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Synthesis and antiviral activity of monofluoro and difluoro analogs of pyrimidine deoxyribonucleosides against human immunodeficiency virus (HIV-1)
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1990
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Bioorganic ChemistryAntiviral DrugHuman Immunodeficiency VirusChemical BiologyPharmaceutical ChemistryMedicinal ChemistryAntiviral ActivityAntiviral Drug DevelopmentDifluoro AnalogsBiochemistryStructure-activity RelationshipsHivPharmacologyAntiviral CompoundBiomolecular EngineeringNatural SciencesAntiviral TherapyPyrimidine DeoxyribonucleosidesMedicineDrug Discovery
A range of 2'-fluoro and 2',3'-difluoro analogues of pyrimidine deoxyribonucleosides have been synthesized and evaluated against human immunodeficiency virus (HIV-1) in a human lymphoblastoid cell line. Among these compounds, 1-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)cytosine (12), 2',3'-didehydro-2',3'-dideoxy-2'-fluorocytidine (35), 1-(2,3-dideoxy-2,3-difluoro-beta-D-arabinofuranosyl)cytosine (41), and 3'-deoxy-2',3'-didehydro-2'-fluorothymidine (45) were found to have significant antiviral activity, with IC50 values of 0.65, 10, 10, and 100 microM, respectively. The structure-activity relationships are discussed.