Diseases of the Developing World CEDD, GlaxoSmithKline, Madrid, Spain.
Bioorg Med Chem Lett. 2013 Oct 1;23(19):5437-41. doi: 10.1016/j.bmcl.2013.07.013. Epub 2013 Jul 17.
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.
在我们寻找新型作用模式抗菌药物的研究过程中，发现了一系列具有良好抗革兰氏阳性和革兰氏阴性病原体活性的羟基三环类化合物。这些化合物抑制细菌 IIA 拓扑异构酶。本文将讨论该系列化合物的构效关系，并报告化合物 1（GSK966587）的深入研究结果，该化合物具有良好的 PK 和体内疗效性质。X 射线晶体学研究用于深入了解对映体之间抗菌效力差异的结构基础。
