Synthesis of substituted 6-anilinouracils and their inhibition of DNA polymerase IIIC and Gram-positive bacterial growth.
J Med Chem
; 46(13): 2731-9, 2003 Jun 19.
Article
em En
| MEDLINE
| ID: mdl-12801236
ABSTRACT
Certain substituted 6-anilinouracils are potent and selective inhibitors of Gram+ bacterial DNA polymerase IIIC (pol IIIC). In addition, analogues with 3-substituents in the uracil ring have potent antibacterial activity against Gram+ organisms in culture. In an attempt to find optimal anilino substituents for pol IIIC binding and optimal 3-substituents for antibacterial activity, we have prepared several series of 3-substituted-6-aminouracils and assayed their activity against pol IIIC from Bacillus subtilis and a panel of Gram+ and Gram- bacteria in culture. The 6-(3-ethyl-4-methylanilino) group and closely related substituent patterns maximized pol IIIC inhibition potency. Among a series of 3-(substituted-butyl)-6-(3-ethyl-4-methylanilino)uracils, basic amino substituents increased pol IIIC inhibition, but decreased antibacterial activity. The most potent antibacterials were simple hydroxybutyl and methoxybutyl derivatives, and hydrophobically substituted piperidinylbutyl derivatives.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Uracila
/
DNA Polimerase III
/
Inibidores Enzimáticos
/
Bactérias Gram-Positivas
/
Compostos de Anilina
/
Antibacterianos
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article