43135-49-5Relevant articles and documents
Studies on enzyme-cleavable dialkoxymethyl-cycloSaligenyl-2′, 3′-dideoxy-2′,3′-didehydrothymidine monophosphates
Gisch, Nicolas,Balzarini, Jan,Meier, Chris
experimental part, p. 6752 - 6760 (2009/11/30)
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 (RP or SP) was achieved. By X-ray structure analysis, the absolute configuration at the P-atom was assigned. For all separated diastereomers the (SP) form showed better antiviral activity than the (RP) form.
