Influence of the C-5 substitution in polysubstituted pyrimidines on inhibition of prostaglandin E2 production

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00493581" target="_blank" >RIV/61388963:_____/18:00493581 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378041:_____/18:00493581

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.ejmech.2018.07.010" target="_blank" >http://dx.doi.org/10.1016/j.ejmech.2018.07.010</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2018.07.010" target="_blank" >10.1016/j.ejmech.2018.07.010</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Influence of the C-5 substitution in polysubstituted pyrimidines on inhibition of prostaglandin E2 production

Popis výsledku v původním jazyce

As a part of a broader structure-activity relationship study of substituted 2-aminopyrimidines, the influence of the C-5 substitution on inhibition of prostaglandin E2 (PGE2) production was studied. Thirty compounds were prepared starting from the corresponding 2-amino-4,6-dichloropyrimidines using Suzuki cross-coupling. It was shown previously that 2-amino-4,6-dichloropyrimidines with smaller C-5 substituent (hydrogen and methyl) were devoid of significant activity, while 5-butyl derivatives exhibited prominent potency. In this study, on the other hand, both monoaryl- and bisarylpyrimidines were potent inhibitors of PGE2 production regardless the length of the C-5 substituent (hydrogen, methyl, n-butyl). Moreover, the shorter the C-5 substituent the higher potency to inhibit PGE2 production was observed. 2-Amino-4,6-diphenylpyrimidine was the best inhibitor of PGE2 production with IC50 = 3 nM and no cytotoxicity. The most potent inhibitors deserve further preclinical evaluation as potential anti-inflammatory agents.

Název v anglickém jazyce

Influence of the C-5 substitution in polysubstituted pyrimidines on inhibition of prostaglandin E2 production

Popis výsledku anglicky

As a part of a broader structure-activity relationship study of substituted 2-aminopyrimidines, the influence of the C-5 substitution on inhibition of prostaglandin E2 (PGE2) production was studied. Thirty compounds were prepared starting from the corresponding 2-amino-4,6-dichloropyrimidines using Suzuki cross-coupling. It was shown previously that 2-amino-4,6-dichloropyrimidines with smaller C-5 substituent (hydrogen and methyl) were devoid of significant activity, while 5-butyl derivatives exhibited prominent potency. In this study, on the other hand, both monoaryl- and bisarylpyrimidines were potent inhibitors of PGE2 production regardless the length of the C-5 substituent (hydrogen, methyl, n-butyl). Moreover, the shorter the C-5 substituent the higher potency to inhibit PGE2 production was observed. 2-Amino-4,6-diphenylpyrimidine was the best inhibitor of PGE2 production with IC50 = 3 nM and no cytotoxicity. The most potent inhibitors deserve further preclinical evaluation as potential anti-inflammatory agents.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/TE01020028" target="_blank" >TE01020028: Centrum vývoje originálních léčiv</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

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

—

Svazek periodika

156

Číslo periodika v rámci svazku

Aug 5

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

7

Strana od-do

295-301

Kód UT WoS článku

000443663200023

EID výsledku v databázi Scopus

2-s2.0-85049555802