Abstract
The silylated AzddThd 5 and AzddUrd 6 prepared from 2,3'-anhydronucleoside derivatives 3 and 4 were transformed to formamides 7 and 8 by using the sequence RN3----RN = P(C6H5)----RNHCHO. Formamides 7 and 8 were dehydrated to the protected 3'-isocyano derivatives 9 and 10; deblocking gave 11 and 12. Neither 3'-isocyano-3'-deoxythymidine (11) nor 3'-isocyano-2',3'-dideoxyuridine (12) showed anti-HIV activity at noncytotoxic concentrations. ddThd derivative 11 was considerably more toxic to MT-4 cells than ddUrd derivative 12; it also had a much greater affinity (Ki) for MT-4 cell dThd kinase than ddUrd derivative 12. Both compounds appear to be linear mixed-type inhibitors of MT-4 cell dThd kinase.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimetabolites / chemical synthesis
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / metabolism
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Cell Survival / drug effects
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Chemical Phenomena
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Chemistry
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Dideoxynucleosides / chemical synthesis*
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Dideoxynucleosides / metabolism
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Dideoxynucleosides / pharmacology
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HIV / drug effects*
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Kinetics
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Phosphorylation
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Thymidine / analogs & derivatives*
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Thymidine / chemical synthesis
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Thymidine / metabolism
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Thymidine / pharmacology
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Thymidine Kinase / antagonists & inhibitors*
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Virus Replication / drug effects
Substances
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Antimetabolites
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Antiviral Agents
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Dideoxynucleosides
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3'-isocyano-3'-deoxythymidine
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3'-isocyano-2',3'-dideoxyuridine
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Thymidine Kinase
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Thymidine