Carbapenem-resistant Enterobacteriaceae (CRE), due to the Klebsiella pneumoniae carbapenemase (KPC) and other β-lactamases, now threatens the usefulness of all β-lactam antibiotics. Boronic acids offered an intriguing group to mimic the transition state of the lactamases and were already known. The research took a highly modern approach of modelling possibilities and generated a new series with a novel cyclic boronic acid. In this manner very few compounds were actually made and profiled – a great example of a highly rationale approach and modern molecular modelling.
Vaborbactam – Discovery of a Cyclic Boronic Acid β-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases.
J. Med. Chem. 2015, 58, 9, 3682–3692
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