Title: Studies on enzyme-cleavable dialkoxymethyl-cyclosaligenyl-2',3'-dideoxy-2',3'-didehydrothymidine monophosphates
Authors: Gisch, Nicolas ×
Balzarini, Jan
Meier, Chris #
Issue Date: Nov-2008
Publisher: ACS Publications
Series Title: Journal of Medicinal Chemistry vol:51 issue:21 pages:6752-6760
Abstract: Recently we reported on conceptually new enzymatically activated cycloSal-pronucleotides. Now, we developed this concept further with new compounds of this type. The basic idea is fast intracellular cleavage of a functionalized group at the cycloSal residue that results in a rapid delivery of the nucleotide and thus an intracellular enrichment of the nucleotide. The introduction of a higher alkylated acylal group, the di- iso-butyryloxymethyl group, to the aromatic ring led to the expected higher stability of these prodrugs against enzymatic cleavage but also entailed surprisingly a decrease in hydrolysis stabilities and solubility problems. For some compounds, a separation of the two diastereomeric forms ( R P or S P) was achieved. By X-ray structure analysis, the absolute configuration at the P-atom was assigned. For all separated diastereomers the ( S P) form showed better antiviral activity than the ( R P) form.
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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