Title

Pyridone-Conjugated Monobactam Antibiotics with Gram-Negative Activity

Document Type

Article

Publication Date

2013

Publication Title

Journal of Medicinal Chemistry

Volume Number

56

Issue Number

13

DOI

10.1021/jm400560z

Abstract

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.

ISSN

0022-2623

First Page

5541

Last Page

5552

Link Out URL

https://doi.org/10.1021/jm400560z

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