5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F14%3A00432303" target="_blank" >RIV/61388963:_____/14:00432303 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378041:_____/14:00432303 RIV/00216208:11140/14:10296018

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s00044-014-1018-9" target="_blank" >http://dx.doi.org/10.1007/s00044-014-1018-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00044-014-1018-9" target="_blank" >10.1007/s00044-014-1018-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production

Popis výsledku v původním jazyce

A series of 5-substituted 2-amino-4,6-dihydroxypyrimidines were prepared by a modified condensation of the corresponding monosubstituted malonic acid diesters with guanidine in an excess of sodium ethoxide. The optimized procedure using Vilsmeier-Haack-Arnold reagent, followed by immediate deprotection of the (dimethylamino)methylene protecting groups, has been developed to convert the 2-amino-4,6-dihydroxypyrimidine analogs to novel 5-substituted 2-amino-4,6-dichloropyrimidines in high yields. Pilot screening for biological properties of the prepared compounds was done in mouse peritoneal cells using the in vitro nitric oxide (NO) assay. Irrespective of the substituent at the 5 position, 2-amino-4,6-dichloropyrimidines inhibited immune-activated NO production. The most effective was 5-fluoro-2-amino-4,6-dichloropyrimidine with an IC (50) of 2 A mu M (higher activity than the most potent reference compound) while the IC (50)s of other derivatives were within the range of 9-36 A mu M. T

Název v anglickém jazyce

5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production

Popis výsledku anglicky

A series of 5-substituted 2-amino-4,6-dihydroxypyrimidines were prepared by a modified condensation of the corresponding monosubstituted malonic acid diesters with guanidine in an excess of sodium ethoxide. The optimized procedure using Vilsmeier-Haack-Arnold reagent, followed by immediate deprotection of the (dimethylamino)methylene protecting groups, has been developed to convert the 2-amino-4,6-dihydroxypyrimidine analogs to novel 5-substituted 2-amino-4,6-dichloropyrimidines in high yields. Pilot screening for biological properties of the prepared compounds was done in mouse peritoneal cells using the in vitro nitric oxide (NO) assay. Irrespective of the substituent at the 5 position, 2-amino-4,6-dichloropyrimidines inhibited immune-activated NO production. The most effective was 5-fluoro-2-amino-4,6-dichloropyrimidine with an IC (50) of 2 A mu M (higher activity than the most potent reference compound) while the IC (50)s of other derivatives were within the range of 9-36 A mu M. T

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

<a href="/cs/project/GAP303%2F12%2F0172" target="_blank" >GAP303/12/0172: Studie vztahu mezi strukturou a imunosupresivní aktivitou pyrimidinových analogů</a><br>

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

Medicinal Chemistry Research

ISSN

1054-2523

e-ISSN

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Svazek periodika

23

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

4482-4490

Kód UT WoS článku

000341091300018

EID výsledku v databázi Scopus

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