Stereoselective synthesis and biological evaluation as inhibitors of hepatitis C virus RNA polymerase of GSK3082 analogues with structural diversity at the 5-position.

08:00 EDT 12th March 2019 | BioPortfolio

Summary of "Stereoselective synthesis and biological evaluation as inhibitors of hepatitis C virus RNA polymerase of GSK3082 analogues with structural diversity at the 5-position."

GSK3082 - a hepatitis C virus RNA polymerase inhibitor - and a series of analogues with structural diversity at the 5-position were prepared from a 2,2,4,5-tetrasubstituted pyrrolidine obtained with a well-defined stereochemistry from the 1,3-dipolar cycloaddition of the chiral imino ester derived from leucine tert-butyl ester and (R)-2,3-O-isopropylideneglyceraldehyde with methyl acrylate. The chiral 2,2-dimethyl-1,3-dioxolane moiety provided by the glyceraldehyde served as a synthetic equivalent for different substituents and functional groups and these transformations usually required mild reaction conditions and simple work-up procedures. The inhibitory activity of the resulting GSK3082 analogues was studied in vitro in a cell-based assay of the subgenomic HCV RNA replication system. Some of the analogues showed good inhibitory activity with IC50 values in the nanomolar concentration range.


Journal Details

This article was published in the following journal.

Name: European journal of medicinal chemistry
ISSN: 1768-3254
Pages: 401-419


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