| Literature DB >> 23968823 |
Timothy J Miles1, Alan J Hennessy, Ben Bax, Gerald Brooks, Barry S Brown, Pamela Brown, Nathalie Cailleau, Dongzhao Chen, Steven Dabbs, David T Davies, Joel M Esken, Ilaria Giordano, Jennifer L Hoover, Jianzhong Huang, Graham E Jones, Senthill K Kusalakumari Sukmar, Claus Spitzfaden, Roger E Markwell, Elisabeth A Minthorn, Steve Rittenhouse, Michael N Gwynn, Neil D Pearson.
Abstract
During the course of our research to find novel mode of action antibacterials, we discovered a series of hydroxyl tricyclic compounds that showed good potency against Gram-positive and Gram-negative pathogens. These compounds inhibit bacterial type IIA topoisomerases. Herein we will discuss structure-activity relationships in this series and report advanced studies on compound 1 (GSK966587) which demonstrates good PK and in vivo efficacy properties. X-ray crystallographic studies were used to provide insight into the structural basis for the difference in antibacterial potency between enantiomers.Entities:
Keywords: Antibacterials; Bacterial type IIA topoisomerase; Hydroxyl tricyclics; In vivo efficacy; Pharmacokinetic
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Year: 2013 PMID： 23968823 DOI： 10.1016/j.bmcl.2013.07.013
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823