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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F11%3A00360990" target="_blank" >RIV/61388963:_____/11:00360990 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.bmc.2010.11.029" target="_blank" >http://dx.doi.org/10.1016/j.bmc.2010.11.029</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2010.11.029" target="_blank" >10.1016/j.bmc.2010.11.029</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CC - Organická chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2011

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Bioorganic & Medicinal Chemistry

ISSN

0968-0896

e-ISSN

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Svazek periodika

19

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

229-242

Kód UT WoS článku

000285724800022

EID výsledku v databázi Scopus

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