Inhibition of human thymidine phosphorylase by conformationally constrained pyrimidine nucleoside phosphonic acids and their "open-structure" isosteres

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F14%3A00428628" target="_blank" >RIV/61388963:_____/14:00428628 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.ejmech.2013.12.026" target="_blank" >http://dx.doi.org/10.1016/j.ejmech.2013.12.026</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2013.12.026" target="_blank" >10.1016/j.ejmech.2013.12.026</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Inhibition of human thymidine phosphorylase by conformationally constrained pyrimidine nucleoside phosphonic acids and their "open-structure" isosteres

Popis výsledku v původním jazyce

A series of conformationally constrained uridine-based nucleoside phosphonic acids containing annealed 1,3-dioxolane and 1,4-dioxane rings and their "open-structure" isosteres were synthesized and evaluated as potential multisubstrate-like inhibitors ofthe human recombinant thymidine phosphorylase (TP, EC 2.4.2.4) and TP obtained from peripheral blood mononuclear cells (PBMC). From a large set of tested nucleoside phosphonic acids, several potent compounds were identified that exhibited K-i values in the range of 0.048-1 mu M. The inhibition potency of the studied compounds strongly depended on the degree of conformational flexibility of the phosphonate moiety, the stereochemical arrangement of the sugarphosphonate component, and the substituent at position 5 of the pyrimidine nucleobase.

Název v anglickém jazyce

Inhibition of human thymidine phosphorylase by conformationally constrained pyrimidine nucleoside phosphonic acids and their "open-structure" isosteres

Popis výsledku anglicky

A series of conformationally constrained uridine-based nucleoside phosphonic acids containing annealed 1,3-dioxolane and 1,4-dioxane rings and their "open-structure" isosteres were synthesized and evaluated as potential multisubstrate-like inhibitors ofthe human recombinant thymidine phosphorylase (TP, EC 2.4.2.4) and TP obtained from peripheral blood mononuclear cells (PBMC). From a large set of tested nucleoside phosphonic acids, several potent compounds were identified that exhibited K-i values in the range of 0.048-1 mu M. The inhibition potency of the studied compounds strongly depended on the degree of conformational flexibility of the phosphonate moiety, the stereochemical arrangement of the sugarphosphonate component, and the substituent at position 5 of the pyrimidine nucleobase.

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

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

Název periodika

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

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Svazek periodika

74

Číslo periodika v rámci svazku

Mar 3

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

24

Strana od-do

145-168

Kód UT WoS článku

000333780800015

EID výsledku v databázi Scopus

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