722539-41-5Relevant academic research and scientific papers
Second Generation of cycloSal-Pronucleotides with Esterase-Cleavable Sites: The "Lock-In"-Concept
Meier, Chris,Ruppel, Manuel F. H.,Vukadinovic, Dalibor,Balzarini, Jan
, p. 89 - 115 (2007/10/03)
A conceptual extension of the cycloSal-pronucleotide approach is presented. The characteristic feature of the new cycloSal-derivatives of the anti-HIV active nucleoside analogue d4T 1 is the incorporation of an enzymatically cleavable carboxylic ester moiety with the intention to trap the triesters inside cells ("lock-in"-concept). CycloSal-triesters bearing different ester groups in the 3-or 5-position of the cycloSal-moiety are described. Surprisingly, only acetyl-and levulinyl esters are cleaved readily in CEM cell extracts while alkyl esters were found to be stable. Nevertheless, in in-vitro anti-HIV assays most of the compounds achieve the thymidine-kinase bypass, thus proving that they act at least as nucleotide delivery systems.
