Abstract
Methylenecyclobutane analogues of 2'-deoxyadenosine, 2'-deoxyguanosine and 2'-deoxycytidine, and the corresponding phosphoralaninate pronucleotides comprising adenine and guanine bases, were synthesized as potential antiviral agents. Phosphoralaninate of adenine methylenecyclobutane was a potent inhibitor of replication of Epstein-Barr virus (EBV) in Daudi cell culture. Phosphoralaninate of guanine analogue was inactive but both pronucleotides were substrates for porcine liver esterase. Adenine methylenecyclobutane analogue was deaminated by adenosine deaminase.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Deaminase / chemistry
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Adenosine Deaminase / metabolism
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Alanine / analogs & derivatives*
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Alanine / pharmacology*
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Animals
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology*
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Cell Line
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Cyclobutanes / chemical synthesis*
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Cyclobutanes / chemistry
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Cyclobutanes / pharmacology*
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Deamination
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Esterases / metabolism
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Fibroblasts / drug effects
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Herpesvirus 4, Human / drug effects*
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Humans
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Lethal Dose 50
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Liver / enzymology
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Nucleosides / chemical synthesis*
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Nucleosides / chemistry
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Nucleosides / pharmacology
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Prodrugs / chemical synthesis
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Prodrugs / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
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Swine
Substances
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Antiviral Agents
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Cyclobutanes
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Nucleosides
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Prodrugs
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Esterases
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Adenosine Deaminase
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Alanine