The development of a novel intermolecular oxidative amination reaction, a synthetic transformation that involves the simultaneous functionalization of both an N-H and C-H bond, is described. The process, which is mediated by an I(III) oxidant and contains no metal catalysts, provides a rapid and green method for synthesizing protected anilines from simple arenes and phthalimide. Mechanistic investigations indicate that the reaction proceeds via nucleophilic attack of the phthalimide on an aromatic radical cation, as opposed to the electrophilic aromatic amination that has been reported for other I(III) amination reactions. The application of this new reaction to the synthesis of a variety of substituted aniline derivatives is demonstrated.

The synthesis and biological activity of a new series of LpxC inhibitors represented by pyridone methylsulfone hydroxamate 2a is presented. Members of this series have improved solubility and free fraction when compared to compounds in the previously described biphenyl methylsulfone hydroxamate series, and they maintain superior Gram-negative antibacterial activity to comparator agents.

In this paper, we present the synthesis and SAR as well as selectivity, pharmacokinetic, and infection model data for representative analogues of a novel series of potent antibacterial LpxC inhibitors represented by hydroxamic acid.

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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