Journal of Medicinal Chemistry p. 5541 - 5552 (2013)
Update date:2022-08-04
Topics: Activity Experimental Antibiotics Pyridone-conjugated Monobactam Gram-negative
Brown, Matthew F.
Mitton-Fry, Mark J.
Arcari, Joel T.
Barham, Rose
Casavant, Jeffrey
Gerstenberger, Brian S.
Han, Seungil
Hardink, Joel R.
Harris, Thomas M.
Hoang, Thuy
Huband, Michael D.
Lall, Manjinder S.
Lemmon, M. Megan
Li, Chao
Lin, Jian
McCurdy, Sandra P.
McElroy, Eric
McPherson, Craig
Marr, Eric S.
Mueller, John P.
Mullins, Lisa
Nikitenko, Antonia A.
Noe, Mark C.
Penzien, Joseph
Plummer, Mark S.
Schuff, Brandon P.
Shanmugasundaram, Veerabahu
Starr, Jeremy T.
Sun, Jianmin
Tomaras, Andrew
Young, Jennifer A.
Zaniewski, Richard P.
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.
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