Počet záznamů: 1

Phosphoramidate pronucleotides of cytostatic 6-aryl-7-deazapurine ribonucleosides

  1. 1.
    0360990 - UOCHB-X 2012 RIV GB eng J - Článek v odborném periodiku
    Perlíková, Pavla - Pohl, Radek - Votruba, Ivan - Shih, R. - Birkuš, G. - Cihlář, T. - Hocek, Michal
    Phosphoramidate pronucleotides of cytostatic 6-aryl-7-deazapurine ribonucleosides.
    Bioorganic & Medicinal Chemistry. Roč. 19, č. 1 (2011), s. 229-242 ISSN 0968-0896
    Grant CEP: GA MŠk 1M0508; GA ČR GAP207/11/0344
    Výzkumný záměr: CEZ:AV0Z40550506
    Klíčová slova: nucleosides * prodrugs * proTides * phosphoramidates * pyrrolo[2,3-d]pyrimidines
    Kód oboru RIV: CC - Organická chemie
    Impakt faktor: 2.921, rok: 2011

    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. However, active efflux of prodrugs may play a role in their weak cytotoxic activity.
    Trvalý link: http://hdl.handle.net/11104/0198414