Polysubstituted 4,6-bis(hetero)arylpyrimidines as dual inhibitors of nitric oxide and prostaglandin E-2 production

Kód výsledku v IS VaVaI

RIV/61388963:_____/17:00476117 - isvavai.cz

Nalezeny alternativní kódy

RIV/68378041:_____/17:00476117

Výsledek na webu

http://dx.doi.org/10.1016/j.niox.2017.05.001

DOI - Digital Object Identifier

10.1016/j.niox.2017.05.001

Jazyk výsledku

angličtina

Název v původním jazyce

Polysubstituted 4,6-bis(hetero)arylpyrimidines as dual inhibitors of nitric oxide and prostaglandin E-2 production

Popis výsledku v původním jazyce

As a part of our extensive structure -activity relationship study of anti-inflammatory heterocycles, a novel series of 67 polysubstituted 2-aminopyrimidines was prepared bearing one (at the C-4 position of the pyrimidine ring) or two (in the C-4 and C-6 positions) (hetero)aryl substituents attached directly through the C-C bond. The key synthetic steps involved either Suzuki-Miyaura or Stille cross-coupling reactions carried out on easily available 4,6-dichloropyrimidines. All prepared compounds, except one, were able to inhibit immune-activated production of nitric oxide (NO) significantly. Moreover, several compounds were found to be low micromolar dual inhibitors of NO and prostaglandin E-2 (PGE(2)) production. Although the exact mode of action of the prepared compounds remains to be elucidated, non-toxic dual inhibitors of NO and PGE2 production may have great therapeutic benefit in treatment of various inflammation diseases and deserve further preclinical evaluation.

Název v anglickém jazyce

Polysubstituted 4,6-bis(hetero)arylpyrimidines as dual inhibitors of nitric oxide and prostaglandin E-2 production

Popis výsledku anglicky

As a part of our extensive structure -activity relationship study of anti-inflammatory heterocycles, a novel series of 67 polysubstituted 2-aminopyrimidines was prepared bearing one (at the C-4 position of the pyrimidine ring) or two (in the C-4 and C-6 positions) (hetero)aryl substituents attached directly through the C-C bond. The key synthetic steps involved either Suzuki-Miyaura or Stille cross-coupling reactions carried out on easily available 4,6-dichloropyrimidines. All prepared compounds, except one, were able to inhibit immune-activated production of nitric oxide (NO) significantly. Moreover, several compounds were found to be low micromolar dual inhibitors of NO and prostaglandin E-2 (PGE(2)) production. Although the exact mode of action of the prepared compounds remains to be elucidated, non-toxic dual inhibitors of NO and PGE2 production may have great therapeutic benefit in treatment of various inflammation diseases and deserve further preclinical evaluation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

TE01020028: Centrum vývoje originálních léčiv

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Nitric Oxide-Biology and Chemistry

ISSN

1089-8603

e-ISSN

—

Svazek periodika

67

Číslo periodika v rámci svazku

Jul 1

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

5

Strana od-do

53-57

Kód UT WoS článku

000402849600006

EID výsledku v databázi Scopus

2-s2.0-85018785198