Abstract
1-(2-Deoxy-beta-D-ribofuranosyl)-5-bromo-2-pyrimidinone (BrPdR) and 1-(2-deoxy-beta-D-ribofuranosyl)-5-iodo-2-pyrimidinone (IPdR) have been synthesized by condensation of the appropriate silylated bases 2a and 2b, respectively, with 3,5-bis-O-(p-chlorobenzoyl)-2-deoxy-alpha-D-ribofuranosyl chloride (8) in 1,2-dichloroethane, in the presence of SnCl4, followed by separation of the anomeric blocked nucleosides via column chromatography and subsequent deprotection with methanolic ammonia. Both BrPdR and IPdR exhibited significant antiherpes activities against various strains of HSV-1 and HSV-2, the latter compound (IPdR) showing the higher activity as well as the stronger binding to the virus-specific thymidine kinase.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Line
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Chemical Phenomena
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Chemistry
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Cytidine Deaminase
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Drug Resistance, Microbial
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Humans
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Magnetic Resonance Spectroscopy
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Nucleoside Deaminases / metabolism
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Pyrimidine Nucleosides / chemical synthesis*
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Pyrimidine Nucleosides / metabolism
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Pyrimidine Nucleosides / pharmacology
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Simplexvirus / drug effects*
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Simplexvirus / enzymology
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Thymidine Kinase / antagonists & inhibitors
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Tin
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Tin Compounds*
Substances
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Pyrimidine Nucleosides
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Tin Compounds
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stannous chloride
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ropidoxuridine
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Tin
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1-(2-deoxy-beta-ribofuranosyl)-5-bromo-2-pyrimidinone
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Thymidine Kinase
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Nucleoside Deaminases
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Cytidine Deaminase
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deoxycytidine deaminase