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

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...

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Hauptverfasser: He, Gong-Xin, Eisenberg, Eugene, J, Becker, Mark, W, Kernan, Michael, R, Sparacino, Mark, L, Cihlar, Tomas, Lee, William, A, Prisbe, Ernest, J, Rohloff, John, C, Chapman, Harlan, H
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creator He, Gong-Xin
Eisenberg, Eugene, J
Becker, Mark, W
Kernan, Michael, R
Sparacino, Mark, L
Cihlar, Tomas
Lee, William, A
Prisbe, Ernest, J
Rohloff, John, C
Chapman, Harlan, H
description 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.
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subjects ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM
BEER
BIOCHEMISTRY
CHEMISTRY
COMPOSITIONS OR TEST PAPERS THEREFOR
CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES
DERIVATIVES THEREOF
ENZYMOLOGY
HUMAN NECESSITIES
HYGIENE
INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES
MEASURING
MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS
MEDICAL OR VETERINARY SCIENCE
METALLURGY
MICROBIOLOGY
MUTATION OR GENETIC ENGINEERING
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC CHEMISTRY
PHYSICS
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
PROCESSES OF PREPARING SUCH COMPOSITIONS
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS
SPIRITS
SUGARS
TESTING
VINEGAR
WINE
title Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same
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