Synthesis and biological activities of 4-O-(difluoromethyl)-5-substituted-uracil nucleoside analogs

Various 4-O-difluoromethyl analogues of 5-substituted uridine (Urd), 2'-deoxyuridine (dUrd), and arabinofuranosyluracil (araU) nucleosides were prepared via a CF2-insertion reaction into 4-O-silylated nucleosides and evaluated for activity against herpes simplex virus type 1 (HSV-1) and type 2...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 1988-02, Vol.31 (2), p.393-397
Main Authors: Reefschlaeger, Juergen, Pein, Claus Dietmar, Cech, Dieter
Format: Article
Language:English
Subjects:
Antiviral Agents - chemical synthesis
Antiviral Agents - pharmacology
Antiviral Agents - toxicity
Arabinofuranosyluracil - analogs & derivatives
Arabinofuranosyluracil - pharmacology
Carbohydrates. Nucleosides and nucleotides
Chemistry
Deoxyuridine - analogs & derivatives
Deoxyuridine - pharmacology
Exact sciences and technology
Humans
Nucleosides, nucleotides and oligonucleotides
Organic chemistry
Preparations and properties
Simplexvirus - drug effects
Structure-Activity Relationship
Uridine - analogs & derivatives
Uridine - pharmacology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Various 4-O-difluoromethyl analogues of 5-substituted uridine (Urd), 2'-deoxyuridine (dUrd), and arabinofuranosyluracil (araU) nucleosides were prepared via a CF2-insertion reaction into 4-O-silylated nucleosides and evaluated for activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and cytotoxicity in human embryonic lung fibroblast (HELF) cell cultures. The introduction of the 4-substituent led to a strong reduction of antiviral activity for dUrd but not for araU analogues. Three of the 4,5-disubstituted uracil nucleoside derivatives, 4-O-(difluoromethyl)-5-bromo-araU (5c),-5-methyl-araU (5e), and -(E)-5-(2-bromovinyl)-araU (5g), displayed a high and selective inhibitory effect against HSV-1, but only 5e was effective against both HSV-1 and HSV-2 comparably with the antiherpes potential of the reference compounds 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir) and 1-beta-D-arabino-furanosylthymine (araT).
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00397a022