作者
Matthew F. Brown,Mark J. Mitton‐Fry,Joel T. Arcari,Rose A. Barham,Jeffrey Casavant,Brian S. Gerstenberger,Seungil Han,Joel R. Hardink,Thomas M. Harris,Thuy Hoang,Michael D. Huband,Manjinder S. Lall,M. Megan Lemmon,Chao Li,Jian Lin,Sandra P. McCurdy,Eric B. McElroy,Craig J. McPherson,Eric S. Marr,John P. Mueller,Lisa Mullins,A. A. Nikitenko,Mark C. Noe,Joseph Penzien,Mark S. Plummer,Brandon P. Schuff,Veerabahu Shanmugasundaram,Jeremy T. Starr,Jianmin Sun,Andrew P. Tomaras,Jennifer A. Young,Richard P. Zaniewski
摘要
Herein we describe the structure-aided design and synthesis of a series of pyridone-conjugated monobactam analogues with in vitro antibacterial activity against clinically relevant Gram-negative species including Pseudomonas aeruginosa , Klebsiella pneumoniae , and Escherichia coli . Rat pharmacokinetic studies with compound 17 demonstrate low clearance and low plasma protein binding. In addition, evidence is provided for a number of analogues suggesting that the siderophore receptors PiuA and PirA play a role in drug uptake in P. aeruginosa strain PAO1.