharm Laboratories, Llc Highly stable compositions of orally active nucleotide analogues or orally active nucleotide analogue prodrugs
ZA201103820B (en) 2010-12-13 2012-01-25 Laurus Labs Private Ltd Process for the preparation of tenofovir
CN103842369A (en) 2011-03-31 2014-06-04 埃迪尼克斯医药公司 Compounds and pharmaceutical compositions for the treatment of viral infections
WO2012154698A2 (en) * 2011-05-06 2012-11-15 Mckenna Charles E Method to improve antiviral activity of nucleotide analogue drugs
JP5951757B2 (en) * 2011-05-19 2016-07-13 ギリアード サイエンシーズ， インコーポレイテッド Processes and intermediates for preparing anti-HIV agents
AU2014271320B2 (en) * 2011-08-16 2017-02-23 Gilead Sciences, Inc. Tenofovir alafenamide hemifumarate
MX336627B (en) * 2011-08-16 2016-01-26 Gilead Sciences Inc Tenofovir alafenamide hemifumarate.
PE20141056A1 (en) 2011-09-16 2014-09-05 Gilead Pharmasset Llc METHODS FOR THE TREATMENT OF HCV
AR088109A1 (en) 2011-10-07 2014-05-07 Gilead Sciences Inc METHOD FOR PREPARING ANTIVIRAL NUCLEOTIDAL ANALOGS
AU2014215976B2 (en) * 2011-10-07 2016-06-30 Gilead Sciences, Inc. Methods for preparing anti-viral nucleotide analogs
AU2016228317B2 (en) * 2011-10-07 2018-07-19 Gilead Sciences, Inc. Methods for preparing anti-viral nucleotide analogs
US8889159B2 (en) 2011-11-29 2014-11-18 Gilead Pharmasset Llc Compositions and methods for treating hepatitis C virus
ES2734495T3 (en) 2011-12-22 2019-12-10 Geron Corp Guanine analogs such as telomerase substrates and telomere length affecters
AU2012327170A1 (en) 2012-02-03 2013-08-22 Gilead Sciences, Inc. Therapeutic compounds
US20150105350A1 (en) * 2012-02-03 2015-04-16 Gilead Sciences, Inc. Combination therapy comprising tenofovir alafenamide hemifumarate and cobicistat for use in the treatment of viral infections
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
GB201215696D0 (en) * 2012-09-03 2012-10-17 Ithemba Pharmaceuticals Pty Ltd A process for the preparation of (R)-9-[2-(Phosphonometh-Oxy)propyl]adenine (PMPA)
WO2014068265A1 (en) * 2012-10-29 2014-05-08 Cipla Limited Antiviral phosphonate analogues and process for preparation thereof
CN102899327B (en) * 2012-11-06 2014-06-11 清华大学深圳研究生院 Antiviral small nucleic acid and temperature-sensitive type gel preparation and application thereof
JP6297582B2 (en) * 2012-11-16 2018-03-20 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． Purine inhibitors of human phosphatidylinositol 3-kinase delta
CN103848869B (en) * 2012-12-04 2016-12-21 上海医药工业研究院 The method preparing tenofovir
CN103848868B (en) * 2012-12-04 2017-04-12 蚌埠丰原涂山制药有限公司 method for preparing tenofovir
MD4595B1 (en) 2013-01-31 2018-10-31 Gilead Pharmasset Llc. Combination formulation of two antiviral compounds
CN104072539B (en) * 2013-03-25 2017-03-29 安徽贝克联合制药有限公司 Double (4 acetaminophenol epoxide) esters of tenofovir and preparation method thereof and its application
WO2014187314A1 (en) * 2013-05-21 2014-11-27 成都先导药物开发有限公司 Drug target capturing method
WO2014195724A1 (en) 2013-06-07 2014-12-11 Cipla Limited An efficient process for separation of diastereomers of 9-[(r)-2-[[(r,s)-[[(s)-1-(isopropoxycarbonyl)ethyl]amino]-phenoxyphosphinyl] methoxy]propyl]adenine
NZ716840A (en) 2013-08-27 2017-06-30 Gilead Pharmasset Llc Combination formulation of two antiviral compounds
WO2015040640A2 (en) * 2013-09-20 2015-03-26 Laurus Labs Private Limited An improved process for the preparation of tenofovir alafenamide or pharmaceutically acceptable salts thereof
EP2860185A1 (en) 2013-10-09 2015-04-15 Zentiva, k.s. An improved process for the preparation of Tenofovir disoproxil and pharmaceutically acceptable salts thereof
IN2013CH05455A (en) * 2013-11-27 2015-08-07 Laurus Labs Private Ltd
WO2015107451A2 (en) 2014-01-14 2015-07-23 Mylan Laboratories Ltd. Purification of tenofovir alafenamide and its intermediates
TWI660965B (en) 2014-01-15 2019-06-01 美商基利科學股份有限公司 Solid forms of tenofovir
CN104804042B (en) * 2014-01-24 2018-01-19 齐鲁制药有限公司 Phosphonate-nucleotide ester class compound, its pharmaceutical composition, Preparation method and use
US9463194B2 (en) 2014-02-05 2016-10-11 Gilead Sciences, Inc. Methods of treating patients co-infected with HIV and tuberculosis
US10449210B2 (en) 2014-02-13 2019-10-22 Ligand Pharmaceuticals Inc. Prodrug compounds and their uses
CN105814068B (en) * 2014-02-27 2017-08-04 四川海思科制药有限公司 A kind of substituted phosphoramidic acid ester derivative, its preparation method and its application
CN105001262B (en) * 2014-04-18 2017-09-01 四川海思科制药有限公司 The phosphonaminate of aryl substitution and its application medically
CN105518011B (en) * 2014-04-21 2018-07-27 四川海思科制药有限公司 The preparation method of phosphoramidic acid ester derivative Preparation Method And Their Intermediate and intermediate
CN105085571A (en) * 2014-05-20 2015-11-25 四川海思科制药有限公司 Tenofovir alafenamide compound, preparation method and purpose thereof
CN105518012B (en) * 2014-06-25 2018-03-02 四川海思科制药有限公司 A kind of substituted amino acid sulfur ester, its composition and application
EP3164136A4 (en) 2014-07-02 2018-04-04 Ligand Pharmaceuticals, Inc. Prodrug compounds and uses therof
JP2017535520A (en) * 2014-09-30 2017-11-30 ハンミ・ファイン・ケミカル・カンパニー・リミテッドＨａｎｍｉ Ｆｉｎｅ Ｃｈｅｍｉｃａｌ Ｃｏ．， Ｌｔｄ． Method for producing high purity (R) -9- [2- (phosphonomethoxy) propyl] adenine
KR101703257B1 (en) 2014-09-30 2017-02-06 한미정밀화학주식회사 Preparation method for (r)-9-[2-(phosphonomethoxy)propyl]adenine with high purity
KR101703258B1 (en) 2014-12-30 2017-02-06 한미정밀화학주식회사 Preparation method for (r)-9-[2-(phosphonomethoxy)propyl]adenine with high purity
US11311545B2 (en) 2014-10-09 2022-04-26 Board Of Regents Of The University Of Nebraska Compositions and methods for the delivery of therapeutics
TWI698444B (en) 2014-10-29 2020-07-11 美商基利科學股份有限公司 Methods for the preparation of ribosides
CN108148094A (en) * 2014-11-12 2018-06-12 四川海思科制药有限公司 A kind of tenofovir Chinese mugwort draws phenol amine fumarate crystal form C and its preparation method and application
CN104558036A (en) * 2014-12-11 2015-04-29 杭州和泽医药科技有限公司 Tenofovir alafenamide hemi-fumarate crystal form and preparation method thereof
BR112017014085A2 (en) 2015-01-03 2018-01-09 Mylan Laboratories Ltd Processes for the preparation of amorphous tenofovir alafenamide hemifumarate and a premixture thereof
US20180148774A1 (en) * 2015-05-16 2018-05-31 Godx, Inc Point of need testing device and methods of use thereof
CN106188139B (en) 2015-05-29 2020-02-18 江苏天士力帝益药业有限公司 Tenofovir monobenzyl phosphoric acid amide prodrug, preparation method and application thereof
CZ2015384A3 (en) 2015-06-05 2016-12-14 Zentiva, K.S. Tenofovir alafenamide solid forms
MA46677A (en) * 2015-06-17 2019-09-11 Gilead Sciences Inc CO-CRYSTALS, SALTS AND SOLID FORMS OF TENOFOVIR ALAFENAMIDE
SI4070788T1 (en) 2015-06-30 2023-06-30 Gilead Sciences, Inc. Pharmaceutical formulations
CA2994720C (en) 2015-08-10 2020-11-03 Merck Sharp & Dohme Corp. Antiviral beta-amino acid ester phosphodiamide compounds
TWI616452B (en) * 2015-08-26 2018-03-01 Preparation method of nucleoside analog and intermediate thereof
TWI620754B (en) * 2015-08-26 2018-04-11 Method for preparing amino phosphate derivative and preparation method thereof
TWI616453B (en) * 2015-08-27 2018-03-01 Substituted amino acid thioester compounds, materials and uses thereof
WO2017037608A1 (en) * 2015-08-28 2017-03-09 Laurus Labs Private Limited Solid forms of tenofovir alafenamide and salts thereof, processes for its preparation and pharmaceutical compositions thereof
ES2909419T3 (en) 2015-09-16 2022-05-06 Gilead Sciences Inc Methods for treating coronaviridae infections
PL3346995T3 (en) 2015-11-09 2020-03-31 Gilead Sciences, Inc. Therapeutic compositions for treatment of human immunodeficiency virus
CN106800573B (en) * 2015-11-25 2020-03-10 四川海思科制药有限公司 Nucleotide phosphonate monohydrate, preparation method and medical application thereof
WO2017100108A1 (en) 2015-12-10 2017-06-15 Merck Sharp & Dohme Corp. Antiviral phosphodiamide prodrugs of tenofovir
CN106866737B (en) * 2015-12-11 2020-11-20 南京圣和药物研发有限公司 Phosphonic acid derivatives and their use
WO2017106069A1 (en) 2015-12-15 2017-06-22 Merck Sharp & Dohme Corp. Antiviral oxime phosphoramide compounds
WO2017118928A1 (en) 2016-01-06 2017-07-13 Lupin Limited Process for the separation of diastereomers of tenofovir alafenamide
WO2017134089A1 (en) 2016-02-02 2017-08-10 Sandoz Ag Crystalline forms of tenofovir alafenamide monofumarate
WO2017133517A1 (en) * 2016-02-03 2017-08-10 四川海思科制药有限公司 Phosphamide derivative, method for manufacturing the same, and uses thereof
CN108350007B (en) * 2016-03-01 2020-04-10 深圳市塔吉瑞生物医药有限公司 Substituted adenine compound and pharmaceutical composition thereof
CN107179355B (en) * 2016-03-11 2021-08-10 广东东阳光药业有限公司 Method for separating and detecting tenofovir alafenamide and related substances thereof
CZ2016156A3 (en) 2016-03-17 2017-09-27 Zentiva, K.S. The method of preparation of diastereomerically pure Tenofovir Alafenamide or its salts
CN107226826A (en) * 2016-03-25 2017-10-03 江苏奥赛康药业股份有限公司 Tenofovir Chinese mugwort draws phenol amine fumarate compound and its pharmaceutical composition
WO2017211325A1 (en) 2016-06-05 2017-12-14 上海诚妙医药科技有限公司 New crystal form of tenofovir alafenamide salt, preparation method and use thereof
CN107698621A (en) * 2016-06-20 2018-02-16 杭州和泽医药科技有限公司 A kind of phosphonate prodrugs of adenine derivative and its application in medicine
WO2017221189A1 (en) * 2016-06-22 2017-12-28 Laurus Labs Limited An improved process for the preparation of tenofovir alafenamide or pharmaceutically acceptable salts thereof
CN106317116A (en) * 2016-08-19 2017-01-11 张红利 Phosphamide nucleosides compound, pharmaceutically acceptable salt and application thereof, and pharmaceutical composition
US10449208B2 (en) 2016-08-25 2019-10-22 Merck Sharp & Dohme Corp. Antiviral prodrugs of tenofovir
CN106380484A (en) * 2016-08-29 2017-02-08 杭州百诚医药科技股份有限公司 New crystal form of tenofovir alafenamide and preparation method thereof
WO2018042331A1 (en) 2016-08-31 2018-03-08 Glaxosmithkline Intellectual Property (No.2) Limited Combinations and uses and treatments thereof
WO2018051250A1 (en) 2016-09-14 2018-03-22 Viiv Healthcare Company Combination comprising tenofovir alafenamide, bictegravir and 3tc
US10736908B2 (en) 2016-10-26 2020-08-11 Merck Sharp & Dohme Corp. Antiviral aryl-amide phosphodiamide compounds
CN106565785B (en) * 2016-11-09 2019-11-12 周雨恬 One kind having the active nucleoside phosphoramidate class compound of Anti-HBV activity/HIV and its salt and purposes
CN108129514A (en) * 2016-12-01 2018-06-08 北京美倍他药物研究有限公司 The individual isomer and its medical usage of phosphoric acid/phosphonate derivative
CA3046029A1 (en) * 2016-12-22 2018-06-28 Merck Sharp & Dohme Corp. Antiviral benzyl-amine phosphodiamide compounds
JP6938637B2 (en) 2016-12-22 2021-09-22 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． Tenofovir antiviral aliphatic ester prodrug
WO2018115046A1 (en) 2016-12-23 2018-06-28 Sandoz Ag Crystalline solid forms of tenofovir alafenamide
TWI820984B (en) 2017-01-31 2023-11-01 美商基利科學股份有限公司 Crystalline forms of tenofovir alafenamide
WO2018153977A1 (en) 2017-02-24 2018-08-30 Hexal Ag Stable composition of tenofovir alafenamide
US20190374557A1 (en) * 2017-02-28 2019-12-12 Alexandre Vasilievich Ivachtchenko Cyclobutyl (S)-2-[[[(R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]-propanoates, and production process and application thereof
RU2659388C1 (en) 2017-02-28 2018-07-02 Васильевич Иващенко Александр Nucleotides including n-[(s)-1-cyclobutoxycarbonyl]phosphoramidate fragment, their analogs and their application
CN106866739B (en) * 2017-03-10 2018-11-02 华东师范大学 The preparation method of one kind (R) -1- (6- amino -9H- purine -9- bases) 2- phenyl esters
CA3056072C (en) 2017-03-14 2022-08-23 Gilead Sciences, Inc. Methods of treating feline coronavirus infections
EP3600332B1 (en) 2017-03-20 2023-12-13 The United States of America, as represented by the Secretary, Department of Health and Human Services Hiv post-exposure prophylaxis
CN108794530A (en) * 2017-04-26 2018-11-13 上海医药工业研究院 A kind of the third phenol of tenofovir amidic-salt crystal form and its preparation method and application
CA3059777C (en) 2017-05-01 2023-02-21 Gilead Sciences, Inc. Crystalline forms of (s)-2-ethylbutyl 2-(((s)-(((2r,3s,4r,5r)-5-(4-aminopyrrolo[2,1-f] [1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy) phosphoryl)amino)propanoate
KR102379965B1 (en) * 2017-05-19 2022-03-29 주식회사 종근당 Efficient preparation method of Tenofovir
CN107266499B (en) * 2017-06-05 2019-07-02 珠海优润医药科技有限公司 A kind of antiviral compound and preparation method thereof
CN111587107B (en) 2017-06-30 2023-03-31 希普拉有限公司 Pharmaceutical composition
US10675296B2 (en) 2017-07-11 2020-06-09 Gilead Sciences, Inc. Compositions comprising an RNA polymerase inhibitor and cyclodextrin for treating viral infections
WO2019021319A1 (en) 2017-07-27 2019-01-31 Cipla Limited Pharmaceutical compositions
EP3661937B1 (en) 2017-08-01 2021-07-28 Gilead Sciences, Inc. Crystalline forms of ethyl ((s)-((((2r,5r)-5-(6-amino-9h-purin-9-yl)-4-fluoro-2,5-dihydrofuran-2-yl)oxy)methyl)(phenoxy)phosphoryl)-l-alaninate (gs-9131) for treating viral infections
AR112412A1 (en) 2017-08-17 2019-10-23 Gilead Sciences Inc CHOLINE SALT FORMS OF AN HIV CAPSID INHIBITOR
CN107655987B (en) * 2017-09-08 2020-11-03 厦门蔚扬药业有限公司 HPLC detection method for tenofovir alafenamide and isomer thereof
CN107522743A (en) * 2017-09-30 2017-12-29 深圳科兴生物工程有限公司 A kind of half fumaric acid tenofovir Chinese mugwort draws phenol amine industrial continuous producing method
WO2019084020A1 (en) 2017-10-24 2019-05-02 Gilead Sciences, Inc. Methods of treating patients co-infected with a virus and tuberculosis
CN109942633B (en) * 2017-12-20 2021-08-31 上海新礼泰药业有限公司 Preparation method of tenofovir alafenamide intermediate
CN109942632B (en) * 2017-12-20 2021-08-31 上海博志研新药物研究有限公司 Preparation method of tenofovir alafenamide intermediate
US20200407382A1 (en) 2017-12-30 2020-12-31 Cipla Limited Polymorphic forms of (9-[(r)-2-[[(s)-[[(s)-1-(isopropoxycarbonyl)ethyl]amino]phenoxy phosphinyl]methoxy]propyl] adenine and pharmaceutically acceptable salts thereof
MX2020007393A (en) * 2018-01-10 2020-11-24 Nucorion Pharmaceuticals Inc Phosphor(n)amidatacetal and phosph(on)atalcetal compounds.
EP3737359A4 (en) * 2018-01-12 2021-11-03 Board of Regents of the University of Nebraska Antiviral prodrugs and formulations thereof
PL3752495T3 (en) 2018-02-15 2024-01-15 Gilead Sciences, Inc. Pyridine derivatives and their use for treating hiv infection
CA3175557A1 (en) 2018-02-16 2019-08-22 Gilead Sciences, Inc. Methods and intermediates for preparing a therapeutic compound useful in the treatment of retroviridae viral infection
CN108101943B (en) * 2018-02-28 2020-11-24 顾世海 Tenofovir prodrug or pharmaceutically acceptable salt and application thereof in medicine
WO2019199756A1 (en) 2018-04-09 2019-10-17 Board Of Regents Of The University Of Nebraska Antiviral prodrugs and formulations thereof
EP3823621A1 (en) 2018-07-16 2021-05-26 Gilead Sciences, Inc. Capsid inhibitors for the treatment of hiv
WO2020018399A1 (en) 2018-07-19 2020-01-23 Merck Sharp & Dohme Corp. Phosphinic amide prodrugs of tenofovir
KR20210060573A (en) 2018-09-19 2021-05-26 길리애드 사이언시즈, 인코포레이티드 Integrase inhibitor for HIV prevention
WO2021011891A1 (en) 2019-07-18 2021-01-21 Gilead Sciences, Inc. Long-acting formulations of tenofovir alafenamide
US20220265689A1 (en) 2019-07-19 2022-08-25 THE UNITED STATES OF AMERICA , as represented by the Secretary, Department of Health and Human Hiv pre-exposure prophylaxis
US20220296619A1 (en) 2019-08-19 2022-09-22 Gilead Sciences, Inc. Pharmaceutical formulations of tenofovir alafenamide
EP4017499A4 (en) * 2019-08-22 2024-01-10 Univ Emory Nucleoside prodrugs and uses related thereto
KR20230013013A (en) * 2019-09-20 2023-01-26 애보트 라피드 다이어그노스틱스 인터내셔널 언리미티드 컴퍼니 Antibodies directed against tenofovir and its derivatives
CN114727999A (en) 2019-11-26 2022-07-08 吉利德科学公司 Capsid inhibitors for the prevention of HIV
TWI789695B (en) 2020-01-27 2023-01-11 美商基利科學股份有限公司 Methods for treating sars cov-2 infections
EP4085062A1 (en) 2020-02-20 2022-11-09 Cipla Limited Novel salts and/or co-crystals of tenofovir alafenamide
US11613553B2 (en) 2020-03-12 2023-03-28 Gilead Sciences, Inc. Methods of preparing 1′-cyano nucleosides
CA3169348A1 (en) 2020-03-20 2021-09-23 Gilead Sciences, Inc. Prodrugs of 4'-c-substituted-2-halo-2'-deoxyadenosine nucleosides and methods of making and using the same
WO2021202669A2 (en) 2020-04-01 2021-10-07 Reyoung Corporation Nucleoside and nucleotide conjugate compounds and uses thereof
WO2021207049A1 (en) 2020-04-06 2021-10-14 Gilead Sciences, Inc. Inhalation formulations of 1'-cyano substituted carbanucleoside analogs
KR20210125298A (en) 2020-04-08 2021-10-18 주식회사 파마코스텍 New process for the preparation of Tenofovir alafenamide hemi-tartrate
JP2023523415A (en) 2020-04-21 2023-06-05 リガンド・ファーマシューティカルズ・インコーポレイテッド Nucleotide prodrug compounds
KR20230018473A (en) 2020-05-29 2023-02-07 길리애드 사이언시즈, 인코포레이티드 How to treat remdesivir
EP4172160A2 (en) 2020-06-24 2023-05-03 Gilead Sciences, Inc. 1'-cyano nucleoside analogs and uses thereof
CN115996925A (en) 2020-06-25 2023-04-21 吉利德科学公司 Capsid inhibitors for the treatment of HIV
CN113970612B (en) * 2020-07-22 2023-08-01 北京四环制药有限公司 Method for measuring related substances of propiophenone tenofovir by high performance liquid chromatography
PE20231983A1 (en) 2020-08-27 2023-12-12 Gilead Sciences Inc COMPOUNDS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS
CN112336695B (en) * 2020-09-28 2023-01-03 华北制药华坤河北生物技术有限公司 Propofol fumarate and tenofovir tablet, preparation method thereof and detection method of related substances
WO2022103758A1 (en) 2020-11-11 2022-05-19 Gilead Sciences, Inc. METHODS OF IDENTIFYING HIV PATIENTS SENSITIVE TO THERAPY WITH gp120 CD4 BINDING SITE-DIRECTED ANTIBODIES
US11667656B2 (en) 2021-01-27 2023-06-06 Apotex Inc. Crystalline forms of Tenofovir alafenamide
CN113214322B (en) * 2021-04-30 2022-10-25 山东立新制药有限公司 Green and environment-friendly preparation method of tenofovir
WO2022251594A1 (en) * 2021-05-27 2022-12-01 Antios Therapeutics, Inc. Pharmacokinetics and dose-related improvments in subjects treated with phosphoramidate clevudine prodrugs
TW202342448A (en) 2021-12-03 2023-11-01 美商基利科學股份有限公司 Therapeutic compounds for hiv virus infection
TW202342447A (en) 2021-12-03 2023-11-01 美商基利科學股份有限公司 Therapeutic compounds for hiv virus infection
WO2023102239A1 (en) 2021-12-03 2023-06-08 Gilead Sciences, Inc. Therapeutic compounds for hiv virus infection
CN114369120A (en) * 2022-01-28 2022-04-19 石家庄龙泽制药股份有限公司 Preparation method of key intermediate of prophenoltenofovir
TW202400185A (en) 2022-03-02 2024-01-01 美商基利科學股份有限公司 Compounds and methods for treatment of viral infections
TW202400165A (en) 2022-04-06 2024-01-01 美商基利科學股份有限公司 Bridged tricyclic carbamoylpyridone compounds and uses thereof
TW202402280A (en) 2022-07-01 2024-01-16 美商基利科學股份有限公司 Therapeutic compounds useful for the prophylactic or therapeutic treatment of an hiv virus infection
WO2024044477A1 (en) 2022-08-26 2024-02-29 Gilead Sciences, Inc. Dosing and scheduling regimen for broadly neutralizing antibodies

Family Cites Families (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CS233665B1 (en) 1983-01-06 1985-03-14 Antonin Holy Processing of isomere o-phosphonylmethylderivative of anantiomere racemic vicinal diene
CS263952B1 (en) 1985-04-25 1989-05-12 Holy Antonin Remedy with antiviral effect
CS263951B1 (en) 1985-04-25 1989-05-12 Antonin Holy 9-(phosponylmethoxyalkyl)adenines and method of their preparation
CS264222B1 (en) 1986-07-18 1989-06-13 Holy Antonin N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them
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
US5057301A (en) 1988-04-06 1991-10-15 Neorx Corporation Modified cellular substrates used as linkers for increased cell retention of diagnostic and therapeutic agents
US5053215A (en) * 1988-05-26 1991-10-01 University Of Florida NMR-assayable ligand-labelled trifluorothymidine containing composition and method for diagnosis of HSV infection
US5744600A (en) 1988-11-14 1998-04-28 Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic Phosphonomethoxy carbocyclic nucleosides and nucleotides
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
JP2648516B2 (en) 1989-07-27 1997-09-03 ダイセル化学工業株式会社 Separation of stereoisomers
US5624898A (en) * 1989-12-05 1997-04-29 Ramsey Foundation Method for administering neurologic agents to the brain
JP2925753B2 (en) 1990-02-23 1999-07-28 ダイセル化学工業株式会社 Optical isomer separation method
ATE124050T1 (en) * 1990-04-20 1995-07-15 Acad Of Science Czech Republic CHIRAL 2-(PHOSPHONOMETHOXY)PROPYL-GUANINE AS ANTIVIRAL AGENTS.
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
CZ285420B6 (en) 1990-04-24 1999-08-11 Ústav Organické Chemie A Biochemie Avčr N-(3-fluoro-2-phosphonylmethoxypropyl) derivatives of purine and pyrimidine heterocyclic bases, processes of their preparation and use
US5627165A (en) * 1990-06-13 1997-05-06 Drug Innovation & Design, Inc. Phosphorous prodrugs and therapeutic delivery systems using same
US5177064A (en) 1990-07-13 1993-01-05 University Of Florida Targeted drug delivery via phosphonate derivatives
CS276072B6 (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
JP3116079B2 (en) 1990-08-10 2000-12-11 インスティチュート オブ オーガニック ケミストリ アンド バイオケミストリ アカデミー オブ サイエンス オブ ザ チェコ リパブリック Novel nucleotide production method
DE10399025I2 (en) 1990-09-14 2007-11-08 Acad Of Science Czech Republic Active substance precursors of phosphonates
US5827819A (en) * 1990-11-01 1998-10-27 Oregon Health Sciences University Covalent polar lipid conjugates with neurologically active compounds for targeting
US5208221A (en) 1990-11-29 1993-05-04 Bristol-Myers Squibb Company Antiviral (phosphonomethoxy) methoxy purine/pyrimidine derivatives
CZ284678B6 (en) 1991-05-20 1999-01-13 Ústav Organické Chemie A Biochemie Avčr Di(2-propyl)esters of 1-fluoro-2-phosphonomethoxy-3-p-toluenesulfonyloxypropanes, process of their preparation and use
US5498752A (en) 1991-08-22 1996-03-12 Daicel Chemical Industries, Ltd. Process for recovering optical isomers and solvent, process for using solvent by circulation and process for reusing optical isomers in optical resolution
JP3010816B2 (en) 1991-08-22 2000-02-21 ダイセル化学工業株式会社 Method for recovering optical isomer and solvent in optical resolution, method for recycling solvent, and method for reusing optical isomer
JP3497505B2 (en) 1991-10-11 2004-02-16 インスティテュート オブ オルガニック ケミストリー アンド バイオケミストリー オブ ザ アカデミー オブ サイエンシズ オブ ザ チェコ パブリック Antiviral acyclic phosphonomethoxyalkyl-substituted alkenyl and alkynylpurine and pyrimidine derivatives
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
IL106998A0 (en) * 1992-09-17 1993-12-28 Univ Florida Brain-enhanced delivery of neuroactive peptides by sequential metabolism
US6413949B1 (en) * 1995-06-07 2002-07-02 D-Pharm, Ltd. Prodrugs with enhanced penetration into cells
US5656745A (en) * 1993-09-17 1997-08-12 Gilead Sciences, Inc. Nucleotide analogs
EP0719274A1 (en) * 1993-09-17 1996-07-03 Gilead Sciences, Inc. Method for dosing therapeutic compounds
US5798340A (en) * 1993-09-17 1998-08-25 Gilead Sciences, Inc. Nucleotide analogs
DE69435319D1 (en) 1993-09-17 2010-12-16 Gilead Sciences Inc nucleotide analogs
GB9505025D0 (en) 1995-03-13 1995-05-03 Medical Res Council Chemical compounds
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
PT828749E (en) * 1995-05-26 2003-11-28 Genta Inc COMPOSITIONS AND METHODS FOR SYNTHESIS OF ORGANOPHOSPHORUS DERIVATIVES
NZ325704A (en) 1995-12-29 2000-02-28 Gilead Sciences Inc Nucleotide analogs
US5717095A (en) * 1995-12-29 1998-02-10 Gilead Sciences, Inc. Nucleotide analogs
US5874577A (en) * 1996-04-03 1999-02-23 Medichem Research, Inc. Method for the preparing 9-12-(Diethoxyphosphonomethoxy)ethyl!adenine and analogues thereof
US5922695A (en) * 1996-07-26 1999-07-13 Gilead Sciences, Inc. Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability
JP4033494B2 (en) * 1996-07-26 2008-01-16 ギリヤド サイエンシーズ， インコーポレイテッド Nucleotide analogs
US5739314A (en) 1997-04-25 1998-04-14 Hybridon, Inc. Method for synthesizing 2'-O-substituted pyrimidine nucleosides
EP0996430B1 (en) 1997-07-25 2002-11-27 Gilead Sciences, Inc. Nucleotide analog compositions
US5935946A (en) 1997-07-25 1999-08-10 Gilead Sciences, Inc. Nucleotide analog composition and synthesis method
NZ501287A (en) 1997-07-25 2001-09-28 Gilead Sciences Inc Nucleotide analog composition and synthesis method comprising 9-(2-hydroxypropyl)adenine and lithium alkoxide in a cystalline form.
WO1999030727A1 (en) * 1997-12-17 1999-06-24 Enzon, Inc. Polymeric prodrugs of amino- and hydroxyl-containing bioactive agents
EP1045897B1 (en) * 1998-01-23 2002-01-30 Newbiotics Inc. Enzyme catalyzed therapeutic agents
US6169078B1 (en) * 1998-05-12 2001-01-02 University Of Florida Materials and methods for the intracellular delivery of substances
AU755564B2 (en) * 1998-06-20 2002-12-12 Washington University Membrane-permeant peptide complexes for medical imaging, diagnostics, and pharmaceutical therapy
US6169879B1 (en) * 1998-09-16 2001-01-02 Webtv Networks, Inc. System and method of interconnecting and using components of home entertainment system
GB9821058D0 (en) † 1998-09-28 1998-11-18 Univ Cardiff Chemical compound
TWI230618B (en) * 1998-12-15 2005-04-11 Gilead Sciences Inc Pharmaceutical compositions of 9-[2-[[bis[(pivaloyloxy)methyl]phosphono]methoxy]ethyl]adenine and tablets or capsules containing the same
US7115590B1 (en) † 1999-02-12 2006-10-03 University College Cardiff Consultants Limited Phosphoramidate, and mono-, di-, and tri-phosphate esters of (1R, cis)-4-(6-amino-9H-purin-9-yl)-2-cyclopentene-1-methanol as antiviral agents
EP1301519B2 (en) * 2000-07-21 2021-11-10 Gilead Sciences, Inc. Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same
AU2002220979A1 (en) * 2000-10-13 2002-04-22 Xigen Sa Intracellular delivery of biological effectors by novel transporter peptide sequences
US20020119433A1 (en) * 2000-12-15 2002-08-29 Callender Thomas J. Process and system for creating and administering interview or test

Also Published As

Publication number Publication date
US20050124585A1 (en) 2005-06-09
NO336718B1 (en) 2015-10-26
LTC1301519I2 (en) 2023-02-27
FR16C0013I2 (en) 2016-09-09
ZA200210271B (en) 2003-12-31
DK1301519T3 (en) 2015-05-26
NO20120466L (en) 2003-03-20
US7803788B2 (en) 2010-09-28
JP2011140506A (en) 2011-07-21
NO2016006I1 (en) 2016-04-19
EE05366B1 (en) 2010-12-15
US20020119443A1 (en) 2002-08-29
HK1054238A1 (en) 2003-11-21
NZ523438A (en) 2005-02-25
WO2002008241A2 (en) 2002-01-31
ES2536972T3 (en) 2015-06-01
LTPA2016009I1 (en) 2016-04-25
NO20030270D0 (en) 2003-01-20
OA12393A (en) 2006-04-18
CZ304734B6 (en) 2014-09-10
CN100402539C (en) 2008-07-16
NL300803I2 (en) 2016-06-30
US7390791B2 (en) 2008-06-24
CA2416757C (en) 2011-02-15
CN1706855A (en) 2005-12-14
PT1301519E (en) 2015-06-11
US20050159392A1 (en) 2005-07-21
JP2010174033A (en) 2010-08-12
HU230960B1 (en) 2019-06-28
BR0112646A (en) 2003-06-24
EP1301519A2 (en) 2003-04-16
BRPI0112646B1 (en) 2017-10-17
AP2003002724A0 (en) 2003-06-30
CZ2003413A3 (en) 2003-12-17
EP2682397A1 (en) 2014-01-08
CY2016008I1 (en) 2016-12-14
EP3235823A1 (en) 2017-10-25
AP1466A (en) 2005-09-22
NO20131717L (en) 2003-03-20
JP5063554B2 (en) 2012-10-31
CZ304886B6 (en) 2015-01-07
IS6689A (en) 2003-01-17
LU93029I2 (en) 2016-06-14
EA200300188A1 (en) 2003-06-26
NZ535408A (en) 2006-09-29
AU2005225039B2 (en) 2008-09-25
TR200300055T2 (en) 2004-12-21
NZ536942A (en) 2006-03-31
IS2985B (en) 2017-09-15
HUS000494I2 (en) 2021-03-29
AU2001282941C1 (en) 2016-12-22
CY2016008I2 (en) 2016-12-14
HRP20030047A2 (en) 2007-08-31
AU2005225039A1 (en) 2005-11-10
LT2682397T (en) 2017-06-12
KR20060105807A (en) 2006-10-11
ES2627903T3 (en) 2017-08-01
NO20150909L (en) 2003-03-20
PL213214B1 (en) 2013-01-31
JP2004504402A (en) 2004-02-12
SI1301519T1 (en) 2015-07-31
DK2682397T3 (en) 2017-06-19
MXPA03000587A (en) 2004-04-05
AU8294101A (en) 2002-02-05
JP4651264B2 (en) 2011-03-16
FR16C0013I1 (en) 2016-05-27
BG107572A (en) 2003-11-28
BE2016C018I2 (en) 2020-08-20
WO2002008241A3 (en) 2002-08-29
PL360490A1 (en) 2004-09-06
KR100767432B1 (en) 2007-10-17
KR100749160B1 (en) 2007-08-14
EP1301519B2 (en) 2021-11-10
BG66037B1 (en) 2010-11-30
EP1301519B1 (en) 2015-02-25
CN1291994C (en) 2006-12-27
HRP20160074A8 (en) 2016-07-29
HK1243711A1 (en) 2018-07-20
US20080227754A1 (en) 2008-09-18
NO2023006I1 (en) 2023-02-03
AU2001282941B2 (en) 2006-04-27
CA2893174A1 (en) 2002-01-31
US20040018150A1 (en) 2004-01-29
US20050009043A1 (en) 2005-01-13
HUS1900027I1 (en) 2021-03-29
US20030219727A1 (en) 2003-11-27
EA004926B1 (en) 2004-10-28
US20050124584A1 (en) 2005-06-09
ES2536972T5 (en) 2022-04-06
DK1301519T4 (en) 2021-12-20
NO2016006I2 (en) 2016-04-19
HUP0301307A2 (en) 2003-09-29
KR20030022295A (en) 2003-03-15
HRP20030047B1 (en) 2016-02-26
IL153658A0 (en) 2003-07-06
HUP0301307A3 (en) 2005-12-28
US20060024659A1 (en) 2006-02-02
SI2682397T1 (en) 2017-08-31
EP2682397B1 (en) 2017-04-19
JP2009062383A (en) 2009-03-26
BRPI0112646B8 (en) 2021-05-25
CY1119411T1 (en) 2018-03-07
HRP20160074B1 (en) 2021-09-03
UA75889C2 (en) 2006-06-15
EE200300029A (en) 2004-10-15
HRP20160074A2 (en) 2016-03-11
JP5111551B2 (en) 2013-01-09
US20050124583A1 (en) 2005-06-09
CA2725819A1 (en) 2002-01-31
NO20030270L (en) 2003-03-20
CA2725819C (en) 2015-09-22
CN1443189A (en) 2003-09-17
PT2682397T (en) 2017-05-31

Similar Documents

Publication Publication Date Title
CA2416757A1 (en) Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same
US11559542B2 (en) Phosphoramidate derivatives of 5-fluoro-2′-deoxyuridine for use in the treatment of cancer
ES2242965T3 (en) DERIVATIVES OF ARIL-ESTER PHOSPHORAMIDATE OF 2 ', 3'-DIDEHYDRONUCLEOSIDS.
US8569478B2 (en) Modified 4′-nucleosides as antiviral agents
ES2924225T3 (en) Amino-methylpiperidine derivative as a kinase inhibitor
US8551965B2 (en) Anti-viral pyrimidine nucleoside analogues
JP5864590B2 (en) Amidophosphite derivatives of gemcitabine for use in cancer treatment
ES2922633T3 (en) Oxy-fluoropiperidine derivative as a kinase inhibitor
US5854228A (en) Antiviral phosphonomethoxyalkylene purine and pyrimidine derivatives
JP2017535587A (en) Novel 2 'and / or 5' amino acid ester phosphoramidate 3'-deoxyadenosine derivatives as anticancer compounds
JP2007523180A (en) Nucleoside phosphonate derivatives useful for the treatment of HIV infection
EP0630381B1 (en) Antiviral acyclic phosphonomethoxyalkyl substituted, alkenyl and alkynyl purine and pyrimidine derivatives
EP0437469A1 (en) Nucleoside derivatives
Kim et al. Synthesis of 9‐[(2‐hydroxy‐1‐phosphonylethoxy) ethyl] guanine, 1‐[(2‐hydroxy‐1‐phosphonylethoxy) ethyl] cytosine and 9‐[(2‐hydroxy‐1‐phosphonylethoxy) ethyl] adenine
AR011965A1 (en) EPOXY-AZETIDINONE COMPOUNDS, A PROCEDURE FOR THE PREPARATION AND USE OF SUCH COMPOUNDS AS INTERMEDIATES FOR THE PREPARATION OF NEW ANALOGS FROM OXAPENAM
AR033606A1 (en) USE OF DINUCLEOSIDE POLYPHOSPHATE FOR THE MANUFACTURE OF A MEDICINAL PRODUCT TO STIMULATE THE ELIMINATION OF FLUID IN THE RELEASE OF RETINA AND THE RETINA EDEMA AND SUCH COMPOUNDS.

Legal Events

Date Code Title Description
EEER Examination request
MKEX Expiry

Effective date: 20210720