Novel nucleotide analogues bearing (1H-1,2,3-triazol-4-yl)phosphonic acid moiety as inhibitors of Plasmodium and human 6-oxopurine phosphoribosyltransferases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00474802" target="_blank" >RIV/61388963:_____/17:00474802 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.tet.2016.12.046" target="_blank" >http://dx.doi.org/10.1016/j.tet.2016.12.046</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tet.2016.12.046" target="_blank" >10.1016/j.tet.2016.12.046</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel nucleotide analogues bearing (1H-1,2,3-triazol-4-yl)phosphonic acid moiety as inhibitors of Plasmodium and human 6-oxopurine phosphoribosyltransferases

Popis výsledku v původním jazyce

A novel family of acyclic nucleoside phosphonates (ANPs) bearing a (1H-1,2,3-triazol-4-yl)phosphonic acid group in the acyclic side chain have been prepared in order to study the influence of the hetaryl rigidizing element on the biological properties of such compounds. The key synthetic step consisted of a copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) between diethyl ethynylphosphonate and the corresponding azidoalkyl precursor. Two ANPs in this family, bearing a guanine base, exhibited the highest potency for the human 6-oxopurine phosphoribosyltransferase irrespective of the stereochemistry on the C-2' atom. Four compounds inhibited Plasmodium falciparum 6-oxopurine phosphoribosyltransferase with little differences in their K-i values irrespective of whether the base was guanine, hypoxanthine or xanthine but only two, with guanine as base, inhibited PvHGPRT.

Název v anglickém jazyce

Novel nucleotide analogues bearing (1H-1,2,3-triazol-4-yl)phosphonic acid moiety as inhibitors of Plasmodium and human 6-oxopurine phosphoribosyltransferases

Popis výsledku anglicky

A novel family of acyclic nucleoside phosphonates (ANPs) bearing a (1H-1,2,3-triazol-4-yl)phosphonic acid group in the acyclic side chain have been prepared in order to study the influence of the hetaryl rigidizing element on the biological properties of such compounds. The key synthetic step consisted of a copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) between diethyl ethynylphosphonate and the corresponding azidoalkyl precursor. Two ANPs in this family, bearing a guanine base, exhibited the highest potency for the human 6-oxopurine phosphoribosyltransferase irrespective of the stereochemistry on the C-2' atom. Four compounds inhibited Plasmodium falciparum 6-oxopurine phosphoribosyltransferase with little differences in their K-i values irrespective of whether the base was guanine, hypoxanthine or xanthine but only two, with guanine as base, inhibited PvHGPRT.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GA16-06049S" target="_blank" >GA16-06049S: Inhibitory 6-oxopurin fosforibosyltransferáz založené na acyklických nukleosidfosfonátech: potenciální nové antibakteriální a antiparazitické látky</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Tetrahedron

ISSN

0040-4020

e-ISSN

—

Svazek periodika

73

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

692-702

Kód UT WoS článku

000393003500006

EID výsledku v databázi Scopus

2-s2.0-85008441646