Phosphoramidate pronucleotides of cytostatic 6-aryl-7-deazapurine ribonucleosides
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21134754
DOI
10.1016/j.bmc.2010.11.029
PII: S0968-0896(10)01042-4
Knihovny.cz E-resources
- MeSH
- Spectrometry, Mass, Electrospray Ionization MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy MeSH
- Cell Line, Tumor MeSH
- Antineoplastic Agents chemistry pharmacology MeSH
- Purine Nucleosides chemistry pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antineoplastic Agents MeSH
- Purine Nucleosides MeSH
A series of O-phenyl methyl-, ethyl- and benzylalanyl phosphoramidate pronucleotides derived from cytostatic 6-aryl-7-deazapurine ribonucleosides were prepared by the cross-coupling reactions of the 2',3'-isopropylidene protected 6-chloro-7-deazapurine ribonucleoside phosphoramidates with (het)arylboronic acids or -stannanes followed by deprotection. Most of the prepared prodrugs exerted in vitro cytostatic effects against both solid tumor and lymphoid cancer cells within low micromolar range of concentrations. These activities were in general weaker or comparable to the activities of the parent nucleosides. Additional testing of selected prodrugs suggests that the lack of activity improvement over parent nucleosides is not due to the lack of permeability or inefficient catabolism of alanyl-ester by intracellular hydrolases. More likely, active efflux of prodrugs may play a role in their weak cytotoxic activity.
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