Hybrid antibacterials. DNA polymerase-topoisomerase inhibitors

C Zhi, Z Long, A Manikowski, J Comstock…

Index: Zhi, Chengxin; Long, Zheng-Yu; Manikowski, Andrzej; Comstock, Jeanne; Xu, Wei-Chu; Brown, Neal C.; Tarantino Jr., Paul M.; Holm, Karsten A.; Dix, Edward J.; Wright, George E.; Barnes, Marjorie H.; Butler, Michelle M.; Foster, Kimberly A.; LaMarr, William A.; Bachand, Benoit; Bethell, Richard; Cadilhac, Caroline; Charron, Sylvie; Lamothe, Serge; Motorina, Irina; Storer, Richard Journal of Medicinal Chemistry, 2006 , vol. 49, # 4 p. 1455 - 1465

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Citation Number: 46

Abstract

Novel Gram-positive (Gram+) antibacterial compounds consisting of a DNA polymerase IIIC (pol IIIC) inhibitor covalently connected to a topoisomerase/gyrase inhibitor are described. Specifically, 3-substituted 6-(3-ethyl-4-methylanilino) uracils (EMAUs) in which the 3- substituent is a fluoroquinolone moiety (FQ) connected by various linkers were synthesized. The resulting “AU-FQ” hybrid compounds were significantly more potent than the parent ...