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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| creator | Becker Mark W Kernan Michael R Lee William A Sparacino Mark L He Gong-Xin Rohloff John C Cihlar Tomas Prisbe Ernest J Chapman Harlan H Eisenberg Eugene J |
| 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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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. 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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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