292619-97-7Relevant academic research and scientific papers
Synthesis of substituted 6-anilinouracils and their inhibition of DNA polymerase IIIC and gram-positive bacterial growth
Zhi, Chengxin,Long, Zheng-Yu,Gambino, Joseph,Xu, Wei-Chu,Brown, Neal C.,Barnes, Marjorie,Butler, Michelle,LaMarr, William,Wright, George E.
, p. 2731 - 2739 (2007/10/03)
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.
