Purine analogs as phosphatidylinositol 4-kinase III beta inhibitors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00460249" target="_blank" >RIV/61388963:_____/16:00460249 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.bmcl.2016.04.002" target="_blank" >http://dx.doi.org/10.1016/j.bmcl.2016.04.002</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmcl.2016.04.002" target="_blank" >10.1016/j.bmcl.2016.04.002</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Purine analogs as phosphatidylinositol 4-kinase III beta inhibitors

Popis výsledku v původním jazyce

We report on an extensive structure-activity relationship study of novel PI4K III beta inhibitors. The purine derivative of the potent screening hit T-00127-HEV1 has served as a suitable starting point for a thorough investigation of positions 8 and 2. While position 8 of the purine scaffold can only bear a small substituent to maintain the inhibitory activity, position 2 is opened for extensive modification and can accommodate even substituted phenyl rings without the loss of PI4K III beta inhibitory activity. These empirical observations nicely correlate with the results of our docking study, which suggests that position 2 directs towards solution and can provide the necessary space for the interaction with remote residues of the enzyme, whereas the cavity around position 8 is strictly limited. The obtained compounds have also been subjected to antiviral screening against a panel of (+) ssRNA viruses.

Název v anglickém jazyce

Purine analogs as phosphatidylinositol 4-kinase III beta inhibitors

Popis výsledku anglicky

We report on an extensive structure-activity relationship study of novel PI4K III beta inhibitors. The purine derivative of the potent screening hit T-00127-HEV1 has served as a suitable starting point for a thorough investigation of positions 8 and 2. While position 8 of the purine scaffold can only bear a small substituent to maintain the inhibitory activity, position 2 is opened for extensive modification and can accommodate even substituted phenyl rings without the loss of PI4K III beta inhibitory activity. These empirical observations nicely correlate with the results of our docking study, which suggests that position 2 directs towards solution and can provide the necessary space for the interaction with remote residues of the enzyme, whereas the cavity around position 8 is strictly limited. The obtained compounds have also been subjected to antiviral screening against a panel of (+) ssRNA viruses.

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

2016

Kód důvěrnosti údajů

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

Název periodika

Bioorganic and Medicinal Chemistry Letters

ISSN

0960-894X

e-ISSN

—

Svazek periodika

26

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

2706-2712

Kód UT WoS článku

000374988600028

EID výsledku v databázi Scopus

2-s2.0-84963686126